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

• ClinicalTrials.gov Identifier: NCT03116685
• Recruitment Status: Completed
• First Posted: April 17, 2017
• Results First Posted: December 9, 2021
• Last Update Posted: December 10, 2021
• Sponsor: OxThera
• Information provided by (Responsible Party): OxThera

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Primary Hyperoxaluria	Biological: Oxabact OC5 - Oxalobacter formigenes HC-1; Other: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Double-blind, Randomised Study to Evaluate the Long-term Efficacy and Safety of Oxabact in Patients With Primary Hyperoxaluria
• Actual Study Start Date: January 9, 2018
• Actual Primary Completion Date: April 15, 2021
• Actual Study Completion Date: April 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Oxabact OC5 capsules; Oxabact OC5 - Oxalobacter formigenes HC-1	Biological: Oxabact OC5 - Oxalobacter formigenes HC-1; Active study drug
Placebo Comparator: Placebo capsules; Placebo	Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Plasma Oxalate Concentration After 52 Weeks of Treatment [ Time Frame: 52 weeks ]
   Change from baseline in total plasma oxalate concentration after 52 weeks of treatment in micromole/liter

Secondary Outcome Measures :

1. Change From Baseline in Kidney Function [ Time Frame: 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.
2. Frequency of Kidney Stone Events [ Time Frame: Through week 48 ]
   Number of kidney stone events for each patient

Eligibility Criteria

• Ages Eligible for Study: 2 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Tennessee

Vanderbilt University Hospital

Nashville, Tennessee, United States, 37232

Belgium

Centre Hospitalier Universitaire de Liège

Liège, Belgium

France

Hôpital Robert Debré

Paris, France, 75019

Germany

Kindernierenzentrum Bonn

Bonn, Germany, 53127

Spain

Hospital Vall d' Hebron

Barcelona, Spain

Tunisia

Hédi Chaker University Hospital

Sfax, Tunisia, 3000

Sahloul University Hospital

Sousse, Tunisia, 4054

Charles Nicolle University Hospital

Tunis, Tunisia, 1008

United Kingdom

Royal Free Hospital

London, United Kingdom, NW3 2QG

Nottingham Children's Hospital

Nottingham, United Kingdom, NG7 2UH

Sponsors and Collaborators

OxThera

Investigators

• Principal Investigator: Gesa Schalk, MD; KindernierenZentrum, Bonn, Germany

  Study Documents (Full-Text)

Documents provided by OxThera:

Study Protocol  [PDF] January 8, 2021

Statistical Analysis Plan  [PDF] February 8, 2021

More Information

• Responsible Party: OxThera
• ClinicalTrials.gov Identifier: NCT03116685
• Other Study ID Numbers: OC5-DB-02
• First Posted: April 17, 2017
• Results First Posted: December 9, 2021
• Last Update Posted: December 10, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hyperoxaluria, Primary; Hyperoxaluria; Kidney Diseases; Urologic Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases