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

Phase 3

Completed

• Conditions: Primary Hyperoxaluria
• Interventions: Biological: Oxabact OC5 - Oxalobacter formigenes HC-1; Other: Placebo

• Registration Number: NCT03116685
• Lead Sponsor: OxThera

Brief Summary

This study will evaluate the efficacy and safety of OC5 in patients with PH.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2017-04-07
• Study First Submitted QC: 2017-04-14
• Study First Posted: 2017-04-17
• Study Start: 2018-01-09
• Primary Completion: 2021-04-15
• Study Completion: 2021-04-15
• Status Verified: 2021-10
• Results First Submitted: 2021-10-06
• Results First Submitted QC: 2021-11-11
• Results First Posted: 2021-12-09
• Last Update Submitted: 2021-12-09
• Last Update Posted: 2021-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. Signed informed consent (as applicable for the age of the subject)
2. A diagnosis of PH (as determined by standard diagnostic methods).
3. 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).
4. Plasma oxalate concentration ≥10 μmol/L in total plasma oxalate.
5. Male or female patients ≥ 2 years of age.
6. 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

1. Inability to swallow size 4 capsules.
2. Subjects that have undergone transplantation (solid organ or bone marrow).
3. Patients requiring dialysis or at immediate risk for kidney failure or expected to be in need of dialysis during the study period.
4. 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.
5. Use of antibiotics to which O. formigenes is sensitive. (This includes current antibiotic use, or antibiotics use within 14 days of initiating study medication).
6. Current treatment with a separate ascorbic acid preparation.
7. Pregnant women (or women who are planning to become pregnant) or lactating women.
8. Women of childbearing potential who are not using adequate contraceptive precautions. Please see section 7.3 regarding requirements for contraception.
9. 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).
10. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oxabact OC5 capsules	Oxabact OC5 - Oxalobacter formigenes HC-1	Oxabact OC5 - Oxalobacter formigenes HC-1
Placebo capsules	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Plasma Oxalate Concentration After 52 Weeks of Treatment	52 weeks	Change from baseline in total plasma oxalate concentration after 52 weeks of treatment in micromole/liter

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Kidney Function	52 weeks	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.
Frequency of Kidney Stone Events	Through week 48	Number of kidney stone events for each patient

Trial Locations

Locations (10)

Hédi Chaker University Hospital; 🇹🇳 Sfax, Tunisia

Centre Hospitalier Universitaire de Liège; 🇧🇪 Liège, Belgium

Sahloul University Hospital; 🇹🇳 Sousse, Tunisia

Nottingham Children's Hospital; 🇬🇧 Nottingham, United Kingdom

Royal Free Hospital; 🇬🇧 London, United Kingdom

Vanderbilt University Hospital; 🇺🇸 Nashville, Tennessee, United States

Charles Nicolle University Hospital; 🇹🇳 Tunis, Tunisia

Hôpital Robert Debré; 🇫🇷 Paris, France

Kindernierenzentrum Bonn; 🇩🇪 Bonn, Germany

Hospital Vall d' Hebron; 🇪🇸 Barcelona, Spain