A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1

NCT03681184 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: ALN-GO1-0032018-001981-40
• Study Type: interventional
• Target: 39
• Locations: 8 countries
• Sites: 17

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of lumasiran in children and adults with primary hyperoxaluria type 1 (PH1).

Conditions

Primary Hyperoxaluria Type 1 (PH1)

Keywords

PH1; Primary hyperoxaluria; RNAi therapeutic; siRNA; AGT; Oxalate

Outcome Measures

Primary Outcomes (1)

• Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6

  Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.

  Baseline to Month 6

Secondary Outcomes (13)

• Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6

  Baseline to Month 6

• Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6

  Baseline to Month 6

• Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6

  Month 6

• Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6

  Month 6

• Percentage Change in Plasma Oxalate From Baseline to Month 6

  Baseline to Month 6

Other Outcomes (2)

• Rate of Renal Stone Events

  12-Month Period prior to Informed Consent, 6-Month DB Period

• Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound

  Baseline, Month 6

Study Arms (2)

Placebo/Lumasiran

PLACEBO COMPARATOR

Lumasiran-matching placebo (normal saline \[0.9% NaCl\]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period.

Drug: Placebo; Drug: Lumasiran

Lumasiran/Lumasiran

EXPERIMENTAL

Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.

Drug: Placebo; Drug: Lumasiran

Interventions

Placebo DRUG

Placebo by SC injection

Lumasiran/Lumasiran; Placebo/Lumasiran

Lumasiran DRUG

Lumasiran by SC injection

Also known as: ALN-GO1

Lumasiran/Lumasiran; Placebo/Lumasiran

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to provide written informed consent or assent and to comply with study requirements
• Confirmation of PH1 disease
• Meet the 24 hour urine oxalate excretion requirements
• 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) or clinical evidence of extrarenal systemic oxalosis
• Clinically significant abnormal laboratory results
• Known active or evidence of HIV or hepatitis B or C infection
• An estimated GFR of \< 30 mL/min/1.73m\^2 at screening
• Received an investigational agent within 30 days or 5 half-lives before the first dose of study drug or are in follow-up of another clinical study
• History of kidney or liver transplant
• Known history of multiple drug allergies or allergic reaction to an oligonucleotide or GalNAc
• History of intolerance to subcutaneous injection
• Women who are pregnant, planning a pregnancy, or breast-feeding or those of child bearing potential and not willing to use contraception
• History of alcohol abuse within the last 12 months, or unable or unwilling to limit alcohol consumption throughout the study

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (17)

Clinical Trial Site

San Diego, California, 92120, United States

Location

Clinical Trial Site

Jacksonville, Florida, 32216, United States

Location

Clinical Trial Site

Rochester, Minnesota, 55905, United States

Location

Clinical Trial Site

New York, New York, 10029, United States

Location

Clinical Trial Site

Cleveland, Ohio, 44195, United States

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

Nahariya, Israel

Location

Clinical Trial Site

Amsterdam, Netherlands

Location

Clinical Trial Site

Bern, Switzerland

Location

Clinical Trial Site

Dubai, United Arab Emirates

Location

Clinical Trial Site

Birmingham, United Kingdom

Location

Clinical Trial Site

London, NW3 2QG, United Kingdom

Location

Clinical Trial Site

London, WC1N 3JH, United Kingdom

Location

Related Publications (2)

• Frishberg Y, Saland JM, Lieske JC, Du W, Coenen M, Hogan J, Sellier-Leclerc AL, Groothoff JW, Kaspar C, Gansner JM, Hulton SA; ILLUMINATE-A study investigators. Final Results of the ILLUMINATE-A Phase 3 Clinical Trial of Lumasiran for Primary Hyperoxaluria 1. Clin J Am Soc Nephrol. 2025 Dec 4. doi: 10.2215/CJN.0000000916. Online ahead of print. No abstract available.

  PMID: 41343248 DERIVED

• Garrelfs SF, Frishberg Y, Hulton SA, Koren MJ, O'Riordan WD, Cochat P, Deschenes G, Shasha-Lavsky H, Saland JM, Van't Hoff WG, Fuster DG, Magen D, Moochhala SH, Schalk G, Simkova E, Groothoff JW, Sas DJ, Meliambro KA, Lu J, Sweetser MT, Garg PP, Vaishnaw AK, Gansner JM, McGregor TL, Lieske JC; ILLUMINATE-A Collaborators. Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1. N Engl J Med. 2021 Apr 1;384(13):1216-1226. doi: 10.1056/NEJMoa2021712.

  PMID: 33789010 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

• Medical Director

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: September 21, 2018
• Study Start: November 27, 2018
• Primary Completion: November 5, 2019
• Study Completion: January 12, 2024
• Last Updated: August 12, 2024
• Results First Posted: January 19, 2021

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); FR (2); NL (1); GB (3); CH (1); IL (3); DE (1); AE (1)