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

NCT02706886 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: ALN-GO1-0012015-004407-23
• Study Type: interventional
• Target: 52
• Locations: 5 countries
• Sites: 9

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)

Keywords

PH1; Primary Hyperoxaluria; RNAi therapeutic; siRNA; AGT

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs)

  An AE is any untoward medical occurrence in a clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

  Part A (SAD): Up to 405 days; Part B (MAD): Up to 546 days

Secondary Outcomes (16)

• Maximum Concentration (Cmax) of Lumasiran in Plasma

  Part A (SAD): Day 1: predose, 30 minutes (min), 1 hour (h), 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h

• Time to Cmax (Tmax) of Lumasiran in Plasma

  Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h

• Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma

  Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h

• Terminal Half-life (t1/2) of Lumasiran in Plasma

  Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h

• Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran

  Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h

Study Arms (9)

Part A: SAD: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Part A: SAD: Lumasiran 0.3 mg/kg

EXPERIMENTAL

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

Drug: Lumasiran

Part A: SAD: Lumasiran 1.0 mg/kg

EXPERIMENTAL

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

Drug: Lumasiran

Part A: SAD: Lumasiran 3.0 mg/kg

EXPERIMENTAL

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

Drug: Lumasiran

Part A: SAD: Lumasiran 6.0 mg/kg

EXPERIMENTAL

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

Drug: Lumasiran

Part B: MAD: Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Part B: MAD: Lumasiran 1.0 mg/kg qM

EXPERIMENTAL

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.

Drug: Lumasiran

Part B: MAD: Lumasiran 3.0 mg/kg qM

EXPERIMENTAL

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.

Drug: Lumasiran

Part B: MAD: Lumasiran 3.0 mg/kg q3M

EXPERIMENTAL

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.

Drug: Lumasiran

Interventions

Lumasiran 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).

Also known as: ALN-GO1

Part A: SAD: Lumasiran 0.3 mg/kg; Part A: SAD: Lumasiran 1.0 mg/kg; Part A: SAD: Lumasiran 3.0 mg/kg; Part A: SAD: Lumasiran 6.0 mg/kg; Part B: MAD: Lumasiran 1.0 mg/kg qM; Part B: MAD: Lumasiran 3.0 mg/kg q3M; Part B: MAD: Lumasiran 3.0 mg/kg qM

Placebo 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: Placebo; Part B: MAD: Placebo

Eligibility Criteria

• Age: 6 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (9)

Clinical Trial Site

Bordeaux, France

Location

Clinical Trial Site

Lyon, France

Location

Clinical Trial Site

Paris, France

Location

Clinical Trial Site

Bonn, Germany

Location

Clinical Trial Site

Haifa, Israel

Location

Clinical Trial Site

Jerusalem, Israel

Location

Clinical Trial Site

Amsterdam, Netherlands

Location

Clinical Trial Site

Birmingham, United Kingdom

Location

Clinical Trial Site

London, United Kingdom

Location

Related Publications (2)

• Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2025 Dec 12. doi: 10.1007/s40262-025-01606-0. Online ahead of print.

  PMID: 41388232 DERIVED

• 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.

  PMID: 33985991 DERIVED

MeSH Terms

Conditions

Primary hyperoxaluria type 1; Hyperoxaluria, Primary

Interventions

lumasiran

Condition Hierarchy (Ancestors)

Hyperoxaluria; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Alnylam Pharmaceuticals Inc

Clinicaltrials@alnylam.com

866-330-0326

Study Officials

• Tracy McGregor, MD, MSCI

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2016
• First Posted: March 11, 2016
• Study Start: March 8, 2016
• Primary Completion: January 23, 2019
• Study Completion: January 23, 2019
• Last Updated: January 30, 2020
• Results First Posted: January 30, 2020

Record last verified: 2020-01

Locations

FR (3); IL (2); GB (2); NL (1); DE (1)