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A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1 (ILLUMINATE-A)

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ClinicalTrials.gov Identifier: NCT03681184
Recruitment Status : Active, not recruiting
First Posted : September 21, 2018
Results First Posted : January 19, 2021
Last Update Posted : May 16, 2022
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Primary Hyperoxaluria Type 1 (PH1)
Interventions Drug: Placebo
Drug: Lumasiran
Enrollment 39
Recruitment Details Participants with primary hyperoxaluria type 1 (PH1) were enrolled at sixteen sites in France, Germany, Israel, the Netherlands, Switzerland, the United Arab Emirates, the United Kingdom and the United States.
Pre-assignment Details  
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period. Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Period Title: 6-Month Double-Blind Period
Started 13 26
Completed 13 25
Not Completed 0 1
Reason Not Completed
Parent/Caregiver Withdrew Consent             0             1
Period Title: 3-Month Blinded Extension Period
Started 13 24 [1]
Completed 1 1
Not Completed 12 23
Reason Not Completed
Remained in this Period at Time of Data Cut             12             23
[1]
1 participant discontinued study drug and entered safety follow up after the DB period.
Period Title: Open-Label Extension Period
Started 1 1
Completed 0 0
Not Completed 1 1
Reason Not Completed
Remained in this Period at Time of Data Cut             1             1
Arm/Group Title Placebo Lumasiran Total
Hide Arm/Group Description Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period. Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period. Total of all reporting groups
Overall Number of Baseline Participants 13 26 39
Hide Baseline Analysis Population Description
Full Analysis Set (FAS): All randomized patients who received any amount of study drug, was used for all baseline characteristics, except for 24-hour urinary oxalate excretion corrected for body surface area (BSA), which used the Safety Analysis Set (SAS): All participants who received any amount of study drug.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 26 participants 39 participants
6 to <12 Years
7
  53.8%
9
  34.6%
16
  41.0%
12 to <18 Years
1
   7.7%
5
  19.2%
6
  15.4%
18 to <65 Years
5
  38.5%
12
  46.2%
17
  43.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 26 participants 39 participants
Female
5
  38.5%
8
  30.8%
13
  33.3%
Male
8
  61.5%
18
  69.2%
26
  66.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 26 participants 39 participants
Asian
3
  23.1%
3
  11.5%
6
  15.4%
White
9
  69.2%
21
  80.8%
30
  76.9%
Other
0
   0.0%
2
   7.7%
2
   5.1%
More than one race
1
   7.7%
0
   0.0%
1
   2.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 26 participants 39 participants
Hispanic or Latino
0
   0.0%
1
   3.8%
1
   2.6%
Not Hispanic or Latino
13
 100.0%
25
  96.2%
38
  97.4%
Age at Informed Consent  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 26 participants 39 participants
17.0  (15.19) 18.7  (11.52) 18.1  (12.68)
24-Hour Urinary Oxalate Excretion Corrected for BSA  
Mean (Standard Deviation)
Unit of measure:  Mmol/24hr/1.73m^2
Number Analyzed 13 participants 26 participants 39 participants
1.79  (0.68) 1.83  (0.60) 1.82  (0.62)
1.Primary Outcome
Title Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
Hide Description Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized patients who received any amount of study drug.
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description:
Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Overall Number of Participants Analyzed 13 26
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-11.8  (3.8) -65.4  (2.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lumasiran
Comments The Mixed-Effect Model Repeated Measures (MMRM) includes fixed effects of treatment arms (lumasiran vs. placebo) and scheduled visits (months 3, 4, 5, and 6), baseline 24-hour urinary oxalate corrected for BSA as a continuous fixed covariate, and patient as a random effect. The variance-covariance matrix is assumed to be unstructured. Satterthwaite approximation is used to estimate denominator degrees of freedom.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P=1.685E-14
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares (LS) Mean
Estimated Value -53.546
Confidence Interval (2-Sided) 95%
-62.314 to -44.778
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.3224
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6
Hide Description Absolute change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average absolute change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized patients who received any amount of study drug.
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description:
Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Overall Number of Participants Analyzed 13 26
Least Squares Mean (Standard Error)
Unit of Measure: mmol/24hr/1.73m^2
-0.27  (0.08) -1.24  (0.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lumasiran
Comments The MMRM includes fixed effects of treatment arms (lumasiran vs. placebo) and scheduled visits (months 3, 4, 5, and 6), baseline 24-hour urinary oxalate corrected for BSA as a continuous fixed covariate, and patient as a random effect. The variance-covariance matrix is assumed to be unstructured. Satterthwaite approximation is used to estimate denominator degrees of freedom.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P=1.225E-11
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Mean
Estimated Value -0.975
Confidence Interval (2-Sided) 95%
-1.177 to -0.772
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0998
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
Hide Description Percent change in 24-hour urinary oxalate:creatine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized patients who received any amount of study drug.
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description:
Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Overall Number of Participants Analyzed 13 26
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-10.8  (5.4) -62.5  (4.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lumasiran
Comments The MMRM includes fixed effects of treatment arms (lumasiran vs. placebo) and scheduled visits (months 3, 4, 5, and 6), baseline 24-hour urinary oxalate:creatinine ratio as a continuous fixed covariate, and patient as a random effect. The variance-covariance matrix is assumed to be unstructured. Satterthwaite approximation is used to estimate denominator degrees of freedom.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P=5.032E-10
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Mean
Estimated Value -51.7718
Confidence Interval (2-Sided) 95%
-64.2653 to -39.2784
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.16118
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6
Hide Description The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the FAS (all randomized patients who received any amount of study drug) for whom data are available.
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description:
Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Overall Number of Participants Analyzed 13 25
Measure Type: Number
Unit of Measure: percentage of participants
0 84
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lumasiran
Comments The proportion of participants (lumasiran vs. placebo) with 24-hour urinary oxalate ≤1.5 x ULN at Month 6 is analyzed using the Cochran-Mantel-Haenszel test, stratified by baseline 24-hour urinary oxalate corrected for BSA (≤1.70 mmol/24hr/1.73m^2 vs. >1.70 mmol/24hr/1.73m^2). The difference in proportion (lumasiran vs. placebo) and the corresponding 95% confidence interval are calculated using the Newcombe method, based on the Wilson score.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P=8.341E-07
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Proportions
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.55 to 0.94
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6
Hide Description The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the FAS (all randomized patients who received any amount of study drug) for whom data are available.
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description:
Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Overall Number of Participants Analyzed 13 25
Measure Type: Number
Unit of Measure: percentage of participants
0 52
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lumasiran
Comments The proportion of participants (lumasiran vs. placebo) with 24-hour urinary oxalate ≤ULN at Month 6 is analyzed using the Cochran-Mantel-Haenszel test, stratified by baseline 24-hour urinary oxalate corrected for BSA (≤1.70 mmol/24hr/1.73m^2 vs. >1.70 mmol/24hr/1.73m^2). The difference in proportion (lumasiran vs. placebo) and the corresponding 95% confidence interval are calculated using the Newcombe method, based on the Wilson score.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Proportions
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.23 to 0.70
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage Change in Plasma Oxalate From Baseline to Month 6
Hide Description Percent change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Plasma Oxalate Analysis Set: all participants who received any amount of study drug and had baseline plasma oxalate level ≥1.5×lower limit of quantitation (LLOQ). LLOQ is 5.55 μmol/L.
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description:
Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Overall Number of Participants Analyzed 10 23
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.3  (4.3) -39.8  (2.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lumasiran
Comments The MMRM includes fixed effects of treatment arms (lumasiran vs. placebo) and scheduled visits (months 3, 4, 5, and 6), baseline plasma oxalate as a continuous fixed covariate, and patient as a random effect. The variance-covariance matrix is assumed to be unstructured. Satterthwaite approximation is used to estimate denominator degrees of freedom.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P=2.862E-08
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Mean
Estimated Value -39.48
Confidence Interval (2-Sided) 95%
-50.10 to -28.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.181
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Absolute Change in Plasma Oxalate From Baseline to Month 6
Hide Description Absolute change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Plasma Oxalate Analysis Set: all participants who received any amount of study drug and had baseline plasma oxalate level ≥1.5×LLOQ. LLOQ is 5.55 μmol/L.
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description:
Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Overall Number of Participants Analyzed 10 23
Least Squares Mean (Standard Error)
Unit of Measure: μmol/L
1.3  (1.1) -7.5  (0.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lumasiran
Comments The MMRM includes fixed effects of treatment arms (lumasiran vs. placebo) and scheduled visits (months 3, 4, 5, and 6), baseline plasma oxalate as a continuous fixed covariate, and patient as a random effect. The variance-covariance matrix is assumed to be unstructured. Satterthwaite approximation is used to estimate denominator degrees of freedom.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P=3.893E-07
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Mean
Estimated Value -8.71
Confidence Interval (2-Sided) 95%
-11.45 to -5.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.338
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6
Hide Description eGFR is calculated from serum creatinine based on the Modification of Diet in Renal Disease formula for patients ≥18 years of age and the Schwartz Bedside Formula for patients <18 years of age at screening. Change from baseline to Month 6 is reported.
Time Frame Baseline, Week 2, Months 1, 2, 3, 4, 5 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the FAS (all randomized patients who received any amount of study drug) for whom data are available.
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description:
Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Overall Number of Participants Analyzed 13 26
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
Week 2 Number Analyzed 13 participants 24 participants
-5  (9) -4  (9)
Month 1 Number Analyzed 12 participants 25 participants
-6  (7) -2  (12)
Month 2 Number Analyzed 13 participants 25 participants
-5  (8) -2  (15)
Month 3 Number Analyzed 13 participants 25 participants
-3  (6) 0  (11)
Month 4 Number Analyzed 12 participants 25 participants
-4  (8) -4  (10)
Month 5 Number Analyzed 13 participants 25 participants
-4  (7) -6  (13)
Month 6 Number Analyzed 13 participants 25 participants
0  (6) -3  (11)
9.Secondary Outcome
Title Absolute Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period
Hide Description [Not Specified]
Time Frame Up to 60 months
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Percentage Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period
Hide Description [Not Specified]
Time Frame Up to 60 months
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During the Extension Period
Hide Description [Not Specified]
Time Frame Up to 60 months
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline Over Time During the Extension Period
Hide Description [Not Specified]
Time Frame Up to 60 months
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time During the Extension Period
Hide Description [Not Specified]
Time Frame Up to 60 months
Outcome Measure Data Not Reported
14.Other Pre-specified Outcome
Title Rate of Renal Stone Events
Hide Description A renal stone event is defined as a patient-reported event that includes ≥1 of the following: visit to healthcare provider because of a renal stone; medication for renal colic; stone passage; macroscopic hematuria due to a renal stone. Lower rates indicate a favorable outcome.
Time Frame 12-Month Period prior to Informed Consent, 6-Month DB Period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized patients who received any amount of study drug.
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description:
Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Overall Number of Participants Analyzed 13 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Rate per person-year
12-Month Period prior to Informed Consent
0.54
(0.26 to 1.13)
3.19
(2.57 to 3.96)
6-Month DB Period
0.66
(0.25 to 1.76)
1.09
(0.63 to 1.87)
15.Other Pre-specified Outcome
Title Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound
Hide Description Renal ultrasound data were used to grade medullary nephrocalcinosis findings (range: 0 to 3), where a higher grade indicates greater severity. Improving=if both sides improve, or one side improves and the other side has no change; No change=if both sides have no change; Worsening=if both sides worsen, or one side worsens and the other side has no change; Indeterminate=if one side improves and the other side worsens.
Time Frame Baseline, Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the FAS (all randomized patients who received any amount of study drug) with both Baseline and Month 6 renal ultrasounds.
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description:
Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Overall Number of Participants Analyzed 12 22
Measure Type: Count of Participants
Unit of Measure: Participants
Improving
0
   0.0%
3
  13.6%
No Change
11
  91.7%
19
  86.4%
Worsening
1
   8.3%
0
   0.0%
Indeterminate
0
   0.0%
0
   0.0%
Time Frame From the first dose of study drug through the 6-Month DB Period.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Lumasiran
Hide Arm/Group Description Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period. Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
All-Cause Mortality
Placebo Lumasiran
Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)   0/26 (0.00%) 
Hide Serious Adverse Events
Placebo Lumasiran
Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)   0/26 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Lumasiran
Affected / at Risk (%) Affected / at Risk (%)
Total   9/13 (69.23%)   14/26 (53.85%) 
Gastrointestinal disorders     
Abdominal discomfort  1  1/13 (7.69%)  1/26 (3.85%) 
Abdominal pain  1  0/13 (0.00%)  2/26 (7.69%) 
Abdominal pain upper  1  0/13 (0.00%)  2/26 (7.69%) 
General disorders     
Injection site erythema  1  0/13 (0.00%)  3/26 (11.54%) 
Injection site pain  1  0/13 (0.00%)  3/26 (11.54%) 
Injection site reaction  1  0/13 (0.00%)  6/26 (23.08%) 
Infections and infestations     
Otitis media acute  1  1/13 (7.69%)  0/26 (0.00%) 
Pneumonia  1  0/13 (0.00%)  2/26 (7.69%) 
Rhinitis  1  2/13 (15.38%)  2/26 (7.69%) 
Tooth infection  1  1/13 (7.69%)  0/26 (0.00%) 
Upper respiratory tract infection  1  2/13 (15.38%)  2/26 (7.69%) 
Urinary tract infection  1  0/13 (0.00%)  2/26 (7.69%) 
Injury, poisoning and procedural complications     
Contusion  1  1/13 (7.69%)  0/26 (0.00%) 
Gastrostomy tube site complication  1  1/13 (7.69%)  0/26 (0.00%) 
Metabolism and nutrition disorders     
Iron deficiency  1  1/13 (7.69%)  0/26 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/13 (7.69%)  2/26 (7.69%) 
Pain in extremity  1  1/13 (7.69%)  0/26 (0.00%) 
Nervous system disorders     
Headache  1  3/13 (23.08%)  3/26 (11.54%) 
Respiratory, thoracic and mediastinal disorders     
Nasal congestion  1  1/13 (7.69%)  1/26 (3.85%) 
Oropharyngeal pain  1  1/13 (7.69%)  1/26 (3.85%) 
1
Term from vocabulary, MedDRA (21.1)
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: NCT03681184    
Other Study ID Numbers: ALN-GO1-003
2018-001981-40 ( EudraCT Number )
First Submitted: September 19, 2018
First Posted: September 21, 2018
Results First Submitted: December 22, 2020
Results First Posted: January 19, 2021
Last Update Posted: May 16, 2022