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

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

Official Title
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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

Conditions
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Primary Hyperoxaluria Type 1 (PH1)

Intervention / Treatment
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* Drug: Placebo
* Drug: Lumasiran


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* Placebo by SC injection<br>Drug: Lumasiran<br>* Lumasiran by SC injection<br>* Other names: ALN-GO1;|
| Experimental: Lumasiran<br>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<br>* Placebo by SC injection<br>Drug: Lumasiran<br>* Lumasiran by SC injection<br>* Other names: ALN-GO1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6 | Absolute change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average absolute 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 | 
| Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6 | Percent change in 24-hour urinary oxalate:creatine 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 | 
| Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6 | The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA. | Month 6 | 
| Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6 | The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA. | Month 6 | 
| Percentage Change in Plasma Oxalate From Baseline to Month 6 | Percent change in plasma oxalate (umol/L) 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 | 
| Absolute Change in Plasma Oxalate From Baseline to Month 6 | Absolute change in plasma oxalate (umol/L) 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 | 
| Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6 | eGFR is calculated from serum creatinine based on the Modification of Diet in Renal Disease formula for patients ≥18 years of age and the Schwartz Bedside Formula for patients <18 years of age at screening. Change from baseline to Month 6 is reported. | Baseline, Week 2, Months 1, 2, 3, 4, 5 and 6 | 
| Absolute Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period |  | Up to 60 months | 
| Percentage Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period |  | Up to 60 months | 
| Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During the Extension Period |  | Up to 60 months | 
| Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline Over Time During the Extension Period |  | Up to 60 months | 
| Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time During the Extension Period |  | Up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PH1, Primary hyperoxaluria, RNAi therapeutic, siRNA, AGT, Oxalate