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

A Phase 2, Multicenter, Open-Label, Extension Study to Evaluate the Long-Term Administration of ALN-GO1 in Patients With Primary Hyperoxaluria Type 1

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

Study Overview

• Status: Completed
• Conditions: Primary Hyperoxaluria; PH1; RNAi Therapeutic; siRNA; AGT
• Intervention / Treatment: Drug: Lumasiran

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • Clinical Trial Site
  • Lyon, France
    • Clinical Trial Site
  • Paris, France
    • Clinical Trial Site
• Germany
  • Bonn, Germany
    • Clinical Trial Site
• Israel
  • Haifa, Israel
    • Clinical Trial Site
  • Jerusalem, Israel
    • Clinical Trial Site
• Netherlands
  • Amsterdam, Netherlands
    • Clinical Trial Site
• United Kingdom
  • Birmingham, United Kingdom
    • Clinical Trial Site
  • London, United Kingdom
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M; 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).	Drug: Lumasiran; Multiple doses of lumasiran by SC injection; Other Names: ALN-GO1
Experimental: Lumasiran (ALN-GO1): 3.0 mg/kg QM; 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.	Drug: Lumasiran; Multiple doses of lumasiran by SC injection; Other Names: ALN-GO1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least One Adverse Event (AE)	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.	Baseline (Day -1) up to 54 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 24-hour Urinary Oxalate Corrected for Body Surface Area (BSA) at 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.	Baseline (Day -1) up to 54 months
Change From Baseline in 24-hour Urinary Oxalate:Creatinine Ratio at 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.	Baseline (Day -1) up to 54 months
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at 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.	Baseline (Day -1) up to 54 months

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals
• Investigators: Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2018
• Primary Completion (Actual): February 7, 2023
• Study Completion (Actual): February 7, 2023

Study Registration Dates

• First Submitted: November 17, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (Actual): November 22, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Urologic Diseases; Kidney Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Metabolism, Inborn Errors; Hyperoxaluria; Hyperoxaluria, Primary
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Hyperoxaluria; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hyperoxaluria, Primary; Renal Agents; Lumasiran
• Other Study ID Numbers: ALN-GO1-002; 2016-003134-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU.

Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes