Clinical trial NCT03681184: A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1
Official title: ILLUMINATE-A: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study With an Extended Dosing Period to Evaluate the Efficacy and Safety of Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Hyperoxaluria Type 1 (PH1)
Keywords: PH1
Primary hyperoxaluria
RNAi therapeutic
siRNA
AGT
Oxalate
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-09-21
Enrollment: 39
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
timeFrame: Baseline to Month 6
Secondary outcomes:
measure: Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6
timeFrame: Baseline to Month 6
measure: Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
timeFrame: Baseline to Month 6
measure: Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6
timeFrame: Month 6
measure: Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6
timeFrame: Month 6
measure: Percentage Change in Plasma Oxalate From Baseline to Month 6
timeFrame: Baseline to Month 6
measure: Absolute Change in Plasma Oxalate From Baseline to Month 6
timeFrame: Baseline to Month 6
measure: Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6
timeFrame: Baseline, Week 2, Months 1, 2, 3, 4, 5 and 6
measure: Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for BSA From Baseline in the Extension Period
timeFrame: From Baseline to Month 54 and Month 60
measure: Percentage Change in 24-hour Urinary Oxalate Excretion Corrected by BSA From Baseline in the Extension Period
timeFrame: From Baseline to Month 54 and Month 60
measure: Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During Lumasiran Treatment
timeFrame: Up to Month 60
measure: Absolute Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline in the Extension Period
timeFrame: From Baseline to Month 54 and Month 60
measure: Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline in the Extension Period
timeFrame: From Baseline to Month 54 and Month 60
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60).
Other outcomes:
measure: Rate of Renal Stone Events
timeFrame: 12-Month Period prior to Informed Consent, 6-Month DB Period
measure: Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound
timeFrame: Baseline, Month 6
Locations:
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: Jacksonville
country: United States
facility: Clinical Trial Site
state: Florida
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Cleveland
country: United States
facility: Clinical Trial Site
state: Ohio
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: Amsterdam
country: Netherlands
facility: Clinical Trial Site
city: Bern
country: Switzerland
facility: Clinical Trial Site
city: Dubai
country: United Arab Emirates
facility: Clinical Trial Site
city: Birmingham
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
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: 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.