Open-label Extension Denosumab Study in Children and Young Adults With Osteogenesis Imperfecta

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT03638128

Collaborator

(none)

Enrollment

Locations

Arms

44.1

Actual Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate long-term safety of denosumab in subjects with pediatric osteogenesis imperfecta (OI) who completed end of study (EOS) on Study 20130173.

Condition or Disease	Intervention/Treatment	Phase
Osteogenesis Imperfecta (OI)	Drug: Denosumab Other: No treatment Drug: Alternative osteoporosis medications	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Multicenter, Single-arm Open-label Extension Study to Assess Long-term Safety and Efficacy of Current or Prior Treatment With Denosumab in Children/Young Adults With Osteogenesis Imperfecta

Actual Study Start Date :

Jul 26, 2018

Actual Primary Completion Date :

Mar 28, 2022

Actual Study Completion Date :

Mar 28, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Denosumab 3-Month Dosing Regimen	Drug: Denosumab clear, colorless to slightly yellow, preservative free liquid, in single-use 3.0 mL glass vials containing a deliverable dose of 120mg/1.7 mL (70 mg/mL).
Active Comparator: Alternative Treatment Alternative osteoporosis medication/s at the discretion of the investigator, including the commercially available denosumab on a 6-month dosing regimen.	Drug: Denosumab clear, colorless to slightly yellow, preservative free liquid, in single-use 3.0 mL glass vials containing a deliverable dose of 120mg/1.7 mL (70 mg/mL). Drug: Alternative osteoporosis medications Alternative osteoporosis medication/s at the discretion of the investigator.
Active Comparator: No Intervention Subjects who discontinue any osteoporosis medication when joining Study 20170534 for off-treatment observation.	Other: No treatment No treatment administered for off-treatment observation.

Arm

Intervention/Treatment

Experimental: Denosumab 3-Month Dosing Regimen

Drug: Denosumab

clear, colorless to slightly yellow, preservative free liquid, in single-use 3.0 mL glass vials containing a deliverable dose of 120mg/1.7 mL (70 mg/mL).

Active Comparator: Alternative Treatment

Alternative osteoporosis medication/s at the discretion of the investigator, including the commercially available denosumab on a 6-month dosing regimen.

Drug: Denosumab

clear, colorless to slightly yellow, preservative free liquid, in single-use 3.0 mL glass vials containing a deliverable dose of 120mg/1.7 mL (70 mg/mL).

Drug: Alternative osteoporosis medications

Alternative osteoporosis medication/s at the discretion of the investigator.

Active Comparator: No Intervention

Subjects who discontinue any osteoporosis medication when joining Study 20170534 for off-treatment observation.

Other: No treatment

No treatment administered for off-treatment observation.

Outcome Measures

Primary Outcome Measures

Subject incidence of treatment-emergent adverse events. [30 Months]
Subject incidence of serious treatment-emergent adverse events. [30 Months]
Subject incidence of treatment-emergent adverse events of special interest. [30 Months]
Subject incidence of antidenosumab antibodies. [30 Months]
Number of subjects with clinically significant changes from baseline in laboratory values. [Baseline to 30 Months]
Number of subjects with clinically significant changes from baseline in vital signs. [Baseline to 30 Months]
Subject incidence of metaphyseal index Z-score above age-appropriate normal range. [30 Months]
Subject incidence of abnormal molar eruption. [30 Months]
Subject incidence of mandibular shaping. [30 Months]

Secondary Outcome Measures

Denosumab 3-Month regimen in 20170534: Change from baseline in bone mineral density (BMD) of lumbar spine and proximal femur [Baseline to 6, 12, and 24 months]
Changes in BMD Z score of lumbar spine and proximal femur (total hip and femoral neck) from Study 20170534 baseline, as assessed by dual X-ray absorptiometry (DXA), to 6, 12, and 24 months.
Denosumab 3-Month regimen in 20170534: Actual values of bone mineral density (BMD) of lumbar spine and proximal femur [Baseline and at 6, 12, and 24 months]
Actual values of BMD Z score of lumbar spine and proximal femur (total hip and femoral neck) at Study 20170534 baseline, as assessed by DXA, and at 6, 12, and 24 months.

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subject has provided informed consent/assent prior to initiation of any Study 20170534 specific activities/procedures. Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated.
Subject is currently/was enrolled in Study 20130173 and completed the 20130173 End of Study (EOS) visit (regardless of completing or ending investigational product early) OR subjects who do not reconsent/rassent to transition to 3-Month Dosing Regimen on Study 20130173 are also eligible for enrollment OR early terminated from Study 20130173 as a result of meeting BMD Z-score investigational product stopping criteria and was required to early terminate from the study.

Exclusion Criteria:

Treatment with any prohibited proscribed medications while receiving denosumab. Eligibility into study treatment with alternative osteoporosis medication/s of investigator's choice, follow guidelines per the specific alternative osteoporosis medication/s selected. For subjects off-treatment (observation only), no prohibited medications apply.- Subjects currently receiving treatment in another investigational device or drug study other than Study 20130173. Other investigational procedures while participating in this study are excluded.
For subjects expected to receive investigational product (denosumab) at study day 1: Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 5 months after the last dose of denosumab. Females of childbearing potential (Tanner Stage greater than or equal to 2) should only be included in the study after a negative highly sensitive urine or serum pregnancy test. For study treatment with alternative osteoporosis medication/s of investigator's choice, follow guidelines per the specific alternative osteoporosis medication/s selected. For Subjects off-treatment (observation only), no exclusion applies.
For subjects expected to receive investigational product (denosumab) at study day 1: Female subjects of childbearing potential unwilling to practice true sexual abstinence (refrain from heterosexual intercourse) or use 1 highly effective method of contraception during treatment and for an additional 5 months after the last dose of investigational product (denosumab). For study treatment with alternative osteoporosis medication/s of investigator's choice, follow contraception guidelines per the specific alternative osteoporosis medication/s selected. For subjects not receiving any investigational product (observation only), no contraception required.
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital of Los Angeles	Los Angeles	California	United States	90027
2	Indiana University - Riley Hospital for Children	Indianapolis	Indiana	United States	46202
3	The Childrens Hospital at Westmead	Westmead	New South Wales	Australia	2145
4	Perth Childrens Hospital	Nedlands	Western Australia	Australia	6909
5	Universite Catholique de Louvain Cliniques Universitaires Saint Luc	Bruxelles		Belgium	1200
6	Childrens Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
7	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
8	Shriners Hospital for Children	Montreal	Quebec	Canada	H4A 0A9
9	Fakultni nemocnice Plzen	Plzen		Czechia	305 99
10	Thomayerova nemocnice	Praha 4		Czechia	140 59
11	Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin	Bordeaux Cedex		France	33076
12	Hopital Necker Enfants Malades	Paris Cedex 15		France	75743
13	Uniklinik Köln	Köln		Germany	50931
14	Semmelweis Egyetem	Budapest		Hungary	1094
15	Azienda Ospedaliera Policlinico Umberto I	Roma		Italy	00161
16	SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi	Lodz		Poland	91-738
17	Hospital Sant Joan de Deu	Esplugues de Llobregat	Cataluña	Spain	08950
18	Hospital Universitari i Politecnic La Fe	Valencia	Comunidad Valenciana	Spain	46026
19	Birmingham Childrens Hospital	Birmingham		United Kingdom	B4 6NH
20	Bristol Royal Hospital for Children	Bristol		United Kingdom	BS2 8AE
21	Royal Hospital for Children	Glasgow		United Kingdom	G51 4TF
22	Sheffield Childrens Hospital	Sheffield		United Kingdom	S10 2TH

Sponsors and Collaborators

Amgen

Investigators

Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

AmgenTrials clinical trials website

Publications

None provided.

Responsible Party:

Amgen

ClinicalTrials.gov Identifier:

NCT03638128

Other Study ID Numbers:

20170534
2018-000550-21

First Posted:

Aug 20, 2018

Last Update Posted:

Apr 18, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Amgen

Bone.

Additional relevant MeSH terms:

Osteogenesis Imperfecta

Denosumab

Study Results

No Results Posted as of Apr 18, 2022