Evaluating ALLN-177 for Reducing Urinary Oxalate Excretion in Calcium Oxalate Kidney Stone Formers With Hyperoxaluria

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of ALLN-177 to reduce urinary oxalate excretion in patients with recurring kidney stones and enteric or idiopathic hyperoxaluria.

Detailed Description
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A multi-center, open-label, single arm study to evaluate the safety and the effect of ALLN-177 to reduce urinary oxalate excretion in recurrent kidney stone formers with associated hyperoxaluria. The study design includes a screening period to confirm eligibility, followed by a 3-day baseline period, 4-day open label treatment period with ALLN-177 and 4-day follow up period.

Official Title
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A Phase 2 Multicenter, Open Label, Single Arm Study Evaluating the Effect of ALLN-177 to Reduce Urinary Oxalate Excretion in Recurrent Calcium Oxalate Kidney Stone Formers With Hyperoxaluria

Conditions
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Hyperoxaluria, Nephrolithiasis

Intervention / Treatment
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* Drug: ALLN-177


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide informed consent Able to comply with study procedures History of enteric or idiopathic hyperoxaluria and at least one calcium oxalate kidney stone Hyperoxaluria >36mg of oxalate/24-hr May be taking drugs for the prevention of stone disease as long as there have been no changes in these medications for at least 3 months Exclusion Criteria: Uric acid ≥1.5g/24-hr Estimated glomerular filtration rate of < 60 mL/min Positive results from drug urine screen Requires daily vitamin C (defined as >10 days of >300 mg/day) Diagnosis of 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. Auto-immune disorder requiring high dose steroids or other immunosuppressant drugs. Subjects who are pregnant. Women of childbearing potential must have a negative pregnancy test prior to enrollment and must practice approved methods of birth control during the trial History of cancer diagnosis except for within the past 5 years excluding dermal squamous and/or basal cell carcinoma or cervical carcinoma in situ. Taken investigational compound within 30 days prior to the first day of the study Treatment with cholestyramine Average daily dietary intake of <75 mg oxalate per day calculated from diet recalls
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALLN-177<br>Recurrent Calcium Oxalate Stone Formers with Hyperoxaluria Subjects with Enteric or Idiopathic hyperoxaluria Dosing: 5 capsules of ALLN-177 orally (p.o.) up to 3 times daily (TID) with meals for 4 consecutive days. | Drug: ALLN-177<br>* ALLN-177 is orally administered oxalate decarboxylase (OxDc). The goal of oral therapy with ALLN-177 is to enzymatically degrade both dietary oxalate and endogenously produced oxalate secreted in the gastrointestinal tract resulting in decreased absorption and reduced urinary oxalate excretion.<br>* Other names: Oxalate decarboxylase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Period to Treatment Period 24-hour Urinary Oxalate Excretion | Change from Baseline is defined as Baseline value (average of Days 2 and 3) minus ALLN-177 treatment value (mean of Days 5, 6, and 7). | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline Period to Treatment Period in 24-hour Urinary Oxalate Excretion | Percent Change from Baseline is defined as baseline value (average of Days 2 and 3) minus ALLN-177 treatment value (mean of Days 5, 6, and 7) divided by baseline value times 100% | 7 days | 

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