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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Hyperoxaluria
• Intervention / Treatment: Biological: Oxalobacter formigenes

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bonn, Germany, DE-53113
    • Universitätsklinikum Bonn, Department of Paediatric Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. 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.
3. A diagnosis of PH (as determined by standard diagnostic methods).
4. Patient should be on a stable dialysis regimen for at least two weeks before baseline.
5. Pre-dialysis plasma oxalate ≥40 micromole/L.

6. 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:

7. 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.
8. Ongoing treatment with immunosuppressive medication.
9. 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.
10. Use of antibiotics to which O. formigenes is sensitive, including current antibiotic use, or antibiotics use within 14 days of initiating study medication.
11. Current treatment with a separate ascorbic acid preparation. Standard of care vitamin supplement for patients on dialysis is allowed.
12. Pregnancy.
13. 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.
14. 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.
15. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxabact OC5 capsule; 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; 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.; Other Names: Oxabact; OC5

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: OxThera
• Collaborators: FP7-SME-2013 Research for the benefit of SMEs program
• Investigators: Principal Investigator: Gesa Schalk, M.D., University of Bonn

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2014
• Primary Completion (Actual): January 29, 2020
• Study Completion (Actual): January 29, 2020

Study Registration Dates

• First Submitted: November 20, 2013
• First Submitted That Met QC Criteria: November 26, 2013
• First Posted (Estimate): December 4, 2013

Study Record Updates

• Last Update Posted (Actual): January 10, 2022
• Last Update Submitted That Met QC Criteria: December 9, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: dialysis; hyperoxaluria; PH; oxalate
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Hyperoxaluria; Hyperoxaluria, Primary
• Other Study ID Numbers: OC5-OL-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No