Trial Outcomes & Findings for A Study to Evaluate Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1 (NCT NCT04152200)

NCT ID: NCT04152200

Last Updated: 2025-07-18

Results Overview

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. For Cohort A, the baseline was defined as the mean of all plasma oxalate level values collected prior to the first dose of lumasiran.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 21 participants
• Primary outcome timeframe: Baseline to Month 6
• Results posted on: 2025-07-18

Participant Flow

Patients with advanced primary hyperoxaluria type 1 (PH1) were enrolled at thirteen sites in Australia, Belgium, France, Israel, Jordan, Lebanon, the Netherlands, Turkey, the United Arab Emirates and the United States.

Participant milestones

Measure	Cohort A: Lumasiran Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.
Primary Analysis Period STARTED	6	15
Primary Analysis Period COMPLETED	6	15
Primary Analysis Period NOT COMPLETED	0	0
Long-term Extension Period STARTED	6	15
Long-term Extension Period COMPLETED	0	0
Long-term Extension Period NOT COMPLETED	6	15

Reasons for withdrawal

Measure	Cohort A: Lumasiran Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.
Long-term Extension Period Entered Long-term Extension Period after completion of the Primary Analysis Period	6	15

Baseline Characteristics

A Study to Evaluate Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1

Baseline characteristics by cohort

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=15 Participants Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Total n=21 Participants Total of all reporting groups
Age, Continuous	9.0 years n=5 Participants	6.0 years n=7 Participants	8.0 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized White	4 Participants n=5 Participants	12 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	6 Participants n=5 Participants	14 Participants n=7 Participants	20 Participants n=5 Participants
Plasma Oxalate	64.73 μmol/L STANDARD_DEVIATION 41.30 • n=5 Participants	108.35 μmol/L STANDARD_DEVIATION 29.53 • n=7 Participants	95.89 μmol/L STANDARD_DEVIATION 38.01 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Month 6

Population: Full Analysis Set (FAS): All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6.

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. For Cohort A, the baseline was defined as the mean of all plasma oxalate level values collected prior to the first dose of lumasiran.

Outcome measures

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran All patients from Cohorts A and B.
Cohort A: Percent Change in Plasma Oxalate From Baseline to Month 6	-33.33 percent change Standard Error 17.63	—	—

PRIMARY outcome

Timeframe: Baseline to Month 6

Population: FAS: All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6.

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. For Cohort B, the baseline is defined as the mean of the last four pre-dialysis plasma oxalate samples collected prior to the first dose of lumasiran. In Cohort B, only pre-dialysis samples are utilized.

Outcome measures

Measure	Cohort A: Lumasiran n=15 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran All patients from Cohorts A and B.
Cohort B: Percent Change in Pre-dialysis Plasma Oxalate From Baseline to Month 6	-42.43 percent change Standard Error 3.95	—	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS: All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6.

Percent change in plasma oxalate AUC(0-24) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. Baseline was defined as the mean value of all valid AUC (μmol/L/24h) profiles being computed prior to the first dose of lumasiran.

Outcome measures

Measure	Cohort A: Lumasiran n=15 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran All patients from Cohorts A and B.
Cohort B: Percent Change in Plasma Oxalate Area Under the Curve From 0-24 Hours [AUC(0-24)] Between Dialysis Sessions From Baseline to Month 6	-41.4 percent change Standard Error 4.4	—	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS: All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6.

Absolute change in plasma oxalate was estimated by an average absolute change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. For Cohort A, the baseline was defined as the mean of all plasma oxalate level values collected prior to the first dose of lumasiran; for Cohort B, the baseline was defined as the mean of the last 4 pre-dialysis plasma oxalate level values collected prior to the first dose of lumasiran. In Cohort B patients, the plasma oxalate baseline was similarly defined except that the values obtained from the plasma oxalate profile assessment visits only included the pre-dialysis sample collected per visit.

Outcome measures

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=15 Participants Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran All patients from Cohorts A and B.
Absolute Change in Plasma Oxalate From Baseline to Month 6	-35.28 μmol/L Standard Error 7.40	-48.33 μmol/L Standard Error 3.63	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS: All patients who received any amount of lumasiran (with data available for analysis) and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6. No analyses were performed for patients in Cohort B that were anuric (ie, patients able to continue to produce urine ≥100 mL per day).

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. Baseline is defined as the median of all valid 24-hr urine assessments collected prior to the first dose date/time of lumasiran without any non-protocol-related sample issues.

Outcome measures

Measure	Cohort A: Lumasiran n=5 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran All patients from Cohorts A and B.
Cohort A: Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6	-0.533 mmol/24hr/1.73m^2 Standard Error 0.111	—	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS: All patients who received any amount of lumasiran (with data available for analysis) and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6. No analyses were performed for patients in Cohort B that were anuric (ie, patients able to continue to produce urine ≥100 mL per day).

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. Baseline is defined as the mean of all assessments prior to the first dose date/time of lumasiran.

Outcome measures

Measure	Cohort A: Lumasiran n=5 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran All patients from Cohorts A and B.
Cohort A: Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6	-10.557 percent change Standard Error 6.811	—	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS: All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6.

Absolute change in spot urinary oxalate:creatinine ratio was estimated by an average absolute change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. Baseline was defined as the mean of all assessments prior to the first dose date/time of lumasiran.

Outcome measures

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran All patients from Cohorts A and B.
Cohort A: Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6	-0.1879 ratio Standard Error 0.0160	—	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS: All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6.

Percent change in spot urinary oxalate:creatinine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. Baseline was defined as the mean of all assessments prior to the first dose date/time of lumasiran.

Outcome measures

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran All patients from Cohorts A and B.
Cohort A: Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6	-39.5136 percent change Standard Error 9.4294	—	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: Participants from the FAS who were ≥2 to \<18 years of age at the time of consent with data available for analysis.

Peds-QL is a modular approach to measuring quality of life (QOL) in healthy children and adolescents and those with acute and chronic health conditions. The PedsQL Generic Core Scales contain 23 items designed to measure core domains of health (physical, emotional, and social functioning) and role (school functioning). Scores are summarized as Total Scale Score, Physical Health Summary Score, and Psychosocial Health Summary Score. The Total Scale Score will be reported for this study. The PedsQL will be completed by patients (or caregivers, as appropriate) who are ≥2 to <18 years of age at the time of consent. Total score range: 0 - 100, with higher scores indicating better health-related quality of life (HRQoL). Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.

Outcome measures

Measure	Cohort A: Lumasiran n=2 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=5 Participants Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran All patients from Cohorts A and B.
Change in Quality of Life As Assessed by Pediatric Quality of Life Inventory (PedsQL) Total Score From Baseline to Month 6 in Patients >=2 to 18 Years of Age at Time of Informed Consent	-23.91 score on a scale Standard Deviation 9.22	0.10 score on a scale Standard Deviation 8.52	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: Participants from the FAS who were ≥18 years of age at the time of consent.

The KDQOL questionnaire is used to assess 3 core domains of kidney disease including: burden, symptoms/problems, and effects of kidney disease on daily life. The KDQOL subscales (Burden of Kidney Disease, Effect of Kidney Disease on Daily Life, and Symptoms and Problems of Kidney Disease), and the accompanying Short Form-12 (SF-12) Physical Component Summary and Mental Component Summary will be assessed for this study. These will be completed by patients who are ≥18 years of age at the time of consent. Score range (per domain): 0 - 100; higher scores indicate better HRQoL. Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.

Outcome measures

Measure	Cohort A: Lumasiran n=2 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=4 Participants Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran All patients from Cohorts A and B.
Change in Quality of Life As Assessed by Kidney Disease and Quality of Life (KDQOL) Scores From Baseline to Month 6 in Patients ≥18 Years of Age at Time of Informed Consent SF-12 Physical Component Score	-1.56 score on a scale Standard Deviation 1.19	-2.06 score on a scale Standard Deviation 6.59	—
Change in Quality of Life As Assessed by Kidney Disease and Quality of Life (KDQOL) Scores From Baseline to Month 6 in Patients ≥18 Years of Age at Time of Informed Consent SF-12 Mental Component Score	-3.88 score on a scale Standard Deviation 4.45	1.58 score on a scale Standard Deviation 9.61	—
Change in Quality of Life As Assessed by Kidney Disease and Quality of Life (KDQOL) Scores From Baseline to Month 6 in Patients ≥18 Years of Age at Time of Informed Consent Symptoms/Problems of Kidney Disease	-13.64 score on a scale Standard Deviation 6.43	-5.73 score on a scale Standard Deviation 7.49	—
Change in Quality of Life As Assessed by Kidney Disease and Quality of Life (KDQOL) Scores From Baseline to Month 6 in Patients ≥18 Years of Age at Time of Informed Consent Effects of Kidney Disease	-15.63 score on a scale Standard Deviation 22.10	-10.16 score on a scale Standard Deviation 14.96	—
Change in Quality of Life As Assessed by Kidney Disease and Quality of Life (KDQOL) Scores From Baseline to Month 6 in Patients ≥18 Years of Age at Time of Informed Consent Burden of Kidney Disease	-3.13 score on a scale Standard Deviation 4.42	-4.69 score on a scale Standard Deviation 16.44	—

SECONDARY outcome

Timeframe: Day 1; Month 6

Population: Pharmacokinetic (PK) Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data.

Cmax is the highest concentration of lumasiran in the plasma after a dose is given.

Outcome measures

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=15 Participants Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran n=21 Participants All patients from Cohorts A and B.
Maximum Plasma Concentration (Cmax) of Lumasiran Day 1	1019.9 ng/mL Geometric Coefficient of Variation 61.6	1820.5 ng/mL Geometric Coefficient of Variation 113.2	1542.8 ng/mL Geometric Coefficient of Variation 103.7
Maximum Plasma Concentration (Cmax) of Lumasiran Month 6	1038.2 ng/mL Geometric Coefficient of Variation 36.9	1289.3 ng/mL Geometric Coefficient of Variation 106.0	1211.9 ng/mL Geometric Coefficient of Variation 87.6

SECONDARY outcome

Timeframe: Day 1; Month 6

Population: PK Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data.

Tmax is the time it takes for lumasiran to reach the maximum concentration (Cmax) after administration.

Outcome measures

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=15 Participants Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran n=21 Participants All patients from Cohorts A and B.
Time to Maximum Plasma Concentration (Tmax) of Lumasiran Day 1	3.8083 hours Interval 1.767 to 11.533	4.0000 hours Interval 1.717 to 12.0	4.0000 hours Interval 1.717 to 12.0
Time to Maximum Plasma Concentration (Tmax) of Lumasiran Month 6	3.9083 hours Interval 1.983 to 7.617	4.0167 hours Interval 1.967 to 12.0	4.0000 hours Interval 1.967 to 12.0

SECONDARY outcome

Timeframe: Day 1; Month 6

Population: PK Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data at the given timepoint.

t½β is the time it takes for the concentration of the drug in the plasma to be reduced by 50%.

Outcome measures

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=15 Participants Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran n=21 Participants All patients from Cohorts A and B.
Elimination Half-life (t½β) of Lumasiran Day 1	9.0246 hours Interval 3.364 to 10.593	3.6670 hours Interval 1.127 to 7.793	3.8302 hours Interval 1.127 to 10.593
Elimination Half-life (t½β) of Lumasiran Month 6	8.1069 hours Interval 2.42 to 10.796	4.5131 hours Interval 1.388 to 7.354	5.7484 hours Interval 1.388 to 10.796

SECONDARY outcome

Timeframe: Day 1; Month 6

Population: PK Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data at the given timepoint.

AUC(0-24) is the area under the plasma concentration-time curve over the last 24-h dosing interval.

Outcome measures

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=15 Participants Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran n=21 Participants All patients from Cohorts A and B.
Area Under the Concentration-time Curve From 0 to 24 Hours [AUC(0-24)] for Lumasiran Day 1	13156.8031 h*ng/mL Geometric Coefficient of Variation 64.6	13170.3716 h*ng/mL Geometric Coefficient of Variation 35.6	13164.1075 h*ng/mL Geometric Coefficient of Variation 47.7
Area Under the Concentration-time Curve From 0 to 24 Hours [AUC(0-24)] for Lumasiran Month 6	11417.0267 h*ng/mL Geometric Coefficient of Variation 33.5	20647.6317 h*ng/mL Geometric Coefficient of Variation 61.6	14856.4905 h*ng/mL Geometric Coefficient of Variation 55.9

SECONDARY outcome

Timeframe: Day 1; Month 6

Population: PK Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data at the given timepoint.

CL/F is the rate at which lumasiran is eliminated from the body.

Outcome measures

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=15 Participants Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran n=21 Participants All patients from Cohorts A and B.
Apparent Clearance (CL/F) of Lumasiran Day 1	7.8440 Liters/hour (L/h) Geometric Coefficient of Variation 105.5	5.1003 Liters/hour (L/h) Geometric Coefficient of Variation 77.7	5.7356 Liters/hour (L/h) Geometric Coefficient of Variation 82.6
Apparent Clearance (CL/F) of Lumasiran Month 6	4.8496 Liters/hour (L/h) Geometric Coefficient of Variation 112.8	6.8556 Liters/hour (L/h) Geometric Coefficient of Variation 44.8	5.9104 Liters/hour (L/h) Geometric Coefficient of Variation 70.1

SECONDARY outcome

Timeframe: Day 1; Month 6

Population: PK Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data at the given timepoint.

V/F is the propensity of lumasiran to either remain in the plasma or redistribute to other tissues.

Outcome measures

Measure	Cohort A: Lumasiran n=6 Participants Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=15 Participants Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	All Lumasiran n=21 Participants All patients from Cohorts A and B.
Apparent Volume of Distribution (V/F) of Lumasiran Day 1	77.5329 Liters (L) Geometric Coefficient of Variation 91.1	25.7429 Liters (L) Geometric Coefficient of Variation 196.4	34.7734 Liters (L) Geometric Coefficient of Variation 185.7
Apparent Volume of Distribution (V/F) of Lumasiran Month 6	41.7081 Liters (L) Geometric Coefficient of Variation 229.3	36.8305 Liters (L) Geometric Coefficient of Variation 166.9	38.8468 Liters (L) Geometric Coefficient of Variation 161.3

SECONDARY outcome

Timeframe: Baseline to Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Peds-QL is a modular approach to measuring quality of life (QOL) in healthy children and adolescents and those with acute and chronic health conditions. The PedsQL Generic Core Scales contain 23 items designed to measure core domains of health (physical, emotional, and social functioning) and role (school functioning). Scores are summarized as Total Scale Score, Physical Health Summary Score, and Psychosocial Health Summary Score. The Total Scale Score will be reported for this study. The PedsQL will be completed by patients (or caregivers, as appropriate) who are ≥2 to <18 years of age at the time of consent. Total score range: 0 - 100, with higher scores indicating better health-related quality of life (HRQoL). Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

The KDQOL questionnaire is used to assess 3 core domains of kidney disease including: burden, symptoms/problems, and effects of kidney disease on daily life. The KDQOL subscales (Burden of Kidney Disease, Effect of Kidney Disease on Daily Life, and Symptoms and Problems of Kidney Disease), and the accompanying Short Form-12 (SF-12) Physical Component Summary and Mental Component Summary will be assessed for this study. These will be completed by patients who are ≥18 years of age at the time of consent. Score range (per domain): 0 - 100; higher scores indicate better HRQoL. Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Nephrocalcinosis will be assessed by renal ultrasound.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Modes of dialysis are defined as hemodialysis and peritoneal dialysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 60

Systemic oxalosis will be assessed in cardiac, skeletal, ophthalmologic, and dermatologic systems.

Outcome measures

Outcome data not reported

Adverse Events

Cohort A: Lumasiran

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort B: Lumasiran

Serious events: 8 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cohort A: Lumasiran n=6 participants at risk Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=15 participants at risk Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Blood and lymphatic system disorders Spontaneous haematoma	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Gastrointestinal disorders Pancreatitis	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Gastrointestinal disorders Vomiting	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
General disorders Catheter site swelling	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
General disorders Device related thrombosis	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
General disorders Pyrexia	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Device related infection	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	13.3% 2/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Injury, poisoning and procedural complications Skin scar contracture	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Investigations General physical condition abnormal	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Metabolism and nutrition disorders Hypokalaemia	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Nervous system disorders Seizure	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Surgical and medical procedures Arteriovenous fistula operation	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Surgical and medical procedures Dialysis device insertion	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Surgical and medical procedures Renal and liver transplant	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Surgical and medical procedures Renal transplant	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	13.3% 2/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Vascular disorders Haemorrhage	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.

Other adverse events

Measure	Cohort A: Lumasiran n=6 participants at risk Patients not on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.	Cohort B: Lumasiran n=15 participants at risk Patients on dialysis received open-label lumasiran based on weight. Patients weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from \<10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to \<20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached.
Blood and lymphatic system disorders Blood loss anaemia	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Endocrine disorders Hyperparathyroidism tertiary	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Gastrointestinal disorders Constipation	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	20.0% 3/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Gastrointestinal disorders Gastritis	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Gastrointestinal disorders Peptic ulcer	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
General disorders Injection site reaction	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	26.7% 4/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
General disorders Pyrexia	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	40.0% 6/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
General disorders Swelling	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Hepatobiliary disorders Cholelithiasis	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Candida nappy rash	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Catheter site infection	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Clostridium difficile colitis	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Conjunctivitis	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Device related infection	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	13.3% 2/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Ear infection	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Paronychia	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Roseola	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Sepsis	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Upper respiratory tract infection	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Infections and infestations Urinary tract infection	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Injury, poisoning and procedural complications Burns second degree	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Injury, poisoning and procedural complications Head injury	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Injury, poisoning and procedural complications Limb injury	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Injury, poisoning and procedural complications Upper limb fracture	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Investigations Alanine aminotransferase increased	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Investigations Aspartate aminotransferase increased	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Investigations Blood phosphorus increased	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Investigations Blood potassium increased	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Investigations Blood uric acid increased	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Investigations International normalised ratio increased	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Investigations Liver function test increased	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Investigations SARS-CoV-2 test positive	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	13.3% 2/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Investigations Staphylococcus test positive	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Metabolism and nutrition disorders Carnitine deficiency	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Metabolism and nutrition disorders Hyperkalaemia	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Metabolism and nutrition disorders Iron deficiency	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Metabolism and nutrition disorders Metabolic acidosis	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Metabolism and nutrition disorders Vitamin D deficiency	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Nervous system disorders Paraesthesia	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Product Issues Thrombosis in device	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Psychiatric disorders Insomnia	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Renal and urinary disorders Proteinuria	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Renal and urinary disorders Renal impairment	16.7% 1/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	0.00% 0/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Vascular disorders Dialysis hypotension	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Vascular disorders Hypotension	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.
Vascular disorders Jugular vein thrombosis	0.00% 0/6 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.	6.7% 1/15 • Non-serious adverse events (AEs) are reported from the administration of the first dose of study drug up to approximately 6 months. Serious adverse events (SAEs) are reported from the time when the informed consent is signed up to approximately 6 months.

Additional Information

Chief Medical Officer

Alnylam Pharmaceuticals Inc.

Phone: 866-330-0326

Email: clinicaltrials@alnylam.com

Results disclosure agreements

• Principal investigator is a sponsor employee 1. Copy of disclosure is provided to Sponsor at least 60 days before submission for publication or date of disclosure 2. Confidential information is deleted if requested by Sponsor 3. If a Discovery is disclosed, defer publication or disclosure for 60 days from time Sponsor notifies them of its wish to file a patent application on such Discovery 4. Site/Investigator will not disclose or publish results until results from all sites have been received and analyzed by Sponsor
• Publication restrictions are in place

Restriction type: OTHER