Establishing the Safety and Efficacy of Reloxaliase in Patients With Enteric Hyperoxaluria

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy, durability and long-term safety of reloxaliase in patients with enteric hyperoxaluria.

Detailed Description
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This is a phase 3, global, multi-center, randomized, double-blind, placebo-controlled study. This study is designed to determine the short- and long-term efficacy of reloxaliase in terms of reducing urinary oxalate excretion and clinical benefits compared to placebo.

Official Title
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Establishing the Safety and Efficacy of Reloxaliase (Oxalate Decarboxylase) in Patients With Enteric Hyperoxaluria: A Phase III Randomized, Double-Blind, Placebo-Controlled Study (URIROX-2)

Conditions
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Enteric Hyperoxaluria

Intervention / Treatment
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* Drug: Reloxaliase
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provided informed consent Age 18 years or older Has an underlying enteric disorder associated with malabsorption with known or suspected history of hyperoxaluria (e.g., history of kidney stones or oxalate nephropathy) Urinary oxalate ≥ 50 mg/24 hr Has at least 1 documented kidney stone within 2 years Exclusion Criteria: Acute renal failure or estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2 Has a known genetic, congenital, or other cause of kidney stones Unable or unwilling to discontinue Vitamin C supplementation >200mg daily Cannot establish baseline kidney stone burden

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reloxaliase<br>Reloxaliase (ALLN-177) 142 mg of oxalate decarboxylase (equivalent to 3,750 units of enzyme activity) per capsule | Drug: Reloxaliase<br>* Reloxaliase 2 capsules, orally, with each meal/snack, 3 to 5 times per day<br>* Other names: Oxalate decarboxylase;|
| Placebo Comparator: placebo<br>placebo capsule | Drug: Placebo<br>* Placebo 2 capsules, orally, with each meal/snack, 3 to 5 times per day<br>* Other names: Placebo capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in 24-hour urinary oxalate excretion during Weeks 1 to 4 | Efficacy will be assessed based on percent change from baseline to the average across Weeks 1 to 4, derived from all 24-hour collections during Weeks 1 to 4 on treatment | 4 weeks | 
| Proportion of subjects with kidney stone disease progression (composite of symptomatic kidney stone(s) or finding of new or enlarged kidney stone(s) on imaging) | Efficacy will be assessed by comparing kidney stone disease progression event rate on reloxaliase vs. placebo | up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in 24-hour urinary oxalate excretion during Weeks 16-24 | Efficacy will be assessed based on percent change from baseline to the average across Weeks 16-24, derived from all 24-hour collections during Weeks 16-24 on treatment | 24 weeks | 
| Proportion of subjects with a ≥ 20% reduction from baseline in 24-hour urinary oxalate excretion during Weeks 1-4 | Efficacy will be assessed based on proportion of subjects with ≥ 20% reduction from baseline to the average across Weeks 1-4, derived from all 24-hour collections during Weeks 1-4 on treatment | 4 weeks | 
| Hospitalizations or emergency room (ER) visits or procedures for the management of kidney stones | Efficacy will be assessed by comparing utilization on reloxaliase vs. placebo | up to 48 months | 
| Change in estimated glomerular filtration rate (eGFR) from baseline | Efficacy will be assessed by comparing the rate of change in eGFR on reloxaliase vs. placebo | up to 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney stone, hyperoxaluria, enteric hyperoxaluria, oxalate, kidney calcification