Trial Outcomes & Findings for A Study of Lumasiran in Infants and Young Children With Primary Hyperoxaluria Type 1 (NCT NCT03905694)

Last Updated: 2025-02-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

18 participants

Primary outcome timeframe

Baseline to Month 6

Results posted on

2025-02-14

Participant Flow

Participants took part in the study at investigative sites in France, Germany, Israel, the United Kingdom, and the United States from 22 April 2019 to 26 July 2024.

A total of 18 participants with Primary hyperoxaluria type 1 (PH1) were enrolled and treated in this study.

Participant milestones

Participant milestones
Measure	Lumasiran Participants weighing \<10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly (QM) for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month primary analysis period (PAP) \& QM during the 54-month extension period (EP). Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Primary Analysis Period STARTED	18
Primary Analysis Period COMPLETED	18
Primary Analysis Period NOT COMPLETED	0
Long-term Extension Period STARTED	18
Long-term Extension Period COMPLETED	18
Long-term Extension Period NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Lumasiran in Infants and Young Children With Primary Hyperoxaluria Type 1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Age, Continuous	43.7 months STANDARD_DEVIATION 21.30 • n=99 Participants
Sex: Female, Male Female	10 Participants n=99 Participants
Sex: Female, Male Male	8 Participants n=99 Participants
Race/Ethnicity, Customized White	16 Participants n=99 Participants
Race/Ethnicity, Customized Other	2 Participants n=99 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=99 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	16 Participants n=99 Participants
Spot Urinary Oxalate:Creatinine Ratio	0.6306 mmol/mmol STANDARD_DEVIATION 0.42636 • n=99 Participants

PRIMARY outcome

Timeframe: Baseline to Month 6

Population: Efficacy Analysis Set: All participants who received any amount of lumasiran and had at least 1 valid spot urinary oxalate:creatinine ratio value at baseline and at least 1 valid spot urinary oxalate:creatinine ratio value from assessment(s) at Month 3 through Month 6.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Percentage Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6	-71.97 percent change Standard Error 2.706

SECONDARY outcome

Timeframe: From Month 6 to Month 60

Population: Efficacy analysis set included all participants who were treated with Lumasiran and had at least one spot urinary oxalate:creatinine ratio value at baseline and at least one spot urinary oxalate:creatinine ratio value from assessment(s) at Month 6 through Month 60.

A negative change from baseline indicates a favorable outcome.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Percentage Change in Spot Urinary Oxalate: Creatinine Ratio in the Extension Period (Month 6 to End of Study [Month 60])	-74.48 percent change Standard Error 4.246

SECONDARY outcome

Timeframe: Up to 60 months

Percentage of time that spot urinary oxalate: creatinine (UOx:Cr) ratio level is at or below ≤ 1.5xULN is calculated as (cumulative months at or below near normalization threshold divided by cumulative months of assessments)\*100. Cumulative months in near-normalization is defined as the summation across all intervals that met the near-normal threshold and cumulative months of valid assessments is defined as the summation across all valid post-baseline collections. ULN levels of spot urinary oxalate to creatinine ratio where urine oxalate levels were analyzed using enzymatic assay. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Percentage of Time That Spot Urinary Oxalate: Creatinine Ratio is at or Below the Near-normalization Threshold (≤1.5 × Upper Limit of Normal (ULN) for Age)	68.95 percentage of time Interval 18.3 to 98.7

SECONDARY outcome

Timeframe: From Baseline to Month 6 and Month 60

The absolute change is represented as ratio of millimoles of urinary oxalate to millimoles of urinary creatinine.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Absolute Change in Spot Urinary Oxalate: Creatinine Ratio From Baseline Month 6	-0.4880 mmol/mmol Standard Error 0.09127
Absolute Change in Spot Urinary Oxalate: Creatinine Ratio From Baseline Month 60	-0.5179 mmol/mmol Standard Error 0.09929

SECONDARY outcome

Timeframe: Up to 60 months

The percentage of participants meeting the criteria (UOx:Cr ratio ≤ the ULN for age) at least at one post-baseline visit were reported for this outcome measure. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ the ULN for Age	100 percentage of participants

SECONDARY outcome

Timeframe: Up to 60 months

The percentage of participants meeting the criteria (UOx:Cr ratio ≤ 1.5xULN for age) at least at one post-baseline visit were reported for this outcome measure. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ 1.5xULN for Age	100 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Month 6 and Month 60

The lower limit of quantification (LLOQ) was 5.55 micromoles per liter (μmol/L). A negative change from baseline indicates a favorable outcome.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Percentage Change in Plasma Oxalate From Baseline to End of Study (Month 60) Month 6	-32.06 percent change Standard Error 6.711
Percentage Change in Plasma Oxalate From Baseline to End of Study (Month 60) Month 60	-24.78 percent change Standard Error 12.814

SECONDARY outcome

Timeframe: From Baseline to Month 6 and Month 60

The LLOQ was 5.55 μmol/L. A negative change from Baseline indicates a favorable outcome.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Absolute Change in Plasma Oxalate From Baseline to End of Study (Month 60) Month 6	-5.03 µmol/L Standard Error 1.294
Absolute Change in Plasma Oxalate From Baseline to End of Study (Month 60) Month 60	-5.03 µmol/L Standard Error 1.859

SECONDARY outcome

Timeframe: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24

Population: PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Number analyzed is the number of participants with data available for analysis at specified timepoints.

Cmax was the maximum plasma concentration post-dose within the pharmacokinetic (PK) sampling time frame. Higher Cmax generally indicates higher drug exposure.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Maximum Observed Plasma Concentration (Cmax) of Lumasiran Day 1	886 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 58.9
Maximum Observed Plasma Concentration (Cmax) of Lumasiran Month 6	869 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 84.0
Maximum Observed Plasma Concentration (Cmax) of Lumasiran Month 12	1180 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 83.5
Maximum Observed Plasma Concentration (Cmax) of Lumasiran Month 18	878 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 94.0
Maximum Observed Plasma Concentration (Cmax) of Lumasiran Month 24	790 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 91.9

SECONDARY outcome

Timeframe: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24

Tmax was estimated by calculating the time required to reach the maximum plasma concentration (Cmax) after the drug administration. Lower Tmax generally indicates faster drug absorption from the administration site.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran Day 1	3.74 hours (h) Interval 1.87 to 8.1
Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran Month 6	4 hours (h) Interval 1.75 to 10.1
Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran Month 12	4 hours (h) Interval 1.75 to 7.25
Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran Month 18	3.64 hours (h) Interval 1.98 to 10.0
Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran Month 24	3.73 hours (h) Interval 1.67 to 10.3

SECONDARY outcome

Timeframe: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24

Population: PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints.

Elimination half-life was estimated from the terminal phase of the plasma concentration-time profile post-dose. Shorter half-life generally indicates rapid drug elimination from the body.

Outcome measures

Outcome measures
Measure	Lumasiran n=13 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Elimination Half-life (t1/2beta) of Lumasiran Day 1	5.46 hours (h) Interval 1.42 to 10.3
Elimination Half-life (t1/2beta) of Lumasiran Month 6	5.96 hours (h) Interval 3.04 to 9.0
Elimination Half-life (t1/2beta) of Lumasiran Month 12	3.52 hours (h) Interval 1.56 to 6.64
Elimination Half-life (t1/2beta) of Lumasiran Month 18	3.74 hours (h) Interval 1.62 to 13.9
Elimination Half-life (t1/2beta) of Lumasiran Month 24	4.99 hours (h) Interval 2.69 to 10.8

SECONDARY outcome

Timeframe: 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24

Population: PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints.

AUC0-24 was the total drug exposure calculated as the area under the plasma concentration-time curve from the time of dosing (t = 0) to 24 hours.

Outcome measures

Outcome measures
Measure	Lumasiran n=14 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran Day 1	8050 hoursnanograms per milliliter (hng/mL) Geometric Coefficient of Variation 37.7
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran Month 6	8450 hoursnanograms per milliliter (hng/mL) Geometric Coefficient of Variation 41.1
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran Month 12	10800 hoursnanograms per milliliter (hng/mL) Geometric Coefficient of Variation 39.3
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran Month 18	8420 hoursnanograms per milliliter (hng/mL) Geometric Coefficient of Variation 57.2
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran Month 24	7420 hoursnanograms per milliliter (hng/mL) Geometric Coefficient of Variation 61.6

SECONDARY outcome

Timeframe: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24

AUC0-last was the total drug exposure calculated as the area under the plasma concentration-time curve from time 0 to the time of the last measurable (quantifiable) concentration (C\_last).

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran Day 1	7870 h*ng/mL Geometric Coefficient of Variation 33.4
Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran Month 6	6620 h*ng/mL Geometric Coefficient of Variation 95.5
Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran Month 12	8480 h*ng/mL Geometric Coefficient of Variation 76.1
Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran Month 18	5770 h*ng/mL Geometric Coefficient of Variation 155.0
Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran Month 24	7100 h*ng/mL Geometric Coefficient of Variation 80.0

SECONDARY outcome

Timeframe: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24

Population: PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints.

AUC0-infinity was the total drug exposure estimated as the area under the plasma concentration-time curve from time 0 extrapolated to infinity.

Outcome measures

Outcome measures
Measure	Lumasiran n=13 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran Month 18	11600 h*ng/mL Geometric Coefficient of Variation 48.6
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran Day 1	9180 h*ng/mL Geometric Coefficient of Variation 31.7
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran Month 6	8840 h*ng/mL Geometric Coefficient of Variation 40.9
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran Month 12	11900 h*ng/mL Geometric Coefficient of Variation 29.2
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran Month 24	9610 h*ng/mL Geometric Coefficient of Variation 48.8

SECONDARY outcome

Timeframe: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24

Population: PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints.

Apparent clearance was calculated by dividing the area under the plasma concentration-time curve from zero infinity by the dose administered. A higher clearance generally indicates faster elimination from the body.

Outcome measures

Outcome measures
Measure	Lumasiran n=13 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Apparent Clearance (CL/F) of Lumasiran Month 18	6.87 liters per hour (L/h) Geometric Coefficient of Variation 30.6
Apparent Clearance (CL/F) of Lumasiran Month 24	8.22 liters per hour (L/h) Geometric Coefficient of Variation 37.7
Apparent Clearance (CL/F) of Lumasiran Month 12	7.06 liters per hour (L/h) Geometric Coefficient of Variation 28.3
Apparent Clearance (CL/F) of Lumasiran Day 1	8.62 liters per hour (L/h) Geometric Coefficient of Variation 24.0
Apparent Clearance (CL/F) of Lumasiran Month 6	10.2 liters per hour (L/h) Geometric Coefficient of Variation 32.3

SECONDARY outcome

Timeframe: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24

Population: PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints.

Apparent Volume of Distribution generally indicates the extent of drug distribution in the body.

Outcome measures

Outcome measures
Measure	Lumasiran n=13 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Apparent Volume of Distribution (V/F) of Lumasiran Day 1	57.2 Liters (L) Geometric Coefficient of Variation 69.8
Apparent Volume of Distribution (V/F) of Lumasiran Month 12	36 Liters (L) Geometric Coefficient of Variation 75.6
Apparent Volume of Distribution (V/F) of Lumasiran Month 6	81 Liters (L) Geometric Coefficient of Variation 71.1
Apparent Volume of Distribution (V/F) of Lumasiran Month 18	43.1 Liters (L) Geometric Coefficient of Variation 107.1
Apparent Volume of Distribution (V/F) of Lumasiran Month 24	57.6 Liters (L) Geometric Coefficient of Variation 70.6

SECONDARY outcome

Timeframe: From Baseline to Month 6 and Month 60

eGFR \[in milliliters per minute per 1.73 meters square (mL/min/1.73m\^2)\] was calculated from serum creatinine (SCr) based on the Schwartz Bedside Formula for participants ≥12 months of age at the time of assessment.

Outcome measures

Outcome measures
Measure	Lumasiran n=16 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Month 6	-0.263 mL/min/1.73m^2 Standard Error 3.8461
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Month 60	-4.525 mL/min/1.73m^2 Standard Error 4.8873

SECONDARY outcome

Timeframe: Up to 60 months

Population: Safety analysis set included all participants who had received at least one dose of Lumasiran.

An Adverse Event (AE) is any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Lumasiran n=18 Participants Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Number of Participants With Adverse Events (AEs)	18 Participants

Adverse Events

Lumasiran

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lumasiran n=18 participants at risk Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Infections and infestations Viral infection	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Ear and labyrinth disorders Ear haemorrhage	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.

Other adverse events

Other adverse events
Measure	Lumasiran n=18 participants at risk Participants weighing \<10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP \& QM during the 54-month EP. Participants who transitioned from \<10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to \<20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 \& 6 in the 6-month PAP \& Q3M during the 54-month EP. Participants with weight increases to a new dosing category (\<10 kg to ≥10 kg or \<20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased.
Blood and lymphatic system disorders Eosinophilia	5.6% 1/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Blood and lymphatic system disorders Iron deficiency anaemia	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Blood and lymphatic system disorders Leukopenia	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Blood and lymphatic system disorders Microcytosis	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Congenital, familial and genetic disorders Factor XII deficiency	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Ear and labyrinth disorders Ear pain	22.2% 4/18 • Number of events 5 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Eye disorders Conjunctivitis allergic	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Eye disorders Myopia	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Abdominal pain	22.2% 4/18 • Number of events 4 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Anal pruritus	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Aphthous ulcer	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Constipation	16.7% 3/18 • Number of events 3 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Dental caries	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Diarrhoea	16.7% 3/18 • Number of events 4 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Mouth ulceration	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Nausea	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Teething	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Toothache	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Gastrointestinal disorders Vomiting	33.3% 6/18 • Number of events 13 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
General disorders Fatigue	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
General disorders Influenza like illness	11.1% 2/18 • Number of events 3 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
General disorders Injection site haematoma	5.6% 1/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
General disorders Injection site reaction	16.7% 3/18 • Number of events 4 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
General disorders Injection site urticaria	5.6% 1/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
General disorders Pyrexia	44.4% 8/18 • Number of events 16 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
General disorders Vessel puncture site haematoma	5.6% 1/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Asymptomatic bacteriuria	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Bronchitis	11.1% 2/18 • Number of events 3 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations COVID-19	16.7% 3/18 • Number of events 3 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Conjunctivitis	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Conjunctivitis bacterial	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Croup infectious	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Cystitis	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Ear infection	16.7% 3/18 • Number of events 4 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Eye infection	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Gastroenteritis	27.8% 5/18 • Number of events 5 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Gastroenteritis viral	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Influenza	22.2% 4/18 • Number of events 5 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Nasopharyngitis	22.2% 4/18 • Number of events 14 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Oral herpes	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Otitis media	11.1% 2/18 • Number of events 4 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Pharyngitis	16.7% 3/18 • Number of events 4 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Pharyngitis streptococcal	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Pneumonia	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Pneumonia bacterial	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Rhinitis	27.8% 5/18 • Number of events 10 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Streptococcal infection	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Tonsillitis	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Tooth infection	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Upper respiratory tract infection	27.8% 5/18 • Number of events 9 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Urinary tract infection	16.7% 3/18 • Number of events 3 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Varicella	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Viral infection	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Infections and infestations Viral pharyngitis	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Injury, poisoning and procedural complications Arthropod bite	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Injury, poisoning and procedural complications Arthropod sting	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Injury, poisoning and procedural complications Fall	5.6% 1/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Injury, poisoning and procedural complications Hand fracture	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Injury, poisoning and procedural complications Head injury	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Injury, poisoning and procedural complications Skin abrasion	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Injury, poisoning and procedural complications Ulna fracture	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Injury, poisoning and procedural complications Upper limb fracture	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Investigations Blood alkaline phosphatase increased	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Investigations Blood bicarbonate decreased	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Investigations Blood bilirubin increased	11.1% 2/18 • Number of events 3 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Investigations SARS-CoV-2 antibody test positive	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Investigations Transaminases increased	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Investigations Urine analysis abnormal	5.6% 1/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Investigations White blood cell count decreased	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Metabolism and nutrition disorders Hyperglycaemia	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Metabolism and nutrition disorders Hyperlipidaemia	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Metabolism and nutrition disorders Iron deficiency	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Metabolism and nutrition disorders Vitamin D deficiency	16.7% 3/18 • Number of events 3 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Musculoskeletal and connective tissue disorders Arthropathy	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Musculoskeletal and connective tissue disorders Muscle spasms	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Nervous system disorders Headache	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Psychiatric disorders Behaviour disorder	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Psychiatric disorders Bruxism	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Psychiatric disorders Irritability	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Psychiatric disorders Stress	5.6% 1/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Renal and urinary disorders Haematuria	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Renal and urinary disorders Proteinuria	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Renal and urinary disorders Renal impairment	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Reproductive system and breast disorders Gynaecomastia	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 3/18 • Number of events 7 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Respiratory, thoracic and mediastinal disorders Laryngeal obstruction	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	27.8% 5/18 • Number of events 8 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.6% 1/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Skin and subcutaneous tissue disorders Dermatitis contact	5.6% 1/18 • Number of events 3 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Skin and subcutaneous tissue disorders Eczema	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Skin and subcutaneous tissue disorders Excessive granulation tissue	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Skin and subcutaneous tissue disorders Pruritus	5.6% 1/18 • Number of events 1 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Skin and subcutaneous tissue disorders Rash	5.6% 1/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Skin and subcutaneous tissue disorders Rash maculo-papular	11.1% 2/18 • Number of events 2 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.
Investigations Blood creatinine increased	11.1% 2/18 • Number of events 3 • Up to 60 months Safety analysis set included all subjects who had received at least one dose of Lumasiran.

Additional Information

Chief Medical Officer

Alnylam Pharmaceuticals Inc.

Phone: 866-330-0326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee It is intended that after completion of the study, the data are to be submitted for publication in a scientific journal and/or for reporting at a scientific meeting. A separate publication by Institution or PI may not be submitted for publication until after this primary manuscript is published or following 12 months after completion of the study. A copy of any proposed publication based on this study, must be provided and confirmed received at the Sponsor at least 30 days before its submission.
Publication restrictions are in place

Restriction type: OTHER