ASTEROID: A Study in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With BPS804
Sponsor
Ultragenyx Pharmaceutical Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT03118570
Collaborator
Mereo BioPharma (Industry)
112
25
5
38
4.5
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to select a suitable dose of BPS804 by measuring the strength/quality of bone using a special type of CT scanner. Participants will be treated for 12 months and followed up for a further 12 months.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This study was previously posted by Mereo Biopharma and was transferred to Ultragenyx in February 2021.
Study Design
Study Type:
Interventional
Actual Enrollment
:
112 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Double-blind, Dose-finding Study, incorporating an open-label substudyDouble-blind, Dose-finding Study, incorporating an open-label substudy
Masking:
Double (Participant, Investigator)
Masking Description:
Sponsor will be masked until the primary analysis of the study except for open-label substudy treatment arm. The study site pharmacist will be unmasked to treatment allocation throughout. Study treatment will be monitored by a separate unmasked monitoring team.
Primary Purpose:
Treatment
Official Title:
A Phase 2b, Multicentre, Multinational, Double-blind, Dose-finding Study, Incorporating an Open Label Substudy, in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With Setrusumab (BPS804)
Actual Study Start Date
:
Sep 11, 2017
Actual Primary Completion Date
:
Oct 1, 2019
Actual Study Completion Date
:
Nov 12, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Setrusumab 20 mg/kg (Blinded) Setrusumab 20 mg/kg intravenous (IV) infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
Drug: setrusumab
Intravenous infusion
Other Names:
Dietary Supplement: Calcium
tablets
Dietary Supplement: Vitamin D
capsules
Drug: zoledronic acid (optional)
Following completion of the study treatment (Month 12) participants can receive an optional single dose of zoledronic acid. Participants can receive an optional further dose of zoledronic acid at Month 18 at the discretion of their treating physician.
|
| Experimental: Setrusumab 8 mg/kg (Blinded) Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
Drug: setrusumab
Intravenous infusion
Other Names:
Dietary Supplement: Calcium
tablets
Dietary Supplement: Vitamin D
capsules
Drug: zoledronic acid (optional)
Following completion of the study treatment (Month 12) participants can receive an optional single dose of zoledronic acid. Participants can receive an optional further dose of zoledronic acid at Month 18 at the discretion of their treating physician.
|
| Experimental: Setrusumab 2 mg/kg (Blinded) Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
Drug: setrusumab
Intravenous infusion
Other Names:
Dietary Supplement: Calcium
tablets
Dietary Supplement: Vitamin D
capsules
Drug: zoledronic acid (optional)
Following completion of the study treatment (Month 12) participants can receive an optional single dose of zoledronic acid. Participants can receive an optional further dose of zoledronic acid at Month 18 at the discretion of their treating physician.
|
| Experimental: Setrusumab 20 mg/kg (Open-Label) Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
Drug: setrusumab
Intravenous infusion
Other Names:
Dietary Supplement: Calcium
tablets
Dietary Supplement: Vitamin D
capsules
Drug: zoledronic acid (optional)
Following completion of the study treatment (Month 12) participants can receive an optional single dose of zoledronic acid. Participants can receive an optional further dose of zoledronic acid at Month 18 at the discretion of their treating physician.
|
| Placebo Comparator: Placebo Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
Dietary Supplement: Calcium
tablets
Dietary Supplement: Vitamin D
capsules
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12 [Baseline, Month 12 (end of treatment [EOT])]
Assessed by high resolution peripheral quantitative computed tomography (HRpQCT). HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presents the ratio of the means between the visit and Baseline from analysis of covariance (ANCOVA).
- Change From Baseline in Radial Bone Strength (Failure Load) at Month 12 [Baseline, Month 12 (EOT)]
Assessed by finite element analysis (FEA) of models generated from HRpQCT images of the distal radius.
- Change From Baseline in Radial Bone Strength (Stiffness) at Month 12 [Baseline, Month 12 (EOT)]
Assessed by FEA of models generated from HRpQCT images of the distal radius.
Secondary Outcome Measures
- Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set [Baseline, Months 6, 12 (EOT), 18, 24]
Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.
- Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm [Baseline, Months 6, 12 (EOT)]
Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.
- Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set [Baseline, Months 6, 12 (EOT), 18, 24]
Assessed by FEA of models generated from HRpQCT images of the distal radius.
- Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm [Baseline, Months 6, 12 (EOT)]
Assessed by FEA of models generated from HRpQCT images of the distal radius.
- Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set [Baseline, Months 6, 12 (EOT), 18, 24]
Assessed by FEA of models generated from HRpQCT images of the distal radius.
- Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm [Baseline, Months 6, 12 (EOT)]
Assessed by FEA of models generated from HRpQCT images of the distal radius.
- Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 [Month 12 (EOT)]
Fracture assessment, confirmed by central radiographic reading, was carried out for peripheral including all major long bones, minor bone (digits, ribs) and vertebral fractures. Fractures without clinical symptoms, detected only by means of radiographic investigations, were not included in the analysis.
- Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 [Baseline, Month 6]
BMD was evaluated by dual-energy x-ray absorptiometry (DXA). T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD.
- Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 [Baseline, Month 6]
BMD was evaluated by DXA.
- Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 [Baseline, Month 12 (EOT)]
BMD was evaluated by DXA. T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD.
- Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 [Baseline, Month 12 (EOT)]
BMD was evaluated by DXA.
- Change From Baseline in Total vBMD (Radial and Tibial) Over Time [Baseline, Months 6, 12 (EOT), 18, and 24]
Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.
- Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time [Baseline, Months 6, 12 (EOT), 18, and 24]
Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.
- Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set [Baseline, Month 6, Month 12 (EOT)]
- Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 [Baseline, Months 6, 12 (EOT)]
Lean and fat body mass was evaluated using whole body DXA (including the head).
- Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 [Baseline, Months 1, 3, 6, 9, 12 (EOT)]
- Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 [Baseline, Months 1, 3, 6, 9, 12 (EOT)]
- Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12 [Baseline, Months 6, 12 (EOT)]
The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Physical Component Summary ranges from 0 to 100, where higher scores reflect better physical functioning.
- Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12 [Baseline, Months 6, 12 (EOT)]
The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Mental Component Summary ranges from 0 to 100, where higher scores reflect better mental health functioning.
- Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12 [Baseline, Months 6 and 12 (EOT)]
The EQ-5D-5L is a standardised measure of health status comprised of a descriptive system of 5 health-related quality of life states (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a Visual Analogue Scale (VAS) of overall health. Each dimension is rated on a 5-point response scale indicating severity of problems, where 1 is "no problems" and 5 is "extreme problems". The 5 questions are scored and together contribute to the EQ-5D index (utility) score between 0 and 1 (1 being perfect health).
- Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12 [Baseline, Months 6, 12 (EOT)]
The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The total score is calculated on a 0-100 scale, where higher scores indicate a greater (negative) impact on quality of life.
- Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12 [Baseline, Months 6, 12 (EOT)]
The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Pain subscale ranges from 0 to 10, with higher value representing worse pain.
- Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12 [Baseline, Months 6, 12 (EOT)]
The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Activities subscale ranges from 0 to 100, with higher value representing increased difficulty.
- Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 [up to Month 14]
Serum samples were screened for antibodies binding to setrusumab using a validated assay method by or under the supervision of the sponsor.
- Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death [Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.)]
An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; is another important medical event. The intensity for each AE was graded as mild, moderate or severe, according to the investigator's judgement. An event was considered related to study drug if there were a "reasonable possibility" of a relationship, according to the investigator's clinical judgment. A TEAE was defined as an event occurring or worsening on or after the first dose of study medication.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients with a clinical diagnosis of OI Type I, III or IV with a confirmed defect in the COL1A1/COL1A2 genes, as confirmed by genetic testing
-
One or more fractures in the past 5 years
-
Capable of giving signed consent
Exclusion Criteria:
-
History of skeletal malignancies or other bone diseases (other than OI)
-
History of neural foraminal stenosis (except if due to scoliosis)
-
History of myocardial infarction, angina pectoris, ischaemic stroke or transient ischaemic attack
-
History of endocrine or thyroid/parathyroid conditions that could affect bone metabolism
-
Treatment with bisphosphonates within 3 months of randomisation
-
Treatment with teraparatide, denosumab or other anabolic/anti-reabsorptive medications within 6 months of randomisation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mereo Investigator Site | Birmingham | Alabama | United States | 35294 |
| 2 | Mereo Investigator Site | Jacksonville | Florida | United States | 32207 |
| 3 | Mereo Investigator Site | Baltimore | Maryland | United States | 21287 |
| 4 | Mereo Investigator Site | Boston | Massachusetts | United States | 012115 |
| 5 | Mereo Investigator Site | Saint Paul | Minnesota | United States | 55101 |
| 6 | Mereo Investigator Site | Saint Louis | Missouri | United States | 63110 |
| 7 | Mereo Investigator Site | Albuquerque | New Mexico | United States | 87106 |
| 8 | Mereo Investigator Site | Cincinnati | Ohio | United States | 45229 |
| 9 | Mereo Investigator Site | Portland | Oregon | United States | 97239 |
| 10 | Mereo Investigator Site | Pittsburgh | Pennsylvania | United States | 15225 |
| 11 | Mereo Investigator Site | Nashville | Tennessee | United States | 37232 |
| 12 | Mereo Investigator Site | Houston | Texas | United States | 77030 |
| 13 | Mereo Investigator Site | Toronto | Ontario | Canada | |
| 14 | Mereo Investigator Site | Montreal | Quebec | Canada | |
| 15 | Mereo Investigator Site | Quebec City | Quebec | Canada | |
| 16 | Mereo Investigator Site | Aarhus | Denmark | ||
| 17 | Mereo Investigator Site | Odense | Denmark | ||
| 18 | Mereo Investigator Site | Paris | Paris Cedex 14 | France | |
| 19 | Mereo Investigator Site | Lyon | France | ||
| 20 | Mereo Investigator Site | Paris | France | ||
| 21 | Mereo Investigator Site | Cambridge | Cambridgeshire | United Kingdom | |
| 22 | Mereo Investigator Site | Newcastle upon Tyne | Newcastle | United Kingdom | |
| 23 | Mereo Investigator Site | Oxford | Oxfordshire | United Kingdom | |
| 24 | Mereo Investigator Site | Bristol | United Kingdom | ||
| 25 | Mereo Investigator Site | London | United Kingdom |
Sponsors and Collaborators
- Ultragenyx Pharmaceutical Inc
- Mereo BioPharma
Investigators
- Study Director: Medical Director, Mereo BioPharma
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier:
NCT03118570
Other Study ID Numbers:
- MBPS205
- 2016-005096-27
First Posted:
Apr 18, 2017
Last Update Posted:
Mar 2, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Ultragenyx Pharmaceutical Inc
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Participants were randomized 1:1:1:1 to 3 doses of setrusumab (20 mg/kg, 8 mg/kg and 2 mg/kg) and placebo for a 12-month Treatment Period. Per Protocol Amendment 4, participants originally randomized to the placebo group were reassigned to receive 20 mg/kg open-label setrusumab (1 discontinued study prior to the transition). Two participants in the setrusumab 20 mg/kg open-label group were randomized into this group after Amendment 4 and did not receive placebo. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) | Setrusumab 20 mg/kg (Open-Label) | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg intravenous (IV) infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. Participants were randomized to this group after amendment 4. | Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. Due to a protocol amendment, placebo was actually received for an average of 5 months. Participants originally randomized to the placebo group were reassigned to receive 20 mg/kg open-label setrusumab after amendment 4. |
| Period Title: Overall Study | |||||
| STARTED | 31 | 29 | 30 | 2 | 20 |
| Reassigned From Placebo to 20 mg/kg Open-Label Setrusumab | 0 | 0 | 0 | 0 | 19 |
| COMPLETED | 26 | 22 | 25 | 2 | 15 |
| NOT COMPLETED | 5 | 7 | 5 | 0 | 5 |
Baseline Characteristics
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) | Setrusumab 20 mg/kg (Open-Label) | Placebo | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. Due to a protocol amendment, placebo was actually received for an average of 5 months. | Total of all reporting groups |
| Overall Participants | 31 | 29 | 30 | 2 | 20 | 112 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
40.6
(13.73)
|
40.4
(14.34)
|
47.2
(12.42)
|
43.5
(14.85)
|
40.9
(14.68)
|
42.4
(13.80)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
17
54.8%
|
20
69%
|
21
70%
|
1
50%
|
14
70%
|
73
65.2%
|
| Male |
14
45.2%
|
9
31%
|
9
30%
|
1
50%
|
6
30%
|
39
34.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
3
9.7%
|
1
3.4%
|
2
6.7%
|
0
0%
|
1
5%
|
7
6.3%
|
| Not Hispanic or Latino |
27
87.1%
|
27
93.1%
|
28
93.3%
|
2
100%
|
19
95%
|
103
92%
|
| Unknown or Not Reported |
1
3.2%
|
1
3.4%
|
0
0%
|
0
0%
|
0
0%
|
2
1.8%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||
| Black or African American |
2
6.5%
|
1
3.4%
|
1
3.3%
|
0
0%
|
0
0%
|
4
3.6%
|
| White |
29
93.5%
|
27
93.1%
|
29
96.7%
|
2
100%
|
20
100%
|
107
95.5%
|
| Not Collected or Not Reported |
0
0%
|
1
3.4%
|
0
0%
|
0
0%
|
0
0%
|
1
0.9%
|
Outcome Measures
| Title | Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12 |
|---|---|
| Description | Assessed by high resolution peripheral quantitative computed tomography (HRpQCT). HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presents the ratio of the means between the visit and Baseline from analysis of covariance (ANCOVA). |
| Time Frame | Baseline, Month 12 (end of treatment [EOT]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment (per protocol almost all efficacy endpoints were to be analyzed only in the blinded treatment arms). Participants with an assessment at given time point. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Number (95% Confidence Interval) [ratio] |
1.004
|
0.993
|
0.992
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.644 |
| Comments | Analysis is based on a log transformed analysis of covariance (ANCOVA) model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.485 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.404 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Radial Bone Strength (Failure Load) at Month 12 |
|---|---|
| Description | Assessed by finite element analysis (FEA) of models generated from HRpQCT images of the distal radius. |
| Time Frame | Baseline, Month 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given time point. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 28 | 22 | 25 |
| Least Squares Mean (Standard Error) [newton (N)] |
61.25
(21.669)
|
32.25
(24.342)
|
8.86
(23.200)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.006 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.190 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.704 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Radial Bone Strength (Stiffness) at Month 12 |
|---|---|
| Description | Assessed by FEA of models generated from HRpQCT images of the distal radius. |
| Time Frame | Baseline, Month 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given time point. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 28 | 22 | 25 |
| Least Squares Mean (Standard Error) [N/mm] |
1638.70
(625.808)
|
1422.00
(703.275)
|
209.89
(671.777)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.011 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.047 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.756 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set |
|---|---|
| Description | Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA. |
| Time Frame | Baseline, Months 6, 12 (EOT), 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given time point. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Radial: Month 6 |
1.007
|
1.000
|
0.998
|
| Radial: Month 12 |
1.004
|
0.993
|
0.992
|
| Radial: Month 18 |
1.002
|
0.992
|
0.979
|
| Radial: Month 24 |
0.997
|
0.998
|
0.979
|
| Tibial: Month 6 |
1.004
|
1.016
|
0.990
|
| Tibial: Month 12 |
0.991
|
1.018
|
0.973
|
| Tibial: Month 18 |
0.989
|
1.042
|
0.983
|
| Tibial: Month 24 |
1.000
|
1.062
|
1.017
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.329 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.953 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.795 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.644 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.485 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.404 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.827 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.459 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.022 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.821 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.911 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.152 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.668 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.109 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.358 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.742 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.567 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.430 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.634 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.146 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.521 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.991 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.069 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.625 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm |
|---|---|
| Description | Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA. |
| Time Frame | Baseline, Months 6, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in the open-label arm who took at least 1 dose of study treatment. Participants with an assessment at given time point. |
| Arm/Group Title | Setrusumab 20 mg/kg (Open-Label) |
|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 21 |
| Radial: Month 6 |
0.994
|
| Radial: Month 12 |
1.011
|
| Tibial: Month 6 |
1.013
|
| Tibial: Month 12 |
1.035
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.615 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.376 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.259 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.253 |
| Comments | Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set |
|---|---|
| Description | Assessed by FEA of models generated from HRpQCT images of the distal radius. |
| Time Frame | Baseline, Months 6, 12 (EOT), 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given time point. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Radial: Month 6 |
31.22
|
39.95
|
-3.28
|
| Radial: Month 12 |
61.25
|
32.25
|
8.86
|
| Radial: Month 18 |
50.39
|
43.11
|
-10.53
|
| Radial: Month 24 |
-19.59
|
45.03
|
-50.65
|
| Tibial: Month 6 |
46.00
|
45.91
|
-65.33
|
| Tibial: Month 12 |
76.15
|
60.20
|
-65.96
|
| Tibial: Month 18 |
50.69
|
88.33
|
-49.50
|
| Tibial: Month 24 |
-24.75
|
41.37
|
-74.94
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.064 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.019 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.845 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.006 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.190 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.704 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.021 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.504 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.462 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.134 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.086 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.199 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 8 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.219 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.112 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.086 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.245 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.232 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.237 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.088 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.302 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.626 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 8 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.517 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.262 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm |
|---|---|
| Description | Assessed by FEA of models generated from HRpQCT images of the distal radius. |
| Time Frame | Baseline, Months 6, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in the open-label arm who took at least 1 dose of study treatment. Participants with an assessment at given time point. |
| Arm/Group Title | Setrusumab 20 mg/kg (Open-Label) |
|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 21 |
| Radial: Month 6 |
110.16
|
| Radial: Month 12 |
88.32
|
| Tibial: Month 6 |
69.78
|
| Tibial: Month 12 |
112.92
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.080 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.031 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set |
|---|---|
| Description | Assessed by FEA of models generated from HRpQCT images of the distal radius. |
| Time Frame | Baseline, Months 6, 12 (EOT), 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given time point. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Radial: Month 6 |
795.67
|
1048.61
|
109.65
|
| Radial: Month 12 |
1638.70
|
1422.00
|
209.89
|
| Radial: Month 18 |
1295.98
|
803.50
|
-215.92
|
| Radial: Month 24 |
-625.46
|
1172.45
|
-1258.55
|
| Tibial: Month 6 |
1344.84
|
1051.40
|
-1356.71
|
| Tibial: Month 12 |
2326.63
|
1543.85
|
-1428.87
|
| Tibial: Month 18 |
1047.16
|
1697.21
|
-815.38
|
| Tibial: Month 24 |
-1250.69
|
622.77
|
-1844.84
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.060 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.015 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.795 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.011 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.047 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.756 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.006 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.137 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.639 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.325 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.108 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.078 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.106 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.236 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.164 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.031 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.224 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.291 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.324 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.188 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.503 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.385 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.727 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.338 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm |
|---|---|
| Description | Assessed by FEA of models generated from HRpQCT images of the distal radius. |
| Time Frame | Baseline, Months 6, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in the open-label arm who took at least 1 dose of study treatment. Participants with an assessment at given time point. |
| Arm/Group Title | Setrusumab 20 mg/kg (Open-Label) |
|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 21 |
| Radial: Month 6 |
5056.51
|
| Radial: Month 12 |
4992.82
|
| Tibial: Month 6 |
4225.92
|
| Tibial: Month 12 |
5827.81
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12 |
|---|---|
| Description | Fracture assessment, confirmed by central radiographic reading, was carried out for peripheral including all major long bones, minor bone (digits, ribs) and vertebral fractures. Fractures without clinical symptoms, detected only by means of radiographic investigations, were not included in the analysis. |
| Time Frame | Month 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Peripheral |
6.5
21%
|
17.2
59.3%
|
13.3
44.3%
|
| Vertebral |
0
0%
|
0
0%
|
0
0%
|
| Long-Bone |
3.2
10.3%
|
13.8
47.6%
|
3.3
11%
|
| Any |
16.1
51.9%
|
34.5
119%
|
23.3
77.7%
|
| Title | Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6 |
|---|---|
| Description | BMD was evaluated by dual-energy x-ray absorptiometry (DXA). T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD. |
| Time Frame | Baseline, Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Lumbar |
0.273
|
0.338
|
0.110
|
| Total Body |
0.072
|
0.071
|
0.122
|
| Femoral Neck |
-0.024
|
0.102
|
0.087
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.080 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.238 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.238 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.035 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.687 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.107 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.128 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6 |
|---|---|
| Description | BMD was evaluated by DXA. |
| Time Frame | Baseline, Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Lumbar |
4.06
|
4.70
|
1.58
|
| Total Body |
0.77
|
0.83
|
1.21
|
| Femoral Neck |
-0.42
|
1.64
|
1.61
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.088 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.184 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.144 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.028 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.694 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.143 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.111 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12 |
|---|---|
| Description | BMD was evaluated by DXA. T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD. |
| Time Frame | Baseline, Month 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Lumbar |
0.587
|
0.486
|
0.174
|
| Total Body |
0.181
|
0.199
|
0.108
|
| Femoral Neck |
0.163
|
0.159
|
0.104
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.026 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.007 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.085 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.040 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.061 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.189 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12 |
|---|---|
| Description | BMD was evaluated by DXA. |
| Time Frame | Baseline, Month 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Lumbar |
8.55
|
6.79
|
2.50
|
| Total Body |
1.98
|
2.03
|
1.06
|
| Femoral Neck |
3.30
|
2.65
|
1.90
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Lumbar | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.035 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Total body | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.088 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.016 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.068 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Femoral neck | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.160 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Total vBMD (Radial and Tibial) Over Time |
|---|---|
| Description | Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA. |
| Time Frame | Baseline, Months 6, 12 (EOT), 18, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Radial, Month 6 |
1.011
|
0.995
|
1.000
|
| Radial, Month 12 |
1.017
|
1.008
|
0.999
|
| Radial, Month 18 |
1.013
|
0.992
|
0.996
|
| Radial, Month 24 |
0.998
|
1.009
|
0.985
|
| Tibial, Month 6 |
1.017
|
1.011
|
0.995
|
| Tibial, Month 12 |
1.024
|
1.011
|
0.989
|
| Tibial, Month 18 |
1.020
|
1.021
|
0.987
|
| Tibial, Month 24 |
1.001
|
1.025
|
0.994
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.065 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.405 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.966 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.229 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.807 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.042 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.283 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.536 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.765 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.247 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.050 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.037 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.174 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.558 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.020 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.346 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.387 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.093 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.156 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.324 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.920 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.040 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.643 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time |
|---|---|
| Description | Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA. |
| Time Frame | Baseline, Months 6, 12 (EOT), 18, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Radial, Month 6 |
1.004
|
1.002
|
0.998
|
| Radial, Month 12 |
1.005
|
1.003
|
1.001
|
| Radial, Month 18 |
1.011
|
1.001
|
1.007
|
| Radial, Month 24 |
1.011
|
1.018
|
1.002
|
| Tibial, Month 6 |
1.012
|
0.997
|
0.998
|
| Tibial, Month 12 |
1.017
|
1.004
|
0.998
|
| Tibial, Month 18 |
1.024
|
1.004
|
0.993
|
| Tibial, Month 24 |
1.020
|
1.017
|
0.996
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.285 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.544 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.615 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.179 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.513 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.849 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.037 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.880 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.153 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.073 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.007 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Radial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.791 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.010 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.553 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.652 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.482 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.685 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.672 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 18 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.377 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.015 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.086 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Tibial, Month 24 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.712 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set |
|---|---|
| Description | |
| Time Frame | Baseline, Month 6, Month 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Month 6: Body Height |
0
0%
|
0
0%
|
0
0%
|
| Month 6: Weight |
0
0%
|
0
0%
|
0
0%
|
| Month 6: BMI |
0
0%
|
0
0%
|
0
0%
|
| Month 12: Body Height |
0
0%
|
0
0%
|
0
0%
|
| Month 12: Weight |
0
0%
|
0
0%
|
0
0%
|
| Month 12: BMI |
0
0%
|
0
0%
|
0
0%
|
| Title | Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12 |
|---|---|
| Description | Lean and fat body mass was evaluated using whole body DXA (including the head). |
| Time Frame | Baseline, Months 6, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Month 6: Lean |
519.152
|
-410.664
|
168.206
|
| Month 12: Lean |
867.668
|
-225.474
|
184.164
|
| Month 6: Fat |
42.567
|
105.420
|
426.388
|
| Month 12: Fat |
421.266
|
-85.495
|
792.485
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Lean, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.045 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Lean, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.101 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Lean, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.482 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Lean, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.011 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Lean, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.508 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Lean, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.563 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Fat, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.917 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Fat, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.789 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Fat, Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.262 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Fat, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.426 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Fat, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.871 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Fat, Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.113 |
| Comments | Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12 |
|---|---|
| Description | |
| Time Frame | Baseline, Months 1, 3, 6, 9, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Month 1 |
24.349
|
14.288
|
0.060
|
| Month 3 |
17.903
|
6.735
|
0.640
|
| Month 6 |
13.096
|
6.665
|
-0.429
|
| Month 9 |
7.265
|
0.238
|
-2.254
|
| Month 12 |
5.452
|
4.172
|
4.428
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 1 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 1 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 1 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.984 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 3 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 3 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.050 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 3 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.857 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.079 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.912 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 9 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.054 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 9 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.950 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 9 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.555 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.221 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.393 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.385 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12 |
|---|---|
| Description | |
| Time Frame | Baseline, Months 1, 3, 6, 9, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Month 1 |
-0.077
|
-0.047
|
-0.041
|
| Month 3 |
-0.044
|
-0.029
|
-0.043
|
| Month 6 |
-0.013
|
-0.025
|
-0.028
|
| Month 9 |
-0.020
|
-0.039
|
-0.031
|
| Month 12 |
-0.037
|
-0.002
|
-0.034
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 1 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 1 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 1 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 3 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 3 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.050 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 3 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.006 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.519 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.226 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.190 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 9 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.388 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 9 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.109 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 9 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.204 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.119 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.925 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.204 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12 |
|---|---|
| Description | The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Physical Component Summary ranges from 0 to 100, where higher scores reflect better physical functioning. |
| Time Frame | Baseline, Months 6, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Month 6 |
0.672
|
-0.463
|
1.342
|
| Month 12 |
-1.178
|
-0.994
|
2.171
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.588 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.697 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.283 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.354 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.430 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.091 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12 |
|---|---|
| Description | The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Mental Component Summary ranges from 0 to 100, where higher scores reflect better mental health functioning. |
| Time Frame | Baseline, Months 6, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Month 6 |
0.966
|
-0.492
|
-1.133
|
| Month 12 |
2.807
|
-1.473
|
-1.664
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.527 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.738 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.465 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.068 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.328 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.277 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12 |
|---|---|
| Description | The EQ-5D-5L is a standardised measure of health status comprised of a descriptive system of 5 health-related quality of life states (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a Visual Analogue Scale (VAS) of overall health. Each dimension is rated on a 5-point response scale indicating severity of problems, where 1 is "no problems" and 5 is "extreme problems". The 5 questions are scored and together contribute to the EQ-5D index (utility) score between 0 and 1 (1 being perfect health). |
| Time Frame | Baseline, Months 6 and 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Month 6 |
0.0627
|
0.0362
|
-0.0383
|
| Month 12 |
0.0424
|
0.0252
|
0.0214
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.092 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.310 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.304 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.155 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.392 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.464 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12 |
|---|---|
| Description | The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The total score is calculated on a 0-100 scale, where higher scores indicate a greater (negative) impact on quality of life. |
| Time Frame | Baseline, Months 6, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Month 6 |
-3.584
|
-1.848
|
-0.649
|
| Month 12 |
-1.668
|
-0.587
|
-3.846
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.150 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.468 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.800 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.563 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.839 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.186 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12 |
|---|---|
| Description | The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Pain subscale ranges from 0 to 10, with higher value representing worse pain. |
| Time Frame | Baseline, Months 6, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Month 6 |
-3.990
|
-3.906
|
-6.003
|
| Month 12 |
-3.655
|
-4.968
|
-7.178
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.278 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.292 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.115 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.356 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.205 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.078 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12 |
|---|---|
| Description | The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Activities subscale ranges from 0 to 100, with higher value representing increased difficulty. |
| Time Frame | Baseline, Months 6, 12 (EOT) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who are randomized to one of the blinded treatment arms and took at least 1 dose of study treatment. Participants with an assessment at given timepoint. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. |
| Measure Participants | 31 | 29 | 30 |
| Month 6 |
-5.980
|
-2.722
|
1.907
|
| Month 12 |
-0.964
|
4.489
|
-1.630
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.037 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.342 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 6 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.515 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 20 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.786 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 8 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.212 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Setrusumab 2 mg/kg (Blinded) |
|---|---|---|
| Comments | Month 12 | |
| Type of Statistical Test | Superiority | |
| Comments | Comparison is between the Visit and Baseline | |
| Statistical Test of Hypothesis | p-Value | 0.655 |
| Comments | Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14 |
|---|---|
| Description | Serum samples were screened for antibodies binding to setrusumab using a validated assay method by or under the supervision of the sponsor. |
| Time Frame | up to Month 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least 1 dose of study drug. The 19 participants who transitioned from the Placebo arm to the Setrusumab 20 mg/kg Open-Label arm are reflected in both arms for this analysis. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) | Setrusumab 20 mg/kg (Open-Label) | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. Due to a protocol amendment, placebo was actually received for an average of 5 months. |
| Measure Participants | 31 | 29 | 30 | 21 | 20 |
| Binding Antibodies |
16.1
51.9%
|
17.2
59.3%
|
16.7
55.7%
|
9.5
475%
|
15.0
75%
|
| Neutralizing Antibodies |
16.1
51.9%
|
17.2
59.3%
|
16.7
55.7%
|
0
0%
|
0
0%
|
| Both Binding and Neutralizing Antibodies |
16.1
51.9%
|
17.2
59.3%
|
16.7
55.7%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death |
|---|---|
| Description | An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; is another important medical event. The intensity for each AE was graded as mild, moderate or severe, according to the investigator's judgement. An event was considered related to study drug if there were a "reasonable possibility" of a relationship, according to the investigator's clinical judgment. A TEAE was defined as an event occurring or worsening on or after the first dose of study medication. |
| Time Frame | Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least 1 dose of study drug. The 19 participants who transitioned from the Placebo arm to the Setrusumab 20 mg/kg Open-Label arm are reflected in both arms for this analysis. |
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) | Setrusumab 20 mg/kg (Open-Label) | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. Due to a protocol amendment, placebo was actually received for an average of 5 months. |
| Measure Participants | 31 | 29 | 30 | 21 | 20 |
| All AEs |
100.0
322.6%
|
96.6
333.1%
|
90.0
300%
|
100.0
5000%
|
90.0
450%
|
| TEAEs |
100.0
322.6%
|
96.6
333.1%
|
90.0
300%
|
95.2
4760%
|
80.0
400%
|
| Treatment-Related TEAEs |
71.0
229%
|
41.4
142.8%
|
36.7
122.3%
|
42.9
2145%
|
25.0
125%
|
| Serious TEAEs |
12.9
41.6%
|
24.1
83.1%
|
23.3
77.7%
|
23.8
1190%
|
10.0
50%
|
| Treatment-Related Serious TEAEs |
6.5
21%
|
0
0%
|
0
0%
|
9.5
475%
|
0
0%
|
| TEAEs Leading to Death |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| TEAEs Leading to Permanent Study Treatment Discontinuation |
6.5
21%
|
0
0%
|
0
0%
|
9.5
475%
|
5.0
25%
|
Adverse Events
| Time Frame | Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Population: all participants who received at least 1 dose of study drug. The 19 participants who transitioned from the Placebo arm to the Setrusumab 20 mg/kg Open-Label arm are reflected in both arms for this analysis. | |||||||||
| Arm/Group Title | Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) | Setrusumab 20 mg/kg (Open-Label) | Placebo | |||||
| Arm/Group Description | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules. | |||||
All Cause Mortality |
||||||||||
| Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) | Setrusumab 20 mg/kg (Open-Label) | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
Serious Adverse Events |
||||||||||
| Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) | Setrusumab 20 mg/kg (Open-Label) | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/31 (12.9%) | 7/29 (24.1%) | 7/30 (23.3%) | 5/21 (23.8%) | 2/20 (10%) | |||||
| Congenital, familial and genetic disorders | ||||||||||
| Platybasia | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Eye disorders | ||||||||||
| Blindness unilateral | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Visual impairment | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Noninfective sialoadenitis | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Rectal haemorrhage | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| General disorders | ||||||||||
| Chills | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Cholelithiasis | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Immune system disorders | ||||||||||
| Anaphylactic reaction | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Infections and infestations | ||||||||||
| Anal abscess | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Appendicitis | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Device related infection | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Joint abscess | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Pneumonia | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Wound infection | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Pyelonephritis acute | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Femur fracture | 0/31 (0%) | 1/29 (3.4%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Pelvic fracture | 1/31 (3.2%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Tibia fracture | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Ankle fracture | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Fibula fracture | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Fracture of penis | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Hand fracture | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Ilium fracture | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Lumbar vertebral fracture | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Radius fracture | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Rib fracture | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Subcutaneous haematoma | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Wound | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Scapula fracture | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Bone pain | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Fracture nonunion | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Squamous cell carcinoma | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Nervous system disorders | ||||||||||
| Headache | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Hydrocephalus | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Neuritis | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Acute respiratory failure | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Pneumonia aspiration | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Pneumothorax | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Pulmonary hypertension | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Respiratory failure | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Setrusumab 20 mg/kg (Blinded) | Setrusumab 8 mg/kg (Blinded) | Setrusumab 2 mg/kg (Blinded) | Setrusumab 20 mg/kg (Open-Label) | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 29/31 (93.5%) | 28/29 (96.6%) | 27/30 (90%) | 19/21 (90.5%) | 16/20 (80%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 1/31 (3.2%) | 0/29 (0%) | 2/30 (6.7%) | 2/21 (9.5%) | 0/20 (0%) | |||||
| Increased tendency to bruise | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Cardiac disorders | ||||||||||
| Tachycardia | 0/31 (0%) | 0/29 (0%) | 3/30 (10%) | 0/21 (0%) | 0/20 (0%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Ear pain | 0/31 (0%) | 2/29 (6.9%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Middle ear effusion | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Eye disorders | ||||||||||
| Blepharospasm | 2/31 (6.5%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Dental caries | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 1/21 (4.8%) | 1/20 (5%) | |||||
| Diarrhoea | 4/31 (12.9%) | 3/29 (10.3%) | 2/30 (6.7%) | 1/21 (4.8%) | 1/20 (5%) | |||||
| Dyspepsia | 2/31 (6.5%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Gastrooesophageal reflux disease | 1/31 (3.2%) | 2/29 (6.9%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Nausea | 2/31 (6.5%) | 3/29 (10.3%) | 5/30 (16.7%) | 2/21 (9.5%) | 2/20 (10%) | |||||
| Toothache | 2/31 (6.5%) | 0/29 (0%) | 1/30 (3.3%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Vomiting | 3/31 (9.7%) | 1/29 (3.4%) | 1/30 (3.3%) | 3/21 (14.3%) | 1/20 (5%) | |||||
| General disorders | ||||||||||
| Asthenia | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Chest pain | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 2/21 (9.5%) | 0/20 (0%) | |||||
| Fatigue | 3/31 (9.7%) | 2/29 (6.9%) | 7/30 (23.3%) | 3/21 (14.3%) | 0/20 (0%) | |||||
| Influenza like illness | 1/31 (3.2%) | 2/29 (6.9%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Injection site extravasation | 1/31 (3.2%) | 1/29 (3.4%) | 0/30 (0%) | 1/21 (4.8%) | 1/20 (5%) | |||||
| Malaise | 0/31 (0%) | 2/29 (6.9%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Non-cardiac chest pain | 0/31 (0%) | 2/29 (6.9%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Pain | 2/31 (6.5%) | 0/29 (0%) | 2/30 (6.7%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Peripheral swelling | 0/31 (0%) | 2/29 (6.9%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Pyrexia | 1/31 (3.2%) | 2/29 (6.9%) | 2/30 (6.7%) | 2/21 (9.5%) | 2/20 (10%) | |||||
| Immune system disorders | ||||||||||
| Seasonal allergy | 0/31 (0%) | 0/29 (0%) | 2/30 (6.7%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Infections and infestations | ||||||||||
| Bronchitis | 1/31 (3.2%) | 1/29 (3.4%) | 0/30 (0%) | 1/21 (4.8%) | 1/20 (5%) | |||||
| Cystitis | 0/31 (0%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Ear infection | 3/31 (9.7%) | 1/29 (3.4%) | 0/30 (0%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Gastroenteritis | 3/31 (9.7%) | 2/29 (6.9%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Herpes zoster | 2/31 (6.5%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Influenza | 2/31 (6.5%) | 0/29 (0%) | 0/30 (0%) | 4/21 (19%) | 1/20 (5%) | |||||
| Lower respiratory tract infection | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 1/20 (5%) | |||||
| Nasopharyngitis | 5/31 (16.1%) | 3/29 (10.3%) | 4/30 (13.3%) | 5/21 (23.8%) | 3/20 (15%) | |||||
| Sinusitis | 2/31 (6.5%) | 3/29 (10.3%) | 4/30 (13.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Tooth abscess | 0/31 (0%) | 0/29 (0%) | 2/30 (6.7%) | 0/21 (0%) | 0/20 (0%) | |||||
| Upper respiratory tract infection | 1/31 (3.2%) | 0/29 (0%) | 1/30 (3.3%) | 1/21 (4.8%) | 1/20 (5%) | |||||
| Urinary tract infection | 3/31 (9.7%) | 3/29 (10.3%) | 2/30 (6.7%) | 3/21 (14.3%) | 1/20 (5%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Contusion | 1/31 (3.2%) | 2/29 (6.9%) | 1/30 (3.3%) | 3/21 (14.3%) | 0/20 (0%) | |||||
| Fall | 6/31 (19.4%) | 4/29 (13.8%) | 3/30 (10%) | 2/21 (9.5%) | 2/20 (10%) | |||||
| Foot fracture | 3/31 (9.7%) | 4/29 (13.8%) | 3/30 (10%) | 6/21 (28.6%) | 1/20 (5%) | |||||
| Hand fracture | 1/31 (3.2%) | 3/29 (10.3%) | 2/30 (6.7%) | 0/21 (0%) | 0/20 (0%) | |||||
| Infusion related reaction | 4/31 (12.9%) | 3/29 (10.3%) | 1/30 (3.3%) | 2/21 (9.5%) | 0/20 (0%) | |||||
| Joint dislocation | 0/31 (0%) | 0/29 (0%) | 1/30 (3.3%) | 3/21 (14.3%) | 0/20 (0%) | |||||
| Joint injury | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 1/20 (5%) | |||||
| Ligament sprain | 3/31 (9.7%) | 1/29 (3.4%) | 2/30 (6.7%) | 1/21 (4.8%) | 2/20 (10%) | |||||
| Limb injury | 0/31 (0%) | 3/29 (10.3%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Muscle strain | 1/31 (3.2%) | 2/29 (6.9%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Procedural pain | 2/31 (6.5%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Rib fracture | 2/31 (6.5%) | 3/29 (10.3%) | 3/30 (10%) | 0/21 (0%) | 0/20 (0%) | |||||
| Tooth fracture | 3/31 (9.7%) | 2/29 (6.9%) | 6/30 (20%) | 0/21 (0%) | 0/20 (0%) | |||||
| Wound | 0/31 (0%) | 2/29 (6.9%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| Investigations | ||||||||||
| Alanine aminotransferase abnormal | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Alanine aminotransferase increased | 2/31 (6.5%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Aspartate aminotransferase abnormal | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Aspartate aminotransferase increased | 2/31 (6.5%) | 1/29 (3.4%) | 1/30 (3.3%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Blood alkaline phosphatase increased | 2/31 (6.5%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 0/20 (0%) | |||||
| International normalised ratio increased | 0/31 (0%) | 1/29 (3.4%) | 3/30 (10%) | 1/21 (4.8%) | 1/20 (5%) | |||||
| Lipase increased | 1/31 (3.2%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Prothrombin time prolonged | 0/31 (0%) | 1/29 (3.4%) | 3/30 (10%) | 1/21 (4.8%) | 1/20 (5%) | |||||
| Vitamin D decreased | 0/31 (0%) | 1/29 (3.4%) | 2/30 (6.7%) | 2/21 (9.5%) | 0/20 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Hypokalaemia | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 2/21 (9.5%) | 1/20 (5%) | |||||
| Type 2 diabetes mellitus | 0/31 (0%) | 2/29 (6.9%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Vitamin D deficiency | 2/31 (6.5%) | 0/29 (0%) | 1/30 (3.3%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 15/31 (48.4%) | 8/29 (27.6%) | 9/30 (30%) | 8/21 (38.1%) | 5/20 (25%) | |||||
| Back pain | 6/31 (19.4%) | 4/29 (13.8%) | 8/30 (26.7%) | 4/21 (19%) | 1/20 (5%) | |||||
| Bone pain | 4/31 (12.9%) | 3/29 (10.3%) | 4/30 (13.3%) | 2/21 (9.5%) | 0/20 (0%) | |||||
| Muscle spasms | 2/31 (6.5%) | 1/29 (3.4%) | 2/30 (6.7%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Musculoskeletal chest pain | 2/31 (6.5%) | 1/29 (3.4%) | 3/30 (10%) | 2/21 (9.5%) | 0/20 (0%) | |||||
| Musculoskeletal discomfort | 1/31 (3.2%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Myalgia | 2/31 (6.5%) | 1/29 (3.4%) | 0/30 (0%) | 1/21 (4.8%) | 1/20 (5%) | |||||
| Neck pain | 1/31 (3.2%) | 1/29 (3.4%) | 4/30 (13.3%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Pain in extremity | 5/31 (16.1%) | 5/29 (17.2%) | 3/30 (10%) | 4/21 (19%) | 1/20 (5%) | |||||
| Nervous system disorders | ||||||||||
| Dizziness | 2/31 (6.5%) | 0/29 (0%) | 3/30 (10%) | 0/21 (0%) | 1/20 (5%) | |||||
| Headache | 4/31 (12.9%) | 5/29 (17.2%) | 6/30 (20%) | 7/21 (33.3%) | 2/20 (10%) | |||||
| Hypoaesthesia | 3/31 (9.7%) | 0/29 (0%) | 1/30 (3.3%) | 0/21 (0%) | 0/20 (0%) | |||||
| Migraine | 1/31 (3.2%) | 0/29 (0%) | 3/30 (10%) | 0/21 (0%) | 0/20 (0%) | |||||
| Paraesthesia | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Trigeminal neuralgia | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Renal and urinary disorders | ||||||||||
| Nephrolithiasis | 0/31 (0%) | 0/29 (0%) | 2/30 (6.7%) | 1/21 (4.8%) | 0/20 (0%) | |||||
| Renal colic | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Dysmenorrhoea | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 1/21 (4.8%) | 1/20 (5%) | |||||
| Menorrhagia | 0/31 (0%) | 0/29 (0%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 2/31 (6.5%) | 2/29 (6.9%) | 2/30 (6.7%) | 3/21 (14.3%) | 0/20 (0%) | |||||
| Dyspnoea | 0/31 (0%) | 1/29 (3.4%) | 2/30 (6.7%) | 0/21 (0%) | 0/20 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Ecchymosis | 1/31 (3.2%) | 1/29 (3.4%) | 0/30 (0%) | 0/21 (0%) | 1/20 (5%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 1/31 (3.2%) | 0/29 (0%) | 2/30 (6.7%) | 1/21 (4.8%) | 0/20 (0%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Medical Information |
|---|---|
| Organization | Ultragenyx Pharmaceutical Inc |
| Phone | 1-888-756-8567 |
| medinfo@ultragenyx.com |
Responsible Party:
Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier:
NCT03118570
Other Study ID Numbers:
- MBPS205
- 2016-005096-27
First Posted:
Apr 18, 2017
Last Update Posted:
Mar 2, 2022
Last Verified:
Feb 1, 2022