Study of Lumasiran in Healthy Adults and Patients With Primary Hyperoxaluria Type 1

Alnylam Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Primary Hyperoxaluria Type 1 (PH1)

Treatments: Drug: Lumasiran; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02706886

2015-004407-23 (EudraCT Number)

ALN-GO1-001

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of lumasiran in healthy adult volunteers and subjects with primary hyperoxaluria type 1 (PH1). In Part A, single ascending dose (SAD) part, healthy adults were dosed with lumasiran or placebo once. In Part B, multiple ascending doses (MAD) part, patients with primary hyperoxaluria type 1 (PH1) were dosed with lumasiran or placebo. All patients that initially received placebo received lumasiran after completing placebo dosing.

Enrollment: 52 patients

Sex: All

Ages: 6 to 64 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for Parts A and B:

• Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception.
• Willing to provide written informed consent and to comply with study requirements.

Additional Inclusion Criteria for Part B:

• Confirmation of PH1 disease
• Meet 24 hour urine oxalate excretion requirements
• Estimated glomerular filtration rate (GFR) of >45 mL/min/1.73m^2
• If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days

Exclusion Criteria for Parts A and B:

• Clinically significant health concerns (with the exception of PH1 for patients in Part B)
• Clinically significant electrocardiogram (ECG) abnormalities
• Abnormal for aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and any other clinical safety laboratory result considered clinically significant
• Received an investigational agent within 3 months before the first dose of study drug or are in follow-up of another clinical study
• Known history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc)
• History of intolerance to subcutaneous injection

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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52 participants in 9 patient groups, including a placebo group

Part A: SAD: Placebo

Placebo Comparator group

Description:

A single dose of matching placebo will be administered subcutaneously (SC).

Treatment:

Drug: Placebo

Part A: SAD: Lumasiran 0.3 mg/kg

Experimental group

Description:

A single dose of 0.3 mg/kg lumasiran will be administered SC.

Treatment:

Drug: Lumasiran

Part A: SAD: Lumasiran 1.0 mg/kg

Experimental group

Description:

A single dose of 1.0 mg/kg lumasiran will be administered SC.

Treatment:

Drug: Lumasiran

Part A: SAD: Lumasiran 3.0 mg/kg

Experimental group

Description:

A single dose of 3.0 mg/kg lumasiran will be administered SC.

Treatment:

Drug: Lumasiran

Part A: SAD: Lumasiran 6.0 mg/kg

Experimental group

Description:

A single dose of 6.0 mg/kg lumasiran will be administered SC.

Treatment:

Drug: Lumasiran

Part B: MAD: Placebo

Placebo Comparator group

Description:

Participants with primary hyperoxaluria type 1 (PH1) will be treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo treated participants will cross over to their respective Part B lumasiran arms in the Part B: MAD Study Day 85-End of Study Period and will then be treated with lumasiran. The estimated total time on study was up to 546 days.

Treatment:

Drug: Placebo

Part B: MAD: Lumasiran 1.0 mg/kg qM

Experimental group

Description:

Participants with PH1 will be treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85.

Treatment:

Drug: Lumasiran

Part B: MAD: Lumasiran 3.0 mg/kg qM

Experimental group

Description:

Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85.

Treatment:

Drug: Lumasiran

Part B: MAD: Lumasiran 3.0 mg/kg q3M

Experimental group

Description:

Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85.

Treatment:

Drug: Lumasiran