Study of Lumasiran in Healthy Adults and Patients With Primary Hyperoxaluria Type 1
Sponsor
Alnylam Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02706886
Collaborator
(none)
52
9
9
34.5
5.8
0.2
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of lumasiran in healthy adult volunteers and subjects with primary hyperoxaluria type 1 (PH1). In Part A, single ascending dose (SAD) part, healthy adults were dosed with lumasiran or placebo once. In Part B, multiple ascending doses (MAD) part, patients with primary hyperoxaluria type 1 (PH1) were dosed with lumasiran or placebo. All patients that initially received placebo received lumasiran after completing placebo dosing.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
52 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, Single-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Study of Subcutaneously Administered ALN-GO1 in Healthy Adult Subjects, and Patients With Primary Hyperoxaluria Type 1
Actual Study Start Date
:
Mar 8, 2016
Actual Primary Completion Date
:
Jan 23, 2019
Actual Study Completion Date
:
Jan 23, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Part A: SAD: Placebo A single dose of matching placebo will be administered subcutaneously (SC). |
Drug: Placebo
Matching placebo (sterile saline: 0.9% sodium chloride [NaCl]) will be administered SC once in Part A. In Part B matching placebo will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).
|
| Experimental: Part A: SAD: Lumasiran 0.3 mg/kg A single dose of 0.3 mg/kg lumasiran will be administered SC. |
Drug: Lumasiran
Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).
Other Names:
|
| Experimental: Part A: SAD: Lumasiran 1.0 mg/kg A single dose of 1.0 mg/kg lumasiran will be administered SC. |
Drug: Lumasiran
Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).
Other Names:
|
| Experimental: Part A: SAD: Lumasiran 3.0 mg/kg A single dose of 3.0 mg/kg lumasiran will be administered SC. |
Drug: Lumasiran
Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).
Other Names:
|
| Experimental: Part A: SAD: Lumasiran 6.0 mg/kg A single dose of 6.0 mg/kg lumasiran will be administered SC. |
Drug: Lumasiran
Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).
Other Names:
|
| Placebo Comparator: Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) will be treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo treated participants will cross over to their respective Part B lumasiran arms in the Part B: MAD Study Day 85-End of Study Period and will then be treated with lumasiran. The estimated total time on study was up to 546 days. |
Drug: Placebo
Matching placebo (sterile saline: 0.9% sodium chloride [NaCl]) will be administered SC once in Part A. In Part B matching placebo will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).
|
| Experimental: Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 will be treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85. |
Drug: Lumasiran
Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).
Other Names:
|
| Experimental: Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85. |
Drug: Lumasiran
Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).
Other Names:
|
| Experimental: Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85. |
Drug: Lumasiran
Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events (AEs) [Part A (SAD): Up to 405 days; Part B (MAD): Up to 546 days]
An AE is any untoward medical occurrence in a clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Secondary Outcome Measures
- Maximum Concentration (Cmax) of Lumasiran in Plasma [Part A (SAD): Day 1: predose, 30 minutes (min), 1 hour (h), 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h]
Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.
- Time to Cmax (Tmax) of Lumasiran in Plasma [Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h]
Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.
- Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma [Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h]
Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.
- Terminal Half-life (t1/2) of Lumasiran in Plasma [Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h]
Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.
- Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran [Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h]
Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.
- Renal Clearance (CLR) of Lumasiran [Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h]
Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.
- Baseline Plasma Glycolate Concentration [Part A (SAD): Baseline, Part B (MAD): Baseline]
The pharmacodynamic (PD) outcome measure of plasma glycolate concentration could only be calculated for Part A. Due to an issue with the plasma glycolate assay at the testing laboratory the data for Part B could not be calculated.
- Percentage Change From Baseline in Plasma Glycolate Concentration [Part A (SAD): Days 15, 29, 57 and 85; Part B (MAD): Days 15, 29, 57, 85]
The PD outcome measure of plasma glycolate concentration could only be calculated for Part A. Due to an issue with the plasma glycolate assay at the testing laboratory the data for Part B could not be calculated.
- Baseline Spot Urine Glycolate:Creatinine Ratio in Part A [Part A (SAD): Baseline]
The endpoint was only measured in Part A.
- Percentage Change From Baseline in Spot Urine Glycolate:Creatinine Ratio in Part A [Part A (SAD): Days 29 and 57]
The endpoint was only measured in Part A.
- Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B [Part B (MAD): Baseline]
The endpoint was only measured in Part B.
- Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B [Part B (MAD): 24 hour urine collections on Days 29, 57, 85, 113, 141, 169, 197]
The endpoint was only measured in Part B.
- Baseline 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days [Part B (MAD): Baseline]
The endpoint was only measured during the initial 85 days in Part B.
- Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days [Part B (MAD): 24 hour urine collections on Days 29, 57 and 85]
The endpoint was only measured during the initial 85 days in Part B.
- Baseline Creatinine Clearance Corrected for BSA in Part B [Part B (MAD): Baseline]
- Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B [Part B (MAD): Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449]
Eligibility Criteria
Criteria
Ages Eligible for Study:
6 Years
to 64 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria for Parts A and B:
-
Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception.
-
Willing to provide written informed consent and to comply with study requirements.
Additional Inclusion Criteria for Part B:
-
Confirmation of PH1 disease
-
Meet 24 hour urine oxalate excretion requirements
-
Estimated glomerular filtration rate (GFR) of >45 mL/min/1.73m^2
-
If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days
Exclusion Criteria for Parts A and B:
- Clinically significant health concerns (with the exception of PH1 for patients in Part
-
Clinically significant electrocardiogram (ECG) abnormalities
-
Abnormal for aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and any other clinical safety laboratory result considered clinically significant
-
Received an investigational agent within 3 months before the first dose of study drug or are in follow-up of another clinical study
-
Known history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc)
-
History of intolerance to subcutaneous injection
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Trial Site | Bordeaux | France | ||
| 2 | Clinical Trial Site | Lyon | France | ||
| 3 | Clinical Trial Site | Paris | France | ||
| 4 | Clinical Trial Site | Bonn | Germany | ||
| 5 | Clinical Trial Site | Haifa | Israel | ||
| 6 | Clinical Trial Site | Jerusalem | Israel | ||
| 7 | Clinical Trial Site | Amsterdam | Netherlands | ||
| 8 | Clinical Trial Site | Birmingham | United Kingdom | ||
| 9 | Clinical Trial Site | London | United Kingdom |
Sponsors and Collaborators
- Alnylam Pharmaceuticals
Investigators
- Study Director: Tracy McGregor, MD, MSCI, Alnylam Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02706886
Other Study ID Numbers:
- ALN-GO1-001
- 2015-004407-23
First Posted:
Mar 11, 2016
Last Update Posted:
Jan 30, 2020
Last Verified:
Jan 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Alnylam Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at ten sites in Germany, France, the United Kingdom, Israel, and the Netherlands. |
|---|---|
| Pre-assignment Detail | In Part A, single ascending dose (SAD) part, healthy adults were dosed with lumasiran or placebo once. In Part B, multiple ascending doses (MAD) part, patients with primary hyperoxaluria type 1 (PH1) were dosed with lumasiran or placebo. All patients, who initially received placebo, received lumasiran after completing placebo dosing. |
| Arm/Group Title | Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of matching placebo was administered subcutaneously (SC). | A single dose of 0.3 mg/kg lumasiran was administered SC. | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Period Title: Part A: SAD Period | |||||||||
| STARTED | 8 | 6 | 6 | 6 | 6 | 0 | 0 | 0 | 0 |
| COMPLETED | 8 | 6 | 6 | 4 | 6 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Part A: SAD Period | |||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 3 | 7 | 7 | 3 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 3 | 7 | 7 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Part A: SAD Period | |||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 8 | 4 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 8 | 4 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of matching placebo was administered SC. | A single dose of 0.3 mg/kg lumasiran was administered SC. | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Total of all reporting groups |
| Overall Participants | 8 | 6 | 6 | 6 | 6 | 3 | 7 | 7 | 3 | 52 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||||
| Mean (Standard Deviation) [years] |
29.8
(6.25)
|
28.8
(7.36)
|
30.2
(7.81)
|
27.3
(3.44)
|
28.8
(5.46)
|
20.7
(19.40)
|
14.0
(9.93)
|
15.4
(7.89)
|
9.7
(5.51)
|
23.6
(10.41)
|
| Sex: Female, Male (Count of Participants) | ||||||||||
| Female |
5
62.5%
|
0
0%
|
3
50%
|
3
50%
|
5
83.3%
|
1
33.3%
|
6
85.7%
|
4
57.1%
|
2
66.7%
|
29
55.8%
|
| Male |
3
37.5%
|
6
100%
|
3
50%
|
3
50%
|
1
16.7%
|
2
66.7%
|
1
14.3%
|
3
42.9%
|
1
33.3%
|
23
44.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||||
| Hispanic or Latino |
1
12.5%
|
1
16.7%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
5.8%
|
| Not Hispanic or Latino |
7
87.5%
|
5
83.3%
|
6
100%
|
6
100%
|
5
83.3%
|
3
100%
|
7
100%
|
7
100%
|
3
100%
|
49
94.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
12.5%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
33.3%
|
2
28.6%
|
1
14.3%
|
0
0%
|
6
11.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
3.8%
|
| White |
7
87.5%
|
6
100%
|
5
83.3%
|
3
50%
|
4
66.7%
|
2
66.7%
|
5
71.4%
|
5
71.4%
|
3
100%
|
40
76.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
16.7%
|
1
16.7%
|
1
16.7%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
4
7.7%
|
Outcome Measures
| Title | Number of Participants With Adverse Events (AEs) |
|---|---|
| Description | An AE is any untoward medical occurrence in a clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. |
| Time Frame | Part A (SAD): Up to 405 days; Part B (MAD): Up to 546 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set consisted of all healthy participants and patients, who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms. |
| Arm/Group Title | Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of matching placebo was administered SC. | A single dose of 0.3 mg/kg Lumasiran was administered SC. | A single dose of 1.0 mg/kg Lumasiran was administered SC. | A single dose of 3.0 mg/kg Lumasiran was administered SC. | A single dose of 6.0 mg/kg Lumasiran was administered SC. | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 8 | 6 | 6 | 6 | 6 | 3 | 8 | 8 | 4 |
| Count of Participants [Participants] |
5
62.5%
|
6
100%
|
2
33.3%
|
6
100%
|
6
100%
|
2
66.7%
|
8
114.3%
|
7
100%
|
4
133.3%
|
| Title | Maximum Concentration (Cmax) of Lumasiran in Plasma |
|---|---|
| Description | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. |
| Time Frame | Part A (SAD): Day 1: predose, 30 minutes (min), 1 hour (h), 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. |
| Arm/Group Title | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of 0.3 mg/kg lumasiran was administered SC. | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 6 | 6 | 6 | 6 | 8 | 8 | 4 |
| Day 1 |
39.7940
(8.58882)
|
204.3748
(111.68091)
|
533.4527
(160.11060)
|
1176.1302
(199.89797)
|
324.1386
(489.71104)
|
582.4515
(266.90105)
|
432.2798
(245.02660)
|
| Day 57 |
147.6780
(67.97968)
|
701.1708
(511.63001)
|
|||||
| Day 85 |
411.5613
(174.92146)
|
| Title | Time to Cmax (Tmax) of Lumasiran in Plasma |
|---|---|
| Description | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. |
| Time Frame | Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. |
| Arm/Group Title | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of 0.3 mg/kg lumasiran was administered SC. | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 6 | 6 | 6 | 6 | 8 | 8 | 4 |
| Day 1 |
5.0167
|
1.5000
|
3.0000
|
7.0000
|
3.9917
|
4.9917
|
9.0000
|
| Day 57 |
3.0417
|
2.9833
|
|||||
| Day 85 |
5.9833
|
| Title | Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma |
|---|---|
| Description | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. |
| Time Frame | Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. |
| Arm/Group Title | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of 0.3 mg/kg lumasiran was administered subcutaneously (SC). | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 6 | 6 | 6 | 6 | 8 | 8 | 4 |
| Day 1 |
293.5232
(96.86989)
|
1899.8119
(558.25326)
|
7211.5890
(1125.64173)
|
16778.0579
(4380.15325)
|
1428.0412
(697.85233)
|
7400.2181
(2331.89843)
|
6337.9082
(3840.03340)
|
| Day 57 |
1608.1457
(708.95156)
|
7959.7873
(1726.57675)
|
|||||
| Day 85 |
5136.3462
(2757.90139)
|
| Title | Terminal Half-life (t1/2) of Lumasiran in Plasma |
|---|---|
| Description | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. |
| Time Frame | Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. |
| Arm/Group Title | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 2 | 2 | 1 | 4 | 5 | 1 |
| Day 1 |
7.0655
(0.37379)
|
5.9798
(1.52471)
|
3.4683
(NA)
|
3.2670
(1.52759)
|
5.4574
(3.49432)
|
7.8028
(NA)
|
| Day 57 |
7.8090
(4.52009)
|
5.8356
(3.12156)
|
||||
| Day 85 |
4.6694
(NA)
|
| Title | Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran |
|---|---|
| Description | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. |
| Time Frame | Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. |
| Arm/Group Title | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of 0.3 mg/kg lumasiran was administered SC. | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 6 | 6 | 6 | 5 | 8 | 7 | 4 |
| Day 1 |
17.4219
(2.44129)
|
19.0713
(3.88914)
|
21.0472
(5.36667)
|
25.7931
(3.25937)
|
11.0895
(3.74207)
|
11.1877
(6.07719)
|
7.1691
(2.37465)
|
| Day 57 |
9.4698
(4.21949)
|
12.4604
(4.02897)
|
|||||
| Day 85 |
13.6938
(3.60004)
|
| Title | Renal Clearance (CLR) of Lumasiran |
|---|---|
| Description | Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups. |
| Time Frame | Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data. |
| Arm/Group Title | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of 0.3 mg/kg lumasiran was administered SC. | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 1 | 5 | 6 | 5 | 7 | 6 | 4 |
| Day 1 |
8.7817
(NA)
|
5.4906
(2.07402)
|
5.8211
(1.31377)
|
6.3417
(1.15497)
|
2.2612
(1.17616)
|
2.3818
(1.13067)
|
2.0564
(1.20600)
|
| Day 57 |
1.9610
(1.11228)
|
2.5150
(0.80386)
|
|||||
| Day 85 |
3.3663
(1.18371)
|
| Title | Baseline Plasma Glycolate Concentration |
|---|---|
| Description | The pharmacodynamic (PD) outcome measure of plasma glycolate concentration could only be calculated for Part A. Due to an issue with the plasma glycolate assay at the testing laboratory the data for Part B could not be calculated. |
| Time Frame | Part A (SAD): Baseline, Part B (MAD): Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis Set consisted of all participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood sample available that was evaluable for PD assessments. Due to an issue with plasma glycolate assay at the testing laboratory the data for Part B could not be calculated. |
| Arm/Group Title | Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of matching placebo was administered SC. | A single dose of 0.3 mg/kg lumasiran was administered SC. | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebotreated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 8 | 6 | 6 | 6 | 6 | 0 | 0 | 0 | 0 |
| Mean (Standard Deviation) [umol/L] |
5.1
(1.73)
|
5.3
(1.51)
|
5.7
(1.97)
|
6.2
(2.56)
|
4.8
(1.72)
|
| Title | Percentage Change From Baseline in Plasma Glycolate Concentration |
|---|---|
| Description | The PD outcome measure of plasma glycolate concentration could only be calculated for Part A. Due to an issue with the plasma glycolate assay at the testing laboratory the data for Part B could not be calculated. |
| Time Frame | Part A (SAD): Days 15, 29, 57 and 85; Part B (MAD): Days 15, 29, 57, 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis Set consisted of all participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood sample available that was evaluable for PD assessments. Due to an issue with plasma glycolate assay at the testing laboratory the data for Part B could not be calculated. |
| Arm/Group Title | Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | A single dose of matching placebo was administered SC. | A single dose of 0.3 mg/kg lumasiran was administered SC. | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebotreated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 8 | 6 | 6 | 6 | 6 | 0 | 0 | 0 | 0 |
| Day 15 |
18.3
(67.19)
|
58.3
(55.29)
|
48.5
(82.99)
|
56.4
(28.50)
|
59.5
(49.00)
|
||||
| Day 29 |
22.4
(46.83)
|
32.9
(57.67)
|
70.6
(82.74)
|
146.4
(81.99)
|
390.1
(270.40)
|
||||
| Day 57 |
126.7
(242.68)
|
66.3
(38.07)
|
109.8
(124.29)
|
230.1
(180.36)
|
730.4
(439.54)
|
||||
| Day 85 |
31.2
(131.04)
|
15.6
(100.54)
|
40.7
(110.75)
|
196.2
(152.41)
|
731.3
(375.02)
|
| Title | Baseline Spot Urine Glycolate:Creatinine Ratio in Part A |
|---|---|
| Description | The endpoint was only measured in Part A. |
| Time Frame | Part A (SAD): Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis Set for Part A consisted of all healthy participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. |
| Arm/Group Title | Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | A single dose of matching placebo was administered SC. | A single dose of 0.3 mg/kg lumasiran was administered SC. | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. |
| Measure Participants | 8 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [mg/g] |
12.4
(4.63)
|
15.7
(4.27)
|
15.7
(3.14)
|
13.0
(3.52)
|
14.8
(4.31)
|
| Title | Percentage Change From Baseline in Spot Urine Glycolate:Creatinine Ratio in Part A |
|---|---|
| Description | The endpoint was only measured in Part A. |
| Time Frame | Part A (SAD): Days 29 and 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis Set in Part A consisted of all healthy participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. |
| Arm/Group Title | Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | A single dose of matching placebo was administered SC. | A single dose of 0.3 mg/kg lumasiran was administered SC. | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. |
| Measure Participants | 8 | 6 | 6 | 6 | 6 |
| Day 29 |
8.1
(43.42)
|
32.5
(22.6)
|
82.9
(65.00)
|
109.1
(66.51)
|
210.5
(199.30)
|
| Day 57 |
73.8
(108.9)
|
38.0
(50.62)
|
47.8
(41.03)
|
215.0
(178.72)
|
310.7
(94.51)
|
| Title | Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B |
|---|---|
| Description | The endpoint was only measured in Part B. |
| Time Frame | Part B (MAD): Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. |
| Arm/Group Title | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|
| Arm/Group Description | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 3 | 8 | 8 | 4 |
| Mean (Standard Deviation) [mmol/24h/1.73m^2] |
1.96
(0.321)
|
1.73
(0.696)
|
1.84
(0.621)
|
1.30
(0.350)
|
| Title | Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B |
|---|---|
| Description | The endpoint was only measured in Part B. |
| Time Frame | Part B (MAD): 24 hour urine collections on Days 29, 57, 85, 113, 141, 169, 197 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. |
| Arm/Group Title | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|
| Arm/Group Description | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 2 | 8 | 8 | 4 |
| Day 29 |
-2.4
(NA)
|
-41.1
(24.76)
|
-57.5
(10.84)
|
-49.2
(5.40)
|
| Day 57 |
-27.8
(47.11)
|
-49.7
(20.08)
|
-72.5
(10.70)
|
-49.1
(5.82)
|
| Day 85 |
9.1
(NA)
|
-65.6
(16.64)
|
-68.4
(10.60)
|
-53.3
(3.66)
|
| Day 113 |
-61.4
(12.24)
|
-78.1
(7.80)
|
-59.1
(20.75)
|
|
| Day 141 |
-64.6
(13.55)
|
-73.5
(8.11)
|
-68.4
(3.21)
|
|
| Day 169 |
-61.6
(14.19)
|
-69.3
(9.61)
|
-48.7
(14.19)
|
|
| Day 197 |
-63.8
(13.85)
|
-71.2
(11.70)
|
-52.7
(6.38)
|
| Title | Baseline 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days |
|---|---|
| Description | The endpoint was only measured during the initial 85 days in Part B. |
| Time Frame | Part B (MAD): Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. |
| Arm/Group Title | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|
| Arm/Group Description | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 3 | 7 | 7 | 3 |
| Mean (Standard Deviation) [mg/g] |
193
(117.2)
|
241
(85.6)
|
289
(146.0)
|
281
(139.0)
|
| Title | Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days |
|---|---|
| Description | The endpoint was only measured during the initial 85 days in Part B. |
| Time Frame | Part B (MAD): 24 hour urine collections on Days 29, 57 and 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. |
| Arm/Group Title | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|
| Arm/Group Description | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 3 | 7 | 7 | 3 |
| Day 29 |
-15.1
(6.47)
|
53.1
(42.18)
|
31.4
(35.99)
|
33.0
(36.37)
|
| Day 57 |
-13.8
(29.02)
|
82.3
(40.12)
|
42.3
(57.56)
|
81.8
(35.66)
|
| Day 85 |
-23.0
(10.45)
|
71.0
(55.62)
|
43.7
(62.15)
|
42.0
(20.86)
|
| Title | Baseline Creatinine Clearance Corrected for BSA in Part B |
|---|---|
| Description | |
| Time Frame | Part B (MAD): Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. |
| Arm/Group Title | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|
| Arm/Group Description | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 3 | 8 | 8 | 4 |
| Mean (Standard Deviation) [mL/min/1.73 m^2] |
64.389
(19.8024)
|
108.149
(44.1783)
|
86.268
(22.1226)
|
88.251
(30.0118)
|
| Title | Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B |
|---|---|
| Description | |
| Time Frame | Part B (MAD): Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments. |
| Arm/Group Title | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M |
|---|---|---|---|---|
| Arm/Group Description | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85. |
| Measure Participants | 2 | 8 | 8 | 4 |
| Day 29 |
9.019
(NA)
|
-6.672
(11.9614)
|
-0.624
(15.1771)
|
2.748
(5.6858)
|
| Day 57 |
20.184
(23.5572)
|
-8.426
(19.7271)
|
4.505
(35.2457)
|
37.030
(56.1210)
|
| Day 85 |
-5.945
(NA)
|
-13.536
(22.8679)
|
-3.720
(22.6231)
|
-6.113
(43.5441)
|
| Day 113 |
-14.424
(24.1107)
|
3.444
(29.6749)
|
7.570
(40.5928)
|
|
| Day 141 |
-8.804
(27.4802)
|
9.315
(27.5044)
|
-30.691
(12.8912)
|
|
| Day 169 |
-19.796
(31.7492)
|
-8.544
(14.8481)
|
20.210
(NA)
|
|
| Day 197 |
-8.546
(13.5672)
|
-13.513
(25.0560)
|
28.857
(22.1891)
|
|
| Day 225 |
-18.221
(14.2322)
|
29.013
(53.5563)
|
-14.964
(9.9130)
|
|
| Day 253 |
-5.140
(19.2839)
|
10.232
(24.4929)
|
||
| Day 281 |
-14.283
(22.6126)
|
5.841
(13.0381)
|
||
| Day 309 |
-0.403
(34.6839)
|
8.441
(11.5329)
|
||
| Day 337 |
-5.168
(31.0756)
|
8.688
(24.2094)
|
||
| Day 365 |
2.268
(33.7565)
|
9.201
(14.4856)
|
||
| Day 393 |
-11.942
(45.3027)
|
-4.484
(12.6320)
|
||
| Day 421 |
7.610
(11.2195)
|
-6.498
(12.9022)
|
||
| Day 449 |
-15.093
(10.3705)
|
Adverse Events
| Time Frame | Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event. | |||||||||||||||||
| Arm/Group Title | Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M | |||||||||
| Arm/Group Description | A single dose of matching placebo was administered. | A single dose of 0.3 mg/kg lumasiran was administered subcutaneously (SC). | A single dose of 1.0 mg/kg lumasiran was administered SC. | A single dose of 3.0 mg/kg lumasiran was administered SC. | A single dose of 6.0 mg/kg lumasiran was administered SC. | Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in the All-Lumasiran-Treated Period. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. | Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. | |||||||||
All Cause Mortality |
||||||||||||||||||
| Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
Serious Adverse Events |
||||||||||||||||||
| Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 1/8 (12.5%) | 3/8 (37.5%) | 0/4 (0%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Vomiting | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 2/8 (25%) | 0/4 (0%) | |||||||||
| Abdominal pain | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| General disorders | ||||||||||||||||||
| Pyrexia | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Infections and infestations | ||||||||||||||||||
| Pyelonephritis acute | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Gastroenteritis | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Renal and urinary disorders | ||||||||||||||||||
| Nephrolithiasis | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||
| Part A: SAD: Placebo | Part A: SAD: Lumasiran 0.3 mg/kg | Part A: SAD: Lumasiran 1.0 mg/kg | Part A: SAD: Lumasiran 3.0 mg/kg | Part A: SAD: Lumasiran 6.0 mg/kg | Part B: MAD: Placebo | Part B: MAD: Lumasiran 1.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg qM | Part B: MAD: Lumasiran 3.0 mg/kg q3M | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/8 (62.5%) | 6/6 (100%) | 3/6 (50%) | 6/6 (100%) | 6/6 (100%) | 2/3 (66.7%) | 7/8 (87.5%) | 7/8 (87.5%) | 4/4 (100%) | |||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||
| Lymph node pain | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Cardiac disorders | ||||||||||||||||||
| Tricuspid valve incompetence | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Congenital, familial and genetic disorders | ||||||||||||||||||
| Atrial septal defect | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Eye disorders | ||||||||||||||||||
| Visual impairment | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Dry eye | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Eye swelling | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Abdominal discomfort | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Abdominal pain | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 1/8 (12.5%) | 3/8 (37.5%) | 1/4 (25%) | |||||||||
| Diarrhoea | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Faeces soft | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Flatulence | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Nausea | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Constipation | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Toothache | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Vomiting | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/8 (0%) | 1/8 (12.5%) | 1/4 (25%) | |||||||||
| Abdominal pain upper | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Teething | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | |||||||||
| General disorders | ||||||||||||||||||
| Fatigue | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 2/8 (25%) | 0/4 (0%) | |||||||||
| Injection site pain | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 4/6 (66.7%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Injection site bruising | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Injection site erythema | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Injection site pruritus | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Pyrexia | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 1/8 (12.5%) | 1/8 (12.5%) | 1/4 (25%) | |||||||||
| Axillary pain | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Influenza like illness | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Injection site discolouration | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Injection site swelling | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Infections and infestations | ||||||||||||||||||
| Gastroenteritis | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Influenza | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Nasopharyngitis | 3/8 (37.5%) | 1/6 (16.7%) | 1/6 (16.7%) | 4/6 (66.7%) | 4/6 (66.7%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 2/4 (50%) | |||||||||
| Periodontitis | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Sinusitis | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Tonsillitis | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Upper respiratory tract infection | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Urinary tract infection | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Viral pharyngitis | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Pharyngitis | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Rhinitis | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/8 (12.5%) | 3/8 (37.5%) | 0/4 (0%) | |||||||||
| Urinary tract infection enterococcal | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Body tinea | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Dermatitis infected | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Urinary tract infection bacterial | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Urinary tract infection staphylococcal | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||
| Contusion | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/3 (33.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Head injury | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Laceration | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Tendon injury | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Arthropod bite | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Soft tissue injury | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Investigations | ||||||||||||||||||
| Alanine aminotransferase increased | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Aspartate aminotransferase increased | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Blood creatine phosphokinase increased | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Blood phosphorus decreased | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | |||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||
| Gout | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | |||||||||
| Increased appetite | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Overweight | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | |||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||
| Back pain | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Musculoskeletal chest pain | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Myalgia | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Arthralgia | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Groin pain | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Nervous system disorders | ||||||||||||||||||
| Headache | 1/8 (12.5%) | 1/6 (16.7%) | 2/6 (33.3%) | 1/6 (16.7%) | 3/6 (50%) | 0/3 (0%) | 2/8 (25%) | 2/8 (25%) | 0/4 (0%) | |||||||||
| Migraine | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Presyncope | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Lethargy | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Psychiatric disorders | ||||||||||||||||||
| Alcoholic hangover | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Renal and urinary disorders | ||||||||||||||||||
| Dysuria | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/8 (12.5%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Nephrolithiasis | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 3/8 (37.5%) | 0/4 (0%) | |||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||
| Nasal discomfort | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Oropharyngeal pain | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Cough | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/8 (12.5%) | 2/8 (25%) | 0/4 (0%) | |||||||||
| Rhinitis allergic | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | |||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||
| Papule | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Rash follicular | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Skin texture abnormal | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Blister | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | |||||||||
| Rash | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | |||||||||
| Social circumstances | ||||||||||||||||||
| Caffeine consumption | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Alnylam Pharmaceuticals Inc |
| Phone | 866-330-0326 |
| Clinicaltrials@alnylam.com |
Responsible Party:
Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02706886
Other Study ID Numbers:
- ALN-GO1-001
- 2015-004407-23
First Posted:
Mar 11, 2016
Last Update Posted:
Jan 30, 2020
Last Verified:
Jan 1, 2020