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

NCT ID: NCT02706886

Last Updated: 2020-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-08
• Study Completion Date: 2019-01-23

Brief Summary

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.

Conditions

Primary Hyperoxaluria Type 1 (PH1)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Part A: SAD: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo (sterile saline: 0.9% sodium chloride \[NaCl\]) will be administered SC once in Part A. In Part B matching placebo will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Part A: SAD: Lumasiran 0.3 mg/kg

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

Group Type: EXPERIMENTAL

Lumasiran

Intervention Type: DRUG

Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Part A: SAD: Lumasiran 1.0 mg/kg

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

Group Type: EXPERIMENTAL

Lumasiran

Intervention Type: DRUG

Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Part A: SAD: Lumasiran 3.0 mg/kg

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

Group Type: EXPERIMENTAL

Lumasiran

Intervention Type: DRUG

Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Part A: SAD: Lumasiran 6.0 mg/kg

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

Group Type: EXPERIMENTAL

Lumasiran

Intervention Type: DRUG

Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Part B: MAD: Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo (sterile saline: 0.9% sodium chloride \[NaCl\]) will be administered SC once in Part A. In Part B matching placebo will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Part B: MAD: Lumasiran 1.0 mg/kg qM

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.

Group Type: EXPERIMENTAL

Lumasiran

Intervention Type: DRUG

Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Part B: MAD: Lumasiran 3.0 mg/kg qM

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.

Group Type: EXPERIMENTAL

Lumasiran

Intervention Type: DRUG

Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Part B: MAD: Lumasiran 3.0 mg/kg q3M

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.

Group Type: EXPERIMENTAL

Lumasiran

Intervention Type: DRUG

Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Interventions

Lumasiran

Lumasiran will be administered SC once in Part A. In Part B lumasiran will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Intervention Type: DRUG

Placebo

Matching placebo (sterile saline: 0.9% sodium chloride \[NaCl\]) will be administered SC once in Part A. In Part B matching placebo will be administered SC qM (Days 1, 29 and 57) or q3M (Days 1 and 85).

Intervention Type: DRUG

Other Intervention Names

ALN-GO1

Eligibility Criteria

Inclusion Criteria

• 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.

• 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

• 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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alnylam Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tracy McGregor, MD, MSCI

Role: STUDY_DIRECTOR

Alnylam Pharmaceuticals

Locations

Clinical Trial Site

Bordeaux, , France

Clinical Trial Site

Lyon, , France

Clinical Trial Site

Paris, , France

Clinical Trial Site

Bonn, , Germany

Clinical Trial Site

Haifa, , Israel

Clinical Trial Site

Jerusalem, , Israel

Clinical Trial Site

Amsterdam, , Netherlands

Clinical Trial Site

Birmingham, , United Kingdom

Clinical Trial Site

London, , United Kingdom

Countries

France; Germany; Israel; Netherlands; United Kingdom

References

Frishberg Y, Deschenes G, Groothoff JW, Hulton SA, Magen D, Harambat J, Van't Hoff WG, Lorch U, Milliner DS, Lieske JC, Haslett P, Garg PP, Vaishnaw AK, Talamudupula S, Lu J, Habtemariam BA, Erbe DV, McGregor TL, Cochat P; study collaborators. Phase 1/2 Study of Lumasiran for Treatment of Primary Hyperoxaluria Type 1: A Placebo-Controlled Randomized Clinical Trial. Clin J Am Soc Nephrol. 2021 Jul;16(7):1025-1036. doi: 10.2215/CJN.14730920. Epub 2021 May 13.

Reference Type: DERIVED

PMID: 33985991 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2015-004407-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALN-GO1-001

Identifier Type: -

Identifier Source: org_study_id