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Study of Lumasiran in Healthy Adults and Patients With Primary Hyperoxaluria Type 1

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ClinicalTrials.gov Identifier: NCT02706886
Recruitment Status : Completed
First Posted : March 11, 2016
Results First Posted : January 30, 2020
Last Update Posted : January 30, 2020
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Condition Primary Hyperoxaluria Type 1 (PH1)
Interventions Drug: Lumasiran
Drug: Placebo
Enrollment 52
Recruitment Details Participants were enrolled at ten sites in Germany, France, the United Kingdom, Israel, and the Netherlands.
Pre-assignment Details 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
Hide 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
Reason Not Completed
Withdrawal by Subject             0             0             0             2             0             0             0             0             0
Period Title: Part B: MAD Study Days 1-85
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 B: MAD Study Day 85-End of Study
Started 0 0 0 0 0 0 8 [1] 8 [1] 4 [1]
Completed 0 0 0 0 0 0 8 8 4
Not Completed 0 0 0 0 0 0 0 0 0
[1]
One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm.
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
Hide 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 Number of Baseline Participants 8 6 6 6 6 3 7 7 3 52
Hide Baseline Analysis Population Description
Safety Analysis Set consisted of all healthy participants and participants who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received during the first period that they entered the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 3 participants 7 participants 7 participants 3 participants 52 participants
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 3 participants 7 participants 7 participants 3 participants 52 participants
Female
5
  62.5%
0
   0.0%
3
  50.0%
3
  50.0%
5
  83.3%
1
  33.3%
6
  85.7%
4
  57.1%
2
  66.7%
29
  55.8%
Male
3
  37.5%
6
 100.0%
3
  50.0%
3
  50.0%
1
  16.7%
2
  66.7%
1
  14.3%
3
  42.9%
1
  33.3%
23
  44.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 3 participants 7 participants 7 participants 3 participants 52 participants
Hispanic or Latino
1
  12.5%
1
  16.7%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   5.8%
Not Hispanic or Latino
7
  87.5%
5
  83.3%
6
 100.0%
6
 100.0%
5
  83.3%
3
 100.0%
7
 100.0%
7
 100.0%
3
 100.0%
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
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 3 participants 7 participants 7 participants 3 participants 52 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
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  12.5%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
1
  33.3%
2
  28.6%
1
  14.3%
0
   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
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   3.8%
White
7
  87.5%
6
 100.0%
5
  83.3%
3
  50.0%
4
  66.7%
2
  66.7%
5
  71.4%
5
  71.4%
3
 100.0%
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
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
  16.7%
1
  16.7%
1
  16.7%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
4
   7.7%
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 6 6 6 6 3 8 8 4
Measure Type: Count of Participants
Unit of Measure: Participants
5
  62.5%
6
 100.0%
2
  33.3%
6
 100.0%
6
 100.0%
2
  66.7%
8
 100.0%
7
  87.5%
4
 100.0%
2.Secondary Outcome
Title Maximum Concentration (Cmax) of Lumasiran in Plasma
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 6 6 6 8 8 4
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 Number Analyzed 6 participants 6 participants 6 participants 6 participants 8 participants 8 participants 4 participants
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 Number Analyzed 0 participants 0 participants 0 participants 0 participants 8 participants 8 participants 0 participants
147.6780  (67.97968) 701.1708  (511.63001)
Day 85 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 3 participants
411.5613  (174.92146)
3.Secondary Outcome
Title Time to Cmax (Tmax) of Lumasiran in Plasma
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 6 6 6 8 8 4
Median (Full Range)
Unit of Measure: hours
Day 1 Number Analyzed 6 participants 6 participants 6 participants 6 participants 8 participants 8 participants 4 participants
5.0167
(4.000 to 8.017)
1.5000
(0.517 to 8.000)
3.0000
(0.500 to 8.000)
7.0000
(0.500 to 8.067)
3.9917
(0.567 to 5.967)
4.9917
(0.533 to 12.000)
9.0000
(5.783 to 12.017)
Day 57 Number Analyzed 0 participants 0 participants 0 participants 0 participants 8 participants 8 participants 0 participants
3.0417
(0.500 to 6.000)
2.9833
(0.500 to 8.000)
Day 85 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 3 participants
5.9833
(4.050 to 7.950)
4.Secondary Outcome
Title Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 6 6 6 8 8 4
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
Day 1 Number Analyzed 6 participants 6 participants 6 participants 6 participants 8 participants 8 participants 4 participants
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 Number Analyzed 0 participants 0 participants 0 participants 0 participants 8 participants 8 participants 0 participants
1608.1457  (708.95156) 7959.7873  (1726.57675)
Day 85 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 3 participants
5136.3462  (2757.90139)
5.Secondary Outcome
Title Terminal Half-life (t1/2) of Lumasiran in Plasma
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 2 2 1 4 5 1
Mean (Standard Deviation)
Unit of Measure: hours
Day 1 Number Analyzed 2 participants 2 participants 1 participants 4 participants 5 participants 1 participants
7.0655  (0.37379) 5.9798  (1.52471) 3.4683 [1]   (NA) 3.2670  (1.52759) 5.4574  (3.49432) 7.8028 [1]   (NA)
Day 57 Number Analyzed 0 participants 0 participants 0 participants 4 participants 4 participants 0 participants
7.8090  (4.52009) 5.8356  (3.12156)
Day 85 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants
4.6694 [1]   (NA)
[1]
SD was not calculated for arms with data for 1 participant.
6.Secondary Outcome
Title Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 6 6 6 5 8 7 4
Mean (Standard Deviation)
Unit of Measure: percentage fractional excretion
Day 1 Number Analyzed 6 participants 6 participants 6 participants 5 participants 7 participants 7 participants 4 participants
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 Number Analyzed 0 participants 0 participants 0 participants 0 participants 8 participants 6 participants 0 participants
9.4698  (4.21949) 12.4604  (4.02897)
Day 85 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 3 participants
13.6938  (3.60004)
7.Secondary Outcome
Title Renal Clearance (CLR) of Lumasiran
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 1 5 6 5 7 6 4
Mean (Standard Deviation)
Unit of Measure: L/h
Day 1 Number Analyzed 1 participants 5 participants 6 participants 5 participants 6 participants 6 participants 4 participants
8.7817 [1]   (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 Number Analyzed 0 participants 0 participants 0 participants 0 participants 7 participants 6 participants 0 participants
1.9610  (1.11228) 2.5150  (0.80386)
Day 85 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 3 participants
3.3663  (1.18371)
[1]
SD was not calculated for arms with data for 1 participant.
8.Secondary Outcome
Title Baseline Plasma Glycolate Concentration
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 6 6 6 6 0 0 0 0
Mean (Standard Deviation)
Unit of Measure: umol/L
5.1  (1.73) 5.3  (1.51) 5.7  (1.97) 6.2  (2.56) 4.8  (1.72)
9.Secondary Outcome
Title Percentage Change From Baseline in Plasma Glycolate Concentration
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 6 6 6 6 0 0 0 0
Mean (Standard Deviation)
Unit of Measure: percentage change from baseline
Day 15 Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 0 participants 0 participants 0 participants 0 participants
18.3  (67.19) 58.3  (55.29) 48.5  (82.99) 56.4  (28.50) 59.5  (49.00)
Day 29 Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 0 participants 0 participants 0 participants 0 participants
22.4  (46.83) 32.9  (57.67) 70.6  (82.74) 146.4  (81.99) 390.1  (270.40)
Day 57 Number Analyzed 8 participants 6 participants 6 participants 6 participants 6 participants 0 participants 0 participants 0 participants 0 participants
126.7  (242.68) 66.3  (38.07) 109.8  (124.29) 230.1  (180.36) 730.4  (439.54)
Day 85 Number Analyzed 8 participants 6 participants 6 participants 5 participants 6 participants 0 participants 0 participants 0 participants 0 participants
31.2  (131.04) 15.6  (100.54) 40.7  (110.75) 196.2  (152.41) 731.3  (375.02)
10.Secondary Outcome
Title Baseline Spot Urine Glycolate:Creatinine Ratio in Part A
Hide Description The endpoint was only measured in Part A.
Time Frame Part A (SAD): Baseline
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: mg/g
12.4  (4.63) 15.7  (4.27) 15.7  (3.14) 13.0  (3.52) 14.8  (4.31)
11.Secondary Outcome
Title Percentage Change From Baseline in Spot Urine Glycolate:Creatinine Ratio in Part A
Hide Description The endpoint was only measured in Part A.
Time Frame Part A (SAD): Days 29 and 57
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: percentage change from baseline
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)
12.Secondary Outcome
Title Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B
Hide Description The endpoint was only measured in Part B.
Time Frame Part B (MAD): Baseline
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 8 8 4
Mean (Standard Deviation)
Unit of Measure: mmol/24h/1.73m^2
1.96  (0.321) 1.73  (0.696) 1.84  (0.621) 1.30  (0.350)
13.Secondary Outcome
Title Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 2 8 8 4
Mean (Standard Deviation)
Unit of Measure: percentage change from baseline
Day 29 Number Analyzed 1 participants 7 participants 7 participants 4 participants
-2.4 [1]   (NA) -41.1  (24.76) -57.5  (10.84) -49.2  (5.40)
Day 57 Number Analyzed 2 participants 7 participants 8 participants 4 participants
-27.8  (47.11) -49.7  (20.08) -72.5  (10.70) -49.1  (5.82)
Day 85 Number Analyzed 1 participants 8 participants 7 participants 3 participants
9.1 [1]   (NA) -65.6  (16.64) -68.4  (10.60) -53.3  (3.66)
Day 113 Number Analyzed 0 participants 7 participants 6 participants 4 participants
-61.4  (12.24) -78.1  (7.80) -59.1  (20.75)
Day 141 Number Analyzed 0 participants 7 participants 7 participants 2 participants
-64.6  (13.55) -73.5  (8.11) -68.4  (3.21)
Day 169 Number Analyzed 0 participants 8 participants 7 participants 3 participants
-61.6  (14.19) -69.3  (9.61) -48.7  (14.19)
Day 197 Number Analyzed 0 participants 6 participants 7 participants 4 participants
-63.8  (13.85) -71.2  (11.70) -52.7  (6.38)
[1]
SD was not calculated for arms with data for 1 participant.
14.Secondary Outcome
Title Baseline 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days
Hide Description The endpoint was only measured during the initial 85 days in Part B.
Time Frame Part B (MAD): Baseline
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 7 7 3
Mean (Standard Deviation)
Unit of Measure: mg/g
193  (117.2) 241  (85.6) 289  (146.0) 281  (139.0)
15.Secondary Outcome
Title Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 7 7 3
Mean (Standard Deviation)
Unit of Measure: percentage change from baseline
Day 29 Number Analyzed 3 participants 7 participants 7 participants 3 participants
-15.1  (6.47) 53.1  (42.18) 31.4  (35.99) 33.0  (36.37)
Day 57 Number Analyzed 3 participants 7 participants 7 participants 3 participants
-13.8  (29.02) 82.3  (40.12) 42.3  (57.56) 81.8  (35.66)
Day 85 Number Analyzed 3 participants 7 participants 7 participants 2 participants
-23.0  (10.45) 71.0  (55.62) 43.7  (62.15) 42.0  (20.86)
16.Secondary Outcome
Title Baseline Creatinine Clearance Corrected for BSA in Part B
Hide Description [Not Specified]
Time Frame Part B (MAD): Baseline
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 8 8 4
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73 m^2
64.389  (19.8024) 108.149  (44.1783) 86.268  (22.1226) 88.251  (30.0118)
17.Secondary Outcome
Title Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B
Hide Description [Not Specified]
Time Frame Part B (MAD): Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449
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Hide 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
Hide 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.
Overall Number of Participants Analyzed 2 8 8 4
Mean (Standard Deviation)
Unit of Measure: percentage change from baseline
Day 29 Number Analyzed 1 participants 7 participants 7 participants 4 participants
9.019 [1]   (NA) -6.672  (11.9614) -0.624  (15.1771) 2.748  (5.6858)
Day 57 Number Analyzed 2 participants 7 participants 8 participants 4 participants
20.184  (23.5572) -8.426  (19.7271) 4.505  (35.2457) 37.030  (56.1210)
Day 85 Number Analyzed 1 participants 8 participants 7 participants 2 participants
-5.945 [1]   (NA) -13.536  (22.8679) -3.720  (22.6231) -6.113  (43.5441)
Day 113 Number Analyzed 0 participants 7 participants 6 participants 4 participants
-14.424  (24.1107) 3.444  (29.6749) 7.570  (40.5928)
Day 141 Number Analyzed 0 participants 7 participants 7 participants 2 participants
-8.804  (27.4802) 9.315  (27.5044) -30.691  (12.8912)
Day 169 Number Analyzed 0 participants 8 participants 7 participants 1 participants
-19.796  (31.7492) -8.544  (14.8481) 20.210 [1]   (NA)
Day 197 Number Analyzed 0 participants 6 participants 7 participants 4 participants
-8.546  (13.5672) -13.513  (25.0560) 28.857  (22.1891)
Day 225 Number Analyzed 0 participants 6 participants 8 participants 3 participants
-18.221  (14.2322) 29.013  (53.5563) -14.964  (9.9130)
Day 253 Number Analyzed 0 participants 6 participants 7 participants 0 participants
-5.140  (19.2839) 10.232  (24.4929)
Day 281 Number Analyzed 0 participants 6 participants 6 participants 0 participants
-14.283  (22.6126) 5.841  (13.0381)
Day 309 Number Analyzed 0 participants 5 participants 4 participants 0 participants
-0.403  (34.6839) 8.441  (11.5329)
Day 337 Number Analyzed 0 participants 4 participants 4 participants 0 participants
-5.168  (31.0756) 8.688  (24.2094)
Day 365 Number Analyzed 0 participants 2 participants 2 participants 0 participants
2.268  (33.7565) 9.201  (14.4856)
Day 393 Number Analyzed 0 participants 3 participants 2 participants 0 participants
-11.942  (45.3027) -4.484  (12.6320)
Day 421 Number Analyzed 0 participants 3 participants 2 participants 0 participants
7.610  (11.2195) -6.498  (12.9022)
Day 449 Number Analyzed 0 participants 0 participants 2 participants 0 participants
-15.093  (10.3705)
[1]
Standard Deviation is not calculated for arms with one participant
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/3 (0.00%)   0/8 (0.00%)   0/8 (0.00%)   0/4 (0.00%) 
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   1/3 (33.33%)   1/8 (12.50%)   3/8 (37.50%)   0/4 (0.00%) 
Gastrointestinal disorders                   
Vomiting  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  2/8 (25.00%)  0/4 (0.00%) 
Abdominal pain  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
General disorders                   
Pyrexia  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Infections and infestations                   
Pyelonephritis acute  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Gastroenteritis  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/4 (0.00%) 
Renal and urinary disorders                   
Nephrolithiasis  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
1
Term from vocabulary, MedDRA (18.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/8 (62.50%)   6/6 (100.00%)   3/6 (50.00%)   6/6 (100.00%)   6/6 (100.00%)   2/3 (66.67%)   7/8 (87.50%)   7/8 (87.50%)   4/4 (100.00%) 
Blood and lymphatic system disorders                   
Lymph node pain  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/4 (0.00%) 
Cardiac disorders                   
Tricuspid valve incompetence  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Congenital, familial and genetic disorders                   
Atrial septal defect  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Eye disorders                   
Visual impairment  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Dry eye  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Eye swelling  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Gastrointestinal disorders                   
Abdominal discomfort  1  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Abdominal pain  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  3/8 (37.50%)  1/4 (25.00%) 
Diarrhoea  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Faeces soft  1  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Flatulence  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Nausea  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Constipation  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  1/8 (12.50%)  0/8 (0.00%)  0/4 (0.00%) 
Toothache  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/4 (0.00%) 
Vomiting  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  1/8 (12.50%)  1/4 (25.00%) 
Abdominal pain upper  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Teething  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
General disorders                   
Fatigue  1  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  2/8 (25.00%)  0/4 (0.00%) 
Injection site pain  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  4/6 (66.67%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Injection site bruising  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/4 (0.00%) 
Injection site erythema  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Injection site pruritus  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Pyrexia  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  1/8 (12.50%)  1/8 (12.50%)  1/4 (25.00%) 
Axillary pain  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Influenza like illness  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/4 (0.00%) 
Injection site discolouration  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Injection site swelling  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Infections and infestations                   
Gastroenteritis  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Influenza  1  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Nasopharyngitis  1  3/8 (37.50%)  1/6 (16.67%)  1/6 (16.67%)  4/6 (66.67%)  4/6 (66.67%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  2/4 (50.00%) 
Periodontitis  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Sinusitis  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Tonsillitis  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Upper respiratory tract infection  1  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/4 (0.00%) 
Urinary tract infection  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/4 (0.00%) 
Viral pharyngitis  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Pharyngitis  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Rhinitis  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  3/8 (37.50%)  0/4 (0.00%) 
Urinary tract infection enterococcal  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Body tinea  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Dermatitis infected  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Urinary tract infection bacterial  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Urinary tract infection staphylococcal  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Injury, poisoning and procedural complications                   
Contusion  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Head injury  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Laceration  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Tendon injury  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Arthropod bite  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Soft tissue injury  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Investigations                   
Alanine aminotransferase increased  1  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Aspartate aminotransferase increased  1  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Blood creatine phosphokinase increased  1  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Blood phosphorus decreased  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Metabolism and nutrition disorders                   
Gout  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Increased appetite  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Overweight  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Musculoskeletal and connective tissue disorders                   
Back pain  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Musculoskeletal chest pain  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Myalgia  1  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Arthralgia  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Groin pain  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Nervous system disorders                   
Headache  1  1/8 (12.50%)  1/6 (16.67%)  2/6 (33.33%)  1/6 (16.67%)  3/6 (50.00%)  0/3 (0.00%)  2/8 (25.00%)  2/8 (25.00%)  0/4 (0.00%) 
Migraine  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Presyncope  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Lethargy  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Psychiatric disorders                   
Alcoholic hangover  1  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Renal and urinary disorders                   
Dysuria  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  1/8 (12.50%)  0/4 (0.00%) 
Nephrolithiasis  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  3/8 (37.50%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders                   
Nasal discomfort  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Oropharyngeal pain  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Cough  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  2/8 (25.00%)  0/4 (0.00%) 
Rhinitis allergic  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Skin and subcutaneous tissue disorders                   
Papule  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Rash follicular  1  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Skin texture abnormal  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Blister  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Rash  1  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/4 (0.00%) 
Social circumstances                   
Caffeine consumption  1  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
1
Term from vocabulary, MedDRA (18.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Alnylam Pharmaceuticals Inc
Phone: 866-330-0326
EMail: Clinicaltrials@alnylam.com
Layout table for additonal information
Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02706886    
Other Study ID Numbers: ALN-GO1-001
2015-004407-23 ( EudraCT Number )
First Submitted: March 3, 2016
First Posted: March 11, 2016
Results First Submitted: January 22, 2020
Results First Posted: January 30, 2020
Last Update Posted: January 30, 2020