Study to Evaluate the Efficacy and Safety of Oxabact (OC5) in Primary Hyperoxaluria Patients Who Are on Dialysis

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 plasma oxalate levels in patients with primary hyperoxaluria who are on dialysis.

Official Title
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A Phase 2 Open-label Multi-centre Study to Evaluate the Efficacy and Safety of Oxabact® to Reduce Plasma Oxalate in Subjects With Primary Hyperoxaluria Who Are on Dialysis

Conditions
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Primary Hyperoxaluria

Intervention / Treatment
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* Biological: Oxalobacter formigenes


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). An appendix to the informed consent will be signed by patients continuing on treatment after week 14. Male or female subjects ≥ 2 years of age. Subjects have to be able to swallow size 4 capsules twice daily for 6 weeks, or use a gastric tube that allows for administration of size 4 capsules. A diagnosis of PH (as determined by standard diagnostic methods). Patient should be on a stable dialysis regimen for at least two weeks before baseline. Pre-dialysis plasma oxalate ≥40 micromole/L. Patients receiving vitamin B6 must be receiving a stable dose for at least 3 months prior to screening and must remain on the stable dose during the study. Patients not receiving vitamin B6 at study entry must be willing to refrain from initiating vitamin B6 during study participation. Exclusion Criteria: Inability to swallow size 4 capsules twice daily for 6 weeks or using a gastric tube not suited for administration of size 4 capsules via the tube. Ongoing treatment with immunosuppressive medication. 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, including current antibiotic use, or antibiotics use within 14 days of initiating study medication. Current treatment with a separate ascorbic acid preparation. Standard of care vitamin supplement for patients on dialysis is allowed. Pregnancy. Women of childbearing 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 OC5 and must agree to continue using such precautions during the clinical study. 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. Participation in any study of an investigational product, biologic, device, or other agent within 30 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxabact OC5 capsule<br>This is an open-label study so all patients will receive the active drug product, Oxalobacter formigenes, OC5. This will be administered as an enteric-coated capsules twice daily for 6 weeks of treatment. In Germany, the protocol has been amended such that patients can receive OC5 for a further 3 year of continued treatment after the initial part of the study. | Biological: Oxalobacter formigenes<br>* The dose will be (not less than) NLT ≥1E+09 colony forming units (CFU) twice daily. The dose (an enteric-coated capsule) will be administered orally with breakfast and dinner.<br>* Other names: OC5;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | Total plasma oxalate measured in umol/L | Baseline (average of week 2 & 4 pretreatment); treatment weeks 6, 8 & 10 (on treatment 2, 4, & 6 weeks); off treatment weeks 12 & 14 (2 & 4 weeks off treatment); patients were then eligible for treatment up to 3 years & oxalate was measured every 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Comparison of free plasma oxalate compared to the four week baseline period. | Baseline (average of week 2 & 4 pretreatment); treatment weeks 6, 8 & 10 (on treatment 2, 4, & 6 weeks); off treatment weeks 12 & 14 (2 & 4 weeks off treatment); patients were then eligible for treatment up to 3 years & oxalate was measured every 6 months | 
| Change in Left Ventricular Ejection Fraction From Baseline. | Mean left ventricular ejection fraction measured as a percentage. Reference range 55-70%. | At baseline and approximately every 6 months throughout the 3 year continued treatment. | 
| Speckle Tracking Echocardiography | Global longitudinal strain (GLS), which measures the maximal shortening of myocardial longitudinal length during systole compared to the resting length in diastole. The normal range for GLS is considered to be < -18%. | At baseline and approximately every 6 months throughout the 3 year continued treatment. | 

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