primary hyperoxaluria MedDRA version: 9.1 Level: LLT Classification code 10020703 Term: Hyperoxaluria
Conditions
Interventions
Product Name: Oxabact(tm) - Oxalobacter formigenes, strain HC1
Product Code: OC3
Pharmaceutical Form: Capsule, hard
Current Sponsor code: OC3 drug subst
Sponsors
OxThera Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject (or legally acceptable representative) must give written informed consent (and assent for subjects = 12 years or country specific age as appropriate). For subjects less than 18 years of age, parent or guardian will provide informed consent and the subject will provide witnessed verbal assent 2. Male or female subjects greater than or equal to 5 years of age 3. Urinary oxalate excretion of > 1.0 mmol/1.73m2/day at Baseline 4. Documentation of diagnosis of PH I or PH II by any one of the following: a. Liver biopsy confirmation of deficient liver specific peroxisomal alanine-glyoxylate aminotransferase, (AGT) or mislocalization of AGT from peroxisomes to mitochondria (PH I) or deficient glyoxylate reductase/hydroxypyruvate reductase (GR/HPR) activity (PH II) b. Homozygosity or compound heterozygosity for a known mutation in the causative genes for PH I and PH II c. Increased glycolate excretion for PH I or increased L-glycerate excretion for PH II 5. Subjects receiving pyridoxine must be receiving a stable dose for at least 3 months prior to entry in to the study and must remain on the stable dose during the study. Other (non-pyridoxine naïve) subjects (e.g. Pyridoxine non-responder: =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnant, lactating, or actively menstruating women and women of child-bearing 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 OxabactTM and must agree to continue using such precautions during the clinical study. Note: A highly effective method of birth control is defined as one that results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomised partner. 2. Positive serum pregnancy test 3. Participation in any study of an investigational product, biologic, device, or other agent within 30 days prior to randomization or not willing to forego other forms of investigational treatment during this study 4. Subjects on hemodialysis or peritoneal dialysis 5. Subjects that have undergone transplantation (solid organ or bone marrow) 6. Chronic gastrointestinal disease associated with enteric hyperoxaluria, e.g., history of inflammatory bowel disease, colostomy. Note: For clarity, existence of Secondary Hyperoxaluria (e.g. with cystic fibrosis, chronic inflammatory bowel diseases, short bowel syndrome and/or deficiency of intestinal oxalate-degrading bacteria is included (as an exclusion criteria). 7. Current systemic (oral, IM, IV) antibiotic use or received systemic antibiotics within 14 days of study enrolment 8. History of chronic, recurrent infections requiring >2 courses of antibiotics in the past 6 months 9. History of malignancy except for basal or squamous cell skin cancer that has been excised 10. Unable to collect 24-hour urine samples or follow other study procedures 11. Subjects who cannot swallow a size 2 capsule 12. Presence of a medical condition that the Principal Investigator considers likely to make the subject susceptible to adverse effect of study treatment or unable to follow study procedures 13. Subjects who require immune suppressive therapy (including prednisone of > 10mg daily for more than 2 weeks). 14. Subjects from correctional facilities or asylums. 15. Subjects who are mentally handicapped.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of Oxabact TM to reduce urinary oxalate levels from Baseline to Week 24 in subjects with Primary Hyperoxaluria (PH).; Secondary Objective: To evaluate: •Percentage of subjects who have 20% or greater reduction from Baseline urinary oxalate at Week 24 •The effect of Oxabact TM on plasma oxalate levels •The effect of Oxabact TM on reduction of Ca-oxalate supersaturation •The safety of Oxabact TM administered for 24 weeks in subjects with PH ; Primary end point(s): The primary efficacy endpoint is the percentage change in urinary oxalate (expressed as mmole/1.73m2 /day) from Baseline to Week 24 (Day 168). The primary efficacy analysis will compare the percentage changes in urinary oxalate in the Oxabact TM and Placebo groups using a two-sided, two sample t-test. This analysis will be carried out in the efficacy population, defined as all randomized subjects who receive at least one dose of study drug and who provide at least one post-baseline measurement of urinary oxalate. | — |
Countries
France, Germany, Netherlands, United Kingdom
Outcome results
None listed