Evaluate the Effect of ALLN-177 in Reducing Urinary Oxalate in Patients With Hyperoxaluria and Kidney Stones

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and efficacy of different doses of ALLN 177 for reducing urinary oxalate excretion in patients with secondary hyperoxaluria and recurrent kidney stones.

Detailed Description
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This is a multicenter, randomized, double-blind, placebo controlled study to evaluate the efficacy of ALLN 177 compared with placebo in reducing the urinary excretion of oxalate in subjects with secondary hyperoxaluria and kidney stones. ALLN-177 is an orally administered form of oxalate decarboxylase. The goal of therapy with ALLN-177 is to reduce urinary oxalate excretion by decreasing the absorption of oxalate from the gastrointestinal tract. Eligible subjects will be randomized to 7 days of treatment with a dose ALLN-177 or placebo and following a washout period, crossed over to an alternate treatment. Urinary oxalate excretion will be assessed by 24-hr urine collections throughout the study. The study allows for up to 60 subjects.

Official Title
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A Phase 2b, Multi-center, Randomized, Double Blind, Placebo-controlled, Crossover Study to Evaluate Multiple Doses of ALLN-177 in Recurrent Calcium Oxalate Kidney Stone Formers With Hyperoxaluria

Conditions
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Secondary Hyperoxaluria, Nephrolithiasis, Kidney Stones, Hyperoxaluria, Dietary Hyperoxaluria

Intervention / Treatment
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* Drug: ALLN-177 low dose
* Drug: ALLN-177 mid dose
* Drug: ALLN-177 high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of enteric or idiopathic hyperoxaluria and at least one kidney stone within the past 2 years Hyperoxaluria at screening May be taking drugs for the prevention of stone disease Exclusion Criteria: Hyperuricosuria Glomerular filtration rate < 55 mL/min/1.73m2 Hypercalcemia or hypothyroidism Obstructive uropathy, chronic urosepsis, renal failure, renal tubular acidosis, primary hyperparathyroidism, primary hyperoxaluria, pure uric acid and cystine stones, and/or medullary sponge kidney Treatment with cholestyramine Average daily dietary intake of oxalate <75 mg per day

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo capsules (1, 2 or 5) PO TID | Drug: Placebo<br>* Placebo: 1, 2 or 5 capsules with meals PO 3 times per day<br>|
| Experimental: ALLN-177 low dose<br>ALLN-177 1,500 units/meal PO TID | Drug: ALLN-177 low dose<br>* ALLN-177 1,500 units (1 capsule)/meal PO 3 times per day<br>* Other names: Oxalate decarboxylase;|
| Experimental: ALLN-177 mid dose<br>ALLN-177 3,000 units/meal PO TID | Drug: ALLN-177 mid dose<br>* ALLN-177 3,000 units (2 capsules)/meal PO 3 times per day<br>* Other names: Oxalate decarboxylase;|
| Experimental: ALLN-177 high dose<br>ALLN-177 7,500 units/meal PO TID | Drug: ALLN-177 high dose<br>* ALLN-177 7,500 units (5 capsules)/meal PO 3 times per day<br>* Other names: Oxalate decarboxylase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean urinary oxalate excretion (mg/24 h) following treatment |  | on 7 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean urinary oxalate excretion (mg/24 h) |  | on 7 days of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Stones, Nephrolithiasis, Urine Oxalate, Hyperoxaluria, Enteric Hyperoxaluria, Idiopathic Hyperoxaluria, Urological Diseases, Kidney Diseases, Dietary Oxalate