Phase 2/3 Oxabact Study

Study Overview
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Brief Summary
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The purpose of this study is to determine if Oxalobacter formigenes is effective at lowering urinary oxalate levels in patients with primary hyperoxaluria.

Official Title
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A Phase 2/3, Double-blind, Randomized, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of OxabactTM to Reduce Urinary Oxalate in Subjects With Primary Hyperoxaluria.

Conditions
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Primary Hyperoxaluria

Intervention / Treatment
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* Biological: Oxalobacter formigenes
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent (as applicable for the age of the subject) Male or female subjects ≥ 2 years of age A mean urinary oxalate excretion of > 1.0 mmol/1.73m2/day from eligible urine collections performed during screening. A diagnosis of PH I or PH II by one of the following: Liver biopsy confirmation of deficient liver specific peroxisomal alanine-glyoxylate aminotransferase, (AGT) or mislocalization of AGT from peroxisomes to mitochondria (PH I) or deficient glyoxylate reductase/hydroxypyruvate reductase (GRHPR) activity (PH II) Homozygosity or compound heterozygosity for a known mutation in the causative genes for PH I and PH II. Increased glycolate excretion for PH I or increased L-glycerate excretion for PH II. Subjects receiving pyridoxine must be receiving a stable dose for at least 3 months prior to entry into the study and must remain on the stable dose during the study. Subjects not receiving pyridoxine at study entry must be willing to refrain from initiating pyridoxine during study participation. Renal function defined as an estimated GFR ≥ 40 ml/min normalized to 1.73m2 body surface area, or a creatinine clearance of ≥ 40 ml/min normalized to 1.73m2 body surface area. Exclusion Criteria: Inability to collect two complete 24-hour urine samples. Each urine collection will be evaluated for completeness based on the urine acceptance criteria outlined in section 11.1. Subjects diagnosed as PH I who are pyridoxine naïve. Subjects that have undergone transplantation (solid organ or bone marrow). The existence of secondary hyperoxaluria, e.g. chronic gastrointestinal diseases such as cystic fibrosis, chronic inflammatory bowel disease and short-bowel syndrome. Current systemic (oral, IM, IV) antibiotic use or received systemic antibiotics within 14 days of study enrolment. History of a recurrent infection requiring >2 courses of systemic antibiotics in the past 6 months, or chronic antimicrobial suppression. Subjects who require immune suppressive therapy (including prednisone > 10mg daily for more than 2 weeks). Current treatment with a separate ascorbic acid preparation. Ascorbic acid up to 250mg/day as a component of a multivitamin formulation is not excluded. Known hypersensitivity to esomeprazol (or any of the other ingredients of this medicine), or to any other proton pump inhibitor medicine. (Nexium contraindication) Concomitant treatment with atazanavir. (Nexium contraindication) Pregnancy. Women of child-bearing potential who are not using adequate contraceptive precautions. Sexually active females, unless surgically sterile or at least 2 years post-menopausal, must be using a highly effective contraception (including oral, transdermal, injectable, or implanted contraceptives, IUD, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 30 days prior to the first dose of OxabactTM and must agree to continue using such precautions during the clinical study. Presence of a medical condition that the Principal Investigator considers likely to make the subject susceptible to adverse effect of study treatment or unable to follow study procedures. Note: Subjects from correctional facilities or asylums and subjects who are mentally handicapped are not to be included in the study. Participation in any study of an investigational product, biologic, device, or other agent within 30 days prior to randomization or not willing to forego other forms of investigational treatment during this study.

Ages Eligible for Study
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Minimum Age: 2 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 |
| --- | --- |
| Experimental: Oxabact (tm)<br> | Biological: Oxalobacter formigenes<br>* NLT (not less than) 10^7 CFU oxalobacter formigenes twice daily for 24 weeks<br>* Other names: OC3;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 8 |  | 8 weeks | 
| Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 in subsets of subjects defined by baseline urinary oxalate level, above and below median at screening |  | 24 weeks | 
| Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 in subsets of subjects defined by concomitant vitamin B6 therapy and no vitamin B6 therapy, in PH type I |  | 24 weeks | 
| Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 in subsets of subjects defined by eGFR of ≥90 mL/min/1.73m2 and < 90 mL/min/1.73m2 |  | 24 weeks | 
| Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 in subsets of subjects defined by PH Type I and PH Type II |  | 24 weeks | 
| Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 in subsets of subjects defined by age below 18 and age 18 or above |  | 24 weeks | 
| Percentage of subjects who have ≥20% reduction from Baseline urinary oxalate at Week 24 |  | 24 weeks | 
| Percentage change in plasma oxalate levels |  | 24 weeks | 
| Frequency of Stone Events (i.e. nephrolithiasis or markers thereof) |  | 24 weeks | 
| Correlation between percentage change in plasma oxalate levels and percentage change in urinary oxalate levels, from Baseline to Week 24 |  | 24 weeks | 
| Adverse events (AEs), hematology, clinical chemistry, urinalysis. |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oxalate, hyperoxaluria, PH