Trial Outcomes & Findings for A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1 (NCT NCT03681184)

Last Updated: 2024-08-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

39 participants

Primary outcome timeframe

Baseline to Month 6

Results posted on

2024-08-12

Participant Flow

Participants with PH1 were enrolled at sixteen sites in France, Germany, Israel, the Netherlands, Switzerland, the United Arab Emirates, the United Kingdom and the United States.

Participants were treated with placebo or lumasiran during the 6-month Double-Blind (DB) Period. All participants received lumasiran during the 3-Month Blinded Treatment Extension Period and 51-Month Open-Label Extension Period.

Participant milestones

Participant milestones
Measure	Placebo/Lumasiran Lumasiran-matching placebo (normal saline \[0.9% NaCl\]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
6-Month Double-Blind Period STARTED	13	26
6-Month Double-Blind Period COMPLETED	13	25
6-Month Double-Blind Period NOT COMPLETED	0	1
3-Month Blinded Extension Period STARTED	13	24
3-Month Blinded Extension Period COMPLETED	13	24
3-Month Blinded Extension Period NOT COMPLETED	0	0
Open-Label Extension Period STARTED	13	24
Open-Label Extension Period COMPLETED	13	24
Open-Label Extension Period NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Lumasiran Lumasiran-matching placebo (normal saline \[0.9% NaCl\]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
6-Month Double-Blind Period Parent/Caregiver Withdrew Consent	0	1

Baseline Characteristics

A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Lumasiran n=13 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=26 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Total n=39 Participants Total of all reporting groups
Age, Customized 6 to <12 Years	7 Participants n=99 Participants	9 Participants n=107 Participants	16 Participants n=206 Participants
Age, Customized 12 to <18 Years	1 Participants n=99 Participants	5 Participants n=107 Participants	6 Participants n=206 Participants
Age, Customized 18 to <65 Years	5 Participants n=99 Participants	12 Participants n=107 Participants	17 Participants n=206 Participants
Sex: Female, Male Female	5 Participants n=99 Participants	8 Participants n=107 Participants	13 Participants n=206 Participants
Sex: Female, Male Male	8 Participants n=99 Participants	18 Participants n=107 Participants	26 Participants n=206 Participants
Race/Ethnicity, Customized Asian	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Race/Ethnicity, Customized White	9 Participants n=99 Participants	21 Participants n=107 Participants	30 Participants n=206 Participants
Race/Ethnicity, Customized Other	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Race/Ethnicity, Customized More than one race	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	13 Participants n=99 Participants	25 Participants n=107 Participants	38 Participants n=206 Participants
Age at Informed Consent	17.0 years STANDARD_DEVIATION 15.19 • n=99 Participants	18.7 years STANDARD_DEVIATION 11.52 • n=107 Participants	18.1 years STANDARD_DEVIATION 12.68 • n=206 Participants
24-Hour Urinary Oxalate Excretion Corrected for BSA	1.79 mmol/24hr/1.73m^2 STANDARD_DEVIATION 0.68 • n=99 Participants	1.83 mmol/24hr/1.73m^2 STANDARD_DEVIATION 0.60 • n=107 Participants	1.82 mmol/24hr/1.73m^2 STANDARD_DEVIATION 0.62 • n=206 Participants
Estimated Glomerular Filtration Rate (eGFR)	78.834 mL/min/1.73m^2 STANDARD_DEVIATION 29.9841 • n=99 Participants	82.967 mL/min/1.73m^2 STANDARD_DEVIATION 25.5499 • n=107 Participants	81.589 mL/min/1.73m^2 STANDARD_DEVIATION 26.7820 • n=206 Participants
24-hour Urinary Oxalate:Creatinine Ratio	0.231 mmol/mmol STANDARD_DEVIATION 0.1306 • n=99 Participants	0.209 mmol/mmol STANDARD_DEVIATION 0.1012 • n=107 Participants	0.216 mmol/mmol STANDARD_DEVIATION 0.1106 • n=206 Participants

PRIMARY outcome

Timeframe: Baseline to Month 6

Population: FAS: All randomized participants who received any amount of study drug.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=13 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=26 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6	-11.8 percent change Standard Error 3.8	-65.4 percent change Standard Error 2.9	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS: All randomized participants who received any amount of study drug.

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.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=13 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=26 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6	-0.27 mmol/24hr/1.73m^2 Standard Error 0.08	-1.24 mmol/24hr/1.73m^2 Standard Error 0.06	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS: All randomized participants who received any amount of study drug.

Percent change in 24-hour urinary oxalate:creatine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=13 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=26 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6	-10.8 percent change Standard Error 5.4	-62.5 percent change Standard Error 4.0	—

SECONDARY outcome

Timeframe: Month 6

Population: Participants from the FAS (all randomized participants who received any amount of study drug) for whom data are available.

The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m\^2 for 24-hour urinary oxalate excretion corrected for BSA.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=13 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=25 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6	0 percentage of participants	84.0 percentage of participants	—

SECONDARY outcome

Timeframe: Month 6

Population: Participants from the FAS (all randomized participants who received any amount of study drug) for whom data are available.

The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m\^2 for 24-hour urinary oxalate excretion corrected for BSA.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=13 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=25 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6	0 percentage of participants	52.0 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: Plasma Oxalate Analysis Set: all participants who received any amount of study drug and had baseline plasma oxalate level ≥1.5×lower limit of quantitation (LLOQ). LLOQ is 5.55 μmol/L.

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.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=10 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=23 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Percentage Change in Plasma Oxalate From Baseline to Month 6	-0.3 percent change Standard Error 4.3	-39.8 percent change Standard Error 2.9	—

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: Plasma Oxalate Analysis Set: all participants who received any amount of study drug and had baseline plasma oxalate level ≥1.5×LLOQ. LLOQ is 5.55 μmol/L.

Absolute change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=10 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=23 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Absolute Change in Plasma Oxalate From Baseline to Month 6	1.3 μmol/L Standard Error 1.1	-7.5 μmol/L Standard Error 0.8	—

SECONDARY outcome

Timeframe: Baseline, Week 2, Months 1, 2, 3, 4, 5 and 6

Population: Participants from the FAS (all randomized participants who received any amount of study drug) for whom data are available.

eGFR is calculated from serum creatinine based on the Modification of Diet in Renal Disease formula for patients ≥18 years of age and the Schwartz Bedside Formula for patients \>1 year to \<18 years of age at screening. Change from baseline to Month 6 is reported.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=13 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=25 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6 Month 1	-6 mL/min/1.73m^2 Standard Deviation 7	-2 mL/min/1.73m^2 Standard Deviation 12	—
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6 Month 2	-5 mL/min/1.73m^2 Standard Deviation 8	-2 mL/min/1.73m^2 Standard Deviation 15	—
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6 Week 2	-5 mL/min/1.73m^2 Standard Deviation 9	-4 mL/min/1.73m^2 Standard Deviation 9	—
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6 Month 3	-3 mL/min/1.73m^2 Standard Deviation 6	0 mL/min/1.73m^2 Standard Deviation 11	—
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6 Month 4	-4 mL/min/1.73m^2 Standard Deviation 8	-4 mL/min/1.73m^2 Standard Deviation 10	—
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6 Month 5	-4 mL/min/1.73m^2 Standard Deviation 7	-6 mL/min/1.73m^2 Standard Deviation 13	—
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6 Month 6	0 mL/min/1.73m^2 Standard Deviation 6	-3 mL/min/1.73m^2 Standard Deviation 11	—

SECONDARY outcome

Timeframe: From Baseline to Month 54 and Month 60

Population: All Lumasiran Treated Set: All participants who received any amount of lumasiran including participants who took lumasiran during the 6-month double-blinded period and participants who initially took placebo during the 6-month double-blinded period and then switched to lumasiran during the extension period. Overall number analyzed is number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Absolute change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average absolute change from baseline in the extension periods. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=6 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=23 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for BSA From Baseline in the Extension Period At Month 54	-0.951 mmol/24hr/1.73m^2 Standard Deviation 0.6148	-1.086 mmol/24hr/1.73m^2 Standard Deviation 0.7678	—
Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for BSA From Baseline in the Extension Period At Month 60	—	-1.129 mmol/24hr/1.73m^2 Standard Deviation 0.7581	—

SECONDARY outcome

Timeframe: From Baseline to Month 54 and Month 60

Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline in the extension periods. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=6 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=23 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Percentage Change in 24-hour Urinary Oxalate Excretion Corrected by BSA From Baseline in the Extension Period At Month 54	-55.57 percent change Standard Deviation 11.903	-53.87 percent change Standard Deviation 41.919	—
Percentage Change in 24-hour Urinary Oxalate Excretion Corrected by BSA From Baseline in the Extension Period At Month 60	—	-53.98 percent change Standard Deviation 28.476	—

SECONDARY outcome

Timeframe: Up to Month 60

The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m\^2 for 24-hour urinary oxalate excretion corrected for BSA.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=13 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=26 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During Lumasiran Treatment	89.44 percentage of time Interval 21.1 to 99.3	89.23 percentage of time Interval 1.7 to 98.6	—

SECONDARY outcome

Timeframe: From Baseline to Month 54 and Month 60

Absolute change in 24-hour urinary oxalate:creatinine ratio was estimated by an average absolute change from baseline to the end of the OLE period at Month 54 and Month 60. A negative change from Baseline indicates a favorable outcome.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=6 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=24 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Absolute Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline in the Extension Period At Month 54	-0.145 mmol/mmol Standard Deviation 0.1242	-0.127 mmol/mmol Standard Deviation 0.1063	—
Absolute Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline in the Extension Period At Month 60	—	-0.138 mmol/mmol Standard Deviation 0.1162	—

SECONDARY outcome

Timeframe: From Baseline to Month 54 and Month 60

Population: All Lumasiran Treated Set: All participants who received any amount of lumasiran including participants who took lumasiran during the 6-month double-blinded period and participants who initially took placebo during the 6-month double-blinded period and then switched to lumasiran during the extension period. Overall number analyzed is number of participants with data available for analysis. Number analysed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=6 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=23 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline in the Extension Period At Month 54	-12.860 mL/min/1.73m^2 Standard Deviation 9.5386	-6.899 mL/min/1.73m^2 Standard Deviation 12.9302	—
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline in the Extension Period At Month 60	—	-2.892 mL/min/1.73m^2 Standard Deviation 11.6544	—

SECONDARY outcome

Timeframe: DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60).

Population: Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.

An AE is any untoward medical occurrence in a clinical investigational participant administered a medicinal product \& which does not necessarily have a causal relationship with this treatment. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization/prolongation of existing hospitalization, results in persistent/significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event that may not be immediately life-threatening/result in death/hospitalization but may jeopardize the participant \& may require intervention to prevent one of the other outcomes listed above. All Lumasiran Treated Set: All participants who received any amount of lumasiran including participants who took lumasiran during 6-month double-blinded period \& participants who initially took placebo during the 6-month double-blinded period and then switched to lumasiran during the extension period.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=13 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=13 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=26 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Event (AE)	9 Participants	12 Participants	25 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious Adverse Event (SAE)	0 Participants	1 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 12-Month Period prior to Informed Consent, 6-Month DB Period

Population: FAS: All randomized participants who received any amount of study drug.

A renal stone event is defined as a patient-reported event that includes ≥1 of the following: visit to healthcare provider because of a renal stone; medication for renal colic; stone passage; macroscopic hematuria due to a renal stone. Lower rates indicate a favorable outcome.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=13 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=26 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Rate of Renal Stone Events 12-Month Period prior to Informed Consent	0.54 events per person-year Interval 0.26 to 1.13	3.19 events per person-year Interval 2.57 to 3.96	—
Rate of Renal Stone Events 6-Month DB Period	0.66 events per person-year Interval 0.25 to 1.76	1.09 events per person-year Interval 0.63 to 1.87	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 6

Population: Participants from the FAS (all randomized participants who received any amount of study drug) with both Baseline and Month 6 renal ultrasounds.

Renal ultrasound data were used to grade medullary nephrocalcinosis findings (range: 0 to 3), where a higher grade indicates greater severity. Improving=if both sides improve, or one side improves and the other side has no change; No change=if both sides have no change; Worsening=if both sides worsen, or one side worsens and the other side has no change; Indeterminate=if one side improves and the other side worsens.

Outcome measures

Outcome measures
Measure	Placebo/Lumasiran n=12 Participants Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=22 Participants Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound Improving	0 Participants	3 Participants	—
Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound No Change	11 Participants	19 Participants	—
Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound Worsening	1 Participants	0 Participants	—
Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound Indeterminate	0 Participants	0 Participants	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo/Lumasiran

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Lumasiran/Lumasiran

Serious events: 5 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=13 participants at risk Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period.	Placebo/Lumasiran n=13 participants at risk Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.	Lumasiran/Lumasiran n=26 participants at risk Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
Gastrointestinal disorders Abdominal pain	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	7.7% 1/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	3.8% 1/26 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.
Infections and infestations Post procedural infection	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	3.8% 1/26 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.
Infections and infestations Urinary tract infection	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	3.8% 1/26 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.
Infections and infestations Urosepsis	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	3.8% 1/26 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	3.8% 1/26 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Follicular lymphoma	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	3.8% 1/26 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.
Renal and urinary disorders Dysuria	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	7.7% 1/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	0.00% 0/26 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.
Renal and urinary disorders Renal impairment	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	0.00% 0/13 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.	3.8% 1/26 • DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60). Per the SAP, long-term safety of lumasiran (in the extension period \[EP\]) was to be summarized by treatment sequence (placebo/lumasiran \& lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. The lumasiran/lumasiran arm received lumasiran in both DB \& EP period hence, safety data is reported together for DB+EP period for this arm. Placebo/Lumasiran: first day of lumasiran dosing (Month 6) was considered baseline (Day 1) of EP.

Other adverse events

Additional Information

Chief Medical Officer

Alnylam Pharmaceuticals Inc

Phone: 866-330-0326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60