A Study to Evaluate the Efficacy and Safety of Oxabact in Patients With Primary Hyperoxaluria

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of OC5 in patients with PH.

Detailed Description
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To evaluate the efficacy of Oxabact following 52 weeks treatment in subjects with maintained kidney function, but below the lower limit of the normal range (estimated glomerular filtration rate [eGFR] < 90 ml/min/1.73 m2) and a total plasma oxalate (Pox) concentration ≥ 10 μmol/L. Parameters to be evaluated include the ability to stabilise/reduce Pox concentration, to stabilise/improve kidney function and to reduce oxalate deposits in primary hyperoxaluria (PH) subjects.

Official Title
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A Phase III Double-blind, Randomised Study to Evaluate the Long-term Efficacy and Safety of Oxabact in Patients With Primary Hyperoxaluria

Conditions
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Primary Hyperoxaluria

Intervention / Treatment
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* Biological: Oxabact OC5 - Oxalobacter formigenes HC-1
* Other: 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) A diagnosis of PH (as determined by standard diagnostic methods). eGFR < 90 ml/min/1.73 m2. The Schwartz formula will be used to estimate GFR for children (age below 18), and CKD-EPI formula will be used for adults (age 18 or above). Plasma oxalate concentration ≥10 μmol/L in total plasma oxalate. Male or female patients ≥ 2 years of age. Patients receiving vitamin B6 must be receiving a stable dose for at least 3 months prior to screening and must not change the dose during the study. Patients not receiving vitamin B6 at study entry must be willing to refrain from initiating pyridoxine during study participation. Exclusion Criteria: Inability to swallow size 4 capsules. Subjects that have undergone transplantation (solid organ or bone marrow). Patients requiring dialysis or at immediate risk for kidney failure or expected to be in need of dialysis during the study period. The existence of secondary hyperoxaluria, e.g. hyperoxaluria due to bariatric surgery or chronic gastrointestinal diseases such as cystic fibrosis, chronic inflammatory bowel disease and short-bowel syndrome. Use of antibiotics to which O. formigenes is sensitive. (This includes current antibiotic use, or antibiotics use within 14 days of initiating study medication). Current treatment with a separate ascorbic acid preparation. Pregnant women (or women who are planning to become pregnant) or lactating women. Women of childbearing potential who are not using adequate contraceptive precautions. Please see section 7.3 regarding requirements for contraception. Presence of a medical condition that the Investigator considers likely to make the subject susceptible to adverse effect of study treatment or unable to follow study procedures or any condition that is likely to interfere with the study drug mechanism of action (such as abnormal GI function). Participation in any interventional study of another investigational product, biologic, device, or other agent within 60 days prior to the first dose of OC5 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 OC5 capsules<br>Oxabact OC5 - Oxalobacter formigenes HC-1 | Biological: Oxabact OC5 - Oxalobacter formigenes HC-1<br>* Active study drug<br>|
| Placebo Comparator: Placebo capsules<br>Placebo | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Plasma Oxalate Concentration After 52 Weeks of Treatment | Change from baseline in total plasma oxalate concentration after 52 weeks of treatment in micromole/liter | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Kidney Function | Evaluation based on eGFR calculation using the 2009 creatinine-based Schwartz bedside equation (for children below 18 years of age) (Schwartz et al., 2009) and 2009 creatinine-based CKD-EPI equation for adults (Levey et al., 2009). Subjects who turn 18 during the study period were continuously evaluated using the Schwartz equation, ie the equation used at baseline was kept throughout the study. | 52 weeks | 
| Frequency of Kidney Stone Events | Number of kidney stone events for each patient | Through week 48 |