An Extension Study of an Investigational Drug, Lumasiran (ALN-GO1), in Participants With Primary Hyperoxaluria Type 1

Phase 2

Completed

Conditions: PH1
AGT
Primary Hyperoxaluria
siRNA
RNAi Therapeutic

Interventions: Drug: Lumasiran

Registration Number: NCT03350451

Lead Sponsor: Alnylam Pharmaceuticals

Brief Summary: The purpose of this study is to evaluate the long-term safety and tolerability of lumasiran in participants with Primary Hyperoxaluria Type 1.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Enrollment within 12 months of completion of Study ALN-GO1-001
In the opinion of the investigator tolerated the study drug
If taking Vitamin B6 (pyridoxine), willing to remain on a stable regimen for the study duration
Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception
Willing to provide written informed consent and to comply with study requirements

Exclusion Criteria

Clinically significant health concerns (with the exception of PH1)
Clinically significant cardiovascular abnormality
Abnormal for AST/ALT and any other clinical safety laboratory result considered clinically significant
Requirement for chronic dialysis

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lumasiran (ALN-GO1): 3.0 mg/kg QM	Lumasiran	Participants enrolling from study 001B, received lumasiran, SC injection, at a starting dose of 3.0 mg/kg, QM, from Day 1 up to a maximum of Month 21. By Month 21, all participants were approved to change dosing regimen to receive lumasiran, SC injection, at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period.
Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M	Lumasiran	Participants enrolling from study 001B (NCT02706886), received lumasiran, subcutaneous (SC) injection, at a starting dose of 1.0 milligrams per kilograms (mg/kg) once monthly (QM) or 3.0 mg/kg once every 3 months \[Q3M\]) from Day 1 up to a maximum of Month 6. By Month 6, all participants were approved to change dose and/or dosing regimen to receive lumasiran, SC injection at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. All 3 participants who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6. As the cumulative dose administered over 6 months was the same for both 1 mg/kg QM \& 3 mg/kg Q3M, these participants were pooled into one arm as recommended by the Safety Review Committee (SRC).

Primary Outcome Measures

Name	Time	Method
Number of Participants With at Least One Adverse Event (AE)	Baseline (Day -1) up to 54 months	AE is any untoward medical occurrence in a participant or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Safety analysis set included all participants who received any amount of study drug.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in 24-hour Urinary Oxalate Corrected for Body Surface Area (BSA) at 54 Months	Baseline (Day -1) up to 54 months	Oxalate produced by the liver is the key toxic metabolite that drives disease pathology in participants with primary hyperoxaluria type 1 (PH1). The risk of disease complications increase continuously as oxalate levels increase. 24-hour urinary oxalate (millimole \[mmol\]/ 24 hour \[h\]/1.73 meters squared \[m\^2\]) corrected for BSA at each visit per participant was calculated as follows: \[Urine oxalate concentration (micromole per liter \[umol/L\])/1000 (umol/mmol)\]\\[24hour urine volume (mL)/1000 (mL/L)\]\ \[24 hours/actual collection hours\]\*1.73/(BSA). Baseline was the derived baseline value from the lumasiran treated period of Study ALN-GO1-001. A negative change from baseline indicated a favorable outcome. PD analysis set included all participants who received any amount of study drug and who had at least 1 post-dose urine sample for PD. Overall number of participants analyzed are the number of participants with data available for analysis.
Change From Baseline in 24-hour Urinary Oxalate:Creatinine Ratio at 54 Months	Baseline (Day -1) up to 54 months	Baseline is the derived baseline value from the lumasiran treated period of Study ALN-GO1-001. A negative change from baseline indicates a favorable outcome. PD analysis set included all participants who received any amount of study drug and who had at least 1 post-dose urine sample for PD.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at 54 Months	Baseline (Day -1) up to 54 months	Baseline was defined as the last measurement prior to the first dose of lumasiran in the ALN-GO1-001 study. eGFR was calculated based on the Modification of Diet in Renal Disease (MDRD) formula for participants \>=18 years of age at enrollment and the Schwartz Bedside formula for participants \<18 years of age at enrollment. eGFR based on MDRD formula was calculated as follows: eGFR (mL/min/1.73 m\^2) = 175 × (serum creatinine {SCr} \[μmol/deciliter(dL)\]/88.4)-1.154 × (age)-0.203 × (0.742, if female), or × (1.212, if African American) and based on Schwartz formula: eGFR (mL/min/1.73m2) = (36.2 × height \[cm\])/ SCr (μmol /dL). Safety analysis set included all participants who received any amount of study drug.