A Study of Lumasiran in Infants and Young Children With Primary Hyperoxaluria Type 1 (ILLUMINATE-B)

ILLUMINATE-B: An Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Lumasiran in Infants and Young Children With Primary Hyperoxaluria Type 1

The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of lumasiran in infants and young children with confirmed primary hyperoxaluria type 1 (PH1).

Study Overview

• Status: Completed
• Conditions: Primary Hyperoxaluria Type 1 (PH1); Primary Hyperoxaluria
• Intervention / Treatment: Drug: Lumasiran

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • 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
  • Nahariya, Israel
    • Clinical Trial Site
• United Kingdom
  • London, United Kingdom
    • Clinical Trial Site
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Clinical Trial Site
  • Texas
    • Houston, Texas, United States, 77030
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 5 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has genetic confirmation of primary hyperoxaluria type 1 (PH1)
• Meets urinary oxalate excretion requirements
• If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days

Exclusion Criteria:

• If <12 months old at screening, has an abnormally high serum creatinine
• If ≥12 months old at screening, has an estimated glomerular filtration rate (GFR) of ≤45 mL/min/1.73m^2
• Clinical evidence of systemic oxalosis
• History of kidney or liver transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lumasiran; Lumasiran will be administered by subcutaneous (SC) injection.	Drug: Lumasiran; Lumasiran will be administered by subcutaneous (SC) injection.; Other Names: ALN-GO1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6	Percent change in spot urinary oxalate:creatinine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.	Baseline to Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Spot Urinary Oxalate: Creatinine Ratio in the Extension Period (Month 6 to End of Study [Month 60])	A negative change from baseline indicates a favorable outcome.	From Month 6 to Month 60
Percentage of Time That Spot Urinary Oxalate: Creatinine Ratio is at or Below the Near-normalization Threshold (≤1.5 × Upper Limit of Normal (ULN) for Age)	Percentage of time that spot urinary oxalate: creatinine (UOx:Cr) ratio level is at or below ≤ 1.5xULN is calculated as (cumulative months at or below near normalization threshold divided by cumulative months of assessments)*100. Cumulative months in near-normalization is defined as the summation across all intervals that met the near-normal threshold and cumulative months of valid assessments is defined as the summation across all valid post-baseline collections. ULN levels of spot urinary oxalate to creatinine ratio where urine oxalate levels were analyzed using enzymatic assay. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073.	Up to 60 months
Absolute Change in Spot Urinary Oxalate: Creatinine Ratio From Baseline	The absolute change is represented as ratio of millimoles of urinary oxalate to millimoles of urinary creatinine.	From Baseline to Month 6 and Month 60
Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ the ULN for Age	The percentage of participants meeting the criteria (UOx:Cr ratio ≤ the ULN for age) at least at one post-baseline visit were reported for this outcome measure. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073.	Up to 60 months
Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ 1.5xULN for Age	The percentage of participants meeting the criteria (UOx:Cr ratio ≤ 1.5xULN for age) at least at one post-baseline visit were reported for this outcome measure. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073.	Up to 60 months
Percentage Change in Plasma Oxalate From Baseline to End of Study (Month 60)	The lower limit of quantification (LLOQ) was 5.55 micromoles per liter (μmol/L). A negative change from baseline indicates a favorable outcome.	From Baseline to Month 6 and Month 60
Absolute Change in Plasma Oxalate From Baseline to End of Study (Month 60)	The LLOQ was 5.55 μmol/L. A negative change from Baseline indicates a favorable outcome.	From Baseline to Month 6 and Month 60
Maximum Observed Plasma Concentration (Cmax) of Lumasiran	Cmax was the maximum plasma concentration post-dose within the pharmacokinetic (PK) sampling time frame. Higher Cmax generally indicates higher drug exposure.	2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran	Tmax was estimated by calculating the time required to reach the maximum plasma concentration (Cmax) after the drug administration. Lower Tmax generally indicates faster drug absorption from the administration site.	2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Elimination Half-life (t1/2beta) of Lumasiran	Elimination half-life was estimated from the terminal phase of the plasma concentration-time profile post-dose. Shorter half-life generally indicates rapid drug elimination from the body.	2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran	AUC0-24 was the total drug exposure calculated as the area under the plasma concentration-time curve from the time of dosing (t = 0) to 24 hours.	24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran	AUC0-last was the total drug exposure calculated as the area under the plasma concentration-time curve from time 0 to the time of the last measurable (quantifiable) concentration (C_last).	2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran	AUC0-infinity was the total drug exposure estimated as the area under the plasma concentration-time curve from time 0 extrapolated to infinity.	2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Apparent Clearance (CL/F) of Lumasiran	Apparent clearance was calculated by dividing the area under the plasma concentration-time curve from zero infinity by the dose administered. A higher clearance generally indicates faster elimination from the body.	2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Apparent Volume of Distribution (V/F) of Lumasiran	Apparent Volume of Distribution generally indicates the extent of drug distribution in the body.	2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)	eGFR [in milliliters per minute per 1.73 meters square (mL/min/1.73m^2)] was calculated from serum creatinine (SCr) based on the Schwartz Bedside Formula for participants ≥12 months of age at the time of assessment.	From Baseline to Month 6 and Month 60
Number of Participants With Adverse Events (AEs)	An Adverse Event (AE) is any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Up to 60 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Sas DJ, Magen D, Hayes W, Shasha-Lavsky H, Michael M, Schulte I, Sellier-Leclerc AL, Lu J, Seddighzadeh A, Habtemariam B, McGregor TL, Fujita KP, Frishberg Y; ILLUMINATE-B Workgroup. Phase 3 trial of lumasiran for primary hyperoxaluria type 1: A new RNAi therapeutic in infants and young children. Genet Med. 2022 Mar;24(3):654-662. doi: 10.1016/j.gim.2021.10.024. Epub 2021 Dec 8.
• Hayes W, Sas DJ, Magen D, Shasha-Lavsky H, Michael M, Sellier-Leclerc AL, Hogan J, Ngo T, Sweetser MT, Gansner JM, McGregor TL, Frishberg Y. Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 12-month analysis of the phase 3 ILLUMINATE-B trial. Pediatr Nephrol. 2023 Apr;38(4):1075-1086. doi: 10.1007/s00467-022-05684-1. Epub 2022 Aug 1.

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2019
• Primary Completion (Actual): June 29, 2020
• Study Completion (Actual): July 26, 2024

Study Registration Dates

• First Submitted: April 1, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (Actual): April 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 24, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: siRNA; PH1; Primary Hyperoxaluria; Hyperoxaluria; AGT; RNAi Therapeutic
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Hyperoxaluria; Hyperoxaluria, Primary; Renal Agents; Lumasiran
• Other Study ID Numbers: ALN-GO1-004; 2018-004014-17 (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 United States (US) and/or the European Union (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