Clinical trial NCT03905694: A Study of Lumasiran in Infants and Young Children With Primary Hyperoxaluria Type 1
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Hyperoxaluria
Primary Hyperoxaluria Type 1 (PH1)
Keywords: PH1
Primary Hyperoxaluria
Hyperoxaluria
RNAi Therapeutic
siRNA
AGT
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-04-05
Enrollment: 18
Sex: ALL
Minimum age (years): 0
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Percentage Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
timeFrame: Baseline to Month 6
Secondary outcomes:
measure: Percentage Change in Spot Urinary Oxalate: Creatinine Ratio in the Extension Period (Month 6 to End of Study [Month 60])
timeFrame: From Month 6 to Month 60
measure: 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)
timeFrame: Up to 60 months
measure: Absolute Change in Spot Urinary Oxalate: Creatinine Ratio From Baseline
timeFrame: From Baseline to Month 6 and Month 60
measure: Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ the ULN for Age
timeFrame: Up to 60 months
measure: Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ 1.5xULN for Age
timeFrame: Up to 60 months
measure: Percentage Change in Plasma Oxalate From Baseline to End of Study (Month 60)
timeFrame: From Baseline to Month 6 and Month 60
measure: Absolute Change in Plasma Oxalate From Baseline to End of Study (Month 60)
timeFrame: From Baseline to Month 6 and Month 60
measure: Maximum Observed Plasma Concentration (Cmax) of Lumasiran
timeFrame: 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
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran
timeFrame: 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
measure: Elimination Half-life (t1/2beta) of Lumasiran
timeFrame: 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
measure: Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran
timeFrame: 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
measure: Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran
timeFrame: 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
measure: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran
timeFrame: 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
measure: Apparent Clearance (CL/F) of Lumasiran
timeFrame: 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
measure: Apparent Volume of Distribution (V/F) of Lumasiran
timeFrame: 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
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: From Baseline to Month 6 and Month 60
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Lyon
country: France
facility: Clinical Trial Site
city: Paris
country: France
facility: Clinical Trial Site
city: Bonn
country: Germany
facility: Clinical Trial Site
city: Haifa
country: Israel
facility: Clinical Trial Site
city: Jerusalem
country: Israel
facility: Clinical Trial Site
city: Nahariya
country: Israel
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.