Study to Evaluate the Efficacy and Safety of OxabactTM on Reduction of Urinary Oxalate in Primary Hyperoxaluria Patients

NCT00638703 | Completed Phase 2

• 2 other identifiers: OC3-DB-01DB-01
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to determine if Oxalobacter formigenes is effective at lowering urinary oxalate levels in patients with primary hyperoxaluria.

Conditions

Primary Hyperoxaluria

Keywords

hyperoxaluria; PH; oxalate

Outcome Measures

Primary Outcomes (1)

• Reduction in urinary oxalate Percentage change in urinary oxalate (expressed as mmole/1.73m2 /day) from Baseline to Week 24

  24 weeks

Secondary Outcomes (6)

• Percentage of subjects who are responders at Week 24 where response is defined as a 20% or greater reduction from Baseline urinary oxalate to Week 24

  24 weeks

• Percentage change in urinary oxalate (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24

  24 weeks

• Percentage change in urinary oxalate (expressed as mmole/1.73m2/day and as molar oxalate to creatinine ratio) from Baseline to Week 12

  12 weeks

• Percentage change in urinary oxalate (expressed as mmole/1.73m2/day and as molar oxalate to creatinine ratio) from Baseline to average of Weeks 12 and 24

  12 and 24 weeks

• Frequency of AEs and SAEs

  over 24 weeks

Study Arms (2)

I

EXPERIMENTAL

Size 2 enteric coated capsule containg lyophilized Oxalobacter formigenes

Biological: Oxalobacter formigenes

II

PLACEBO COMPARATOR

Size 2 enteric coated capsule containg placebo

Drug: Placebo

Interventions

Oxalobacter formigenes BIOLOGICAL

NLT (not less than) 10\^7 CFU Oxalobacter formigenes twice daily for 24 weeks

Also known as: - Oxabact(tm), - OC3

I

Placebo DRUG

placebo

II

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Male or female subjects ≥ 5 years of age
• Urinary oxalate excretion of \> 1.0 mmol/1.73m2/day at Baseline
• Documentation of diagnosis of PH I or PH II by any one of the following:
• 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)
• Homozygosity or compound heterozygosity for a known mutation in the causative genes for PH I and PH II
• Increased glycolate excretion for PH I or increased L-glycerate excretion for PH II
• 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: \<30% reduction of the urine oxalate levels) not receiving pyridoxine at study entry must be willing to refrain from initiating pyridoxine during study participation. Note: There will be no pyridoxine-naïve subjects enrolled in the study.
• Renal function defined as an estimated GFR ≥ 50 ml/min normalized to 1.73m2 body surface area

You may not qualify if:

• 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.
• Positive serum pregnancy test.
• 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.
• Subjects on hemodialysis or peritoneal dialysis.
• Subjects who have undergone transplantation (solid organ or bone marrow).
• Current systemic (oral, IM, IV) antibiotic use or received systemic antibiotics within 14 days of study enrolment.
• History of chronic, recurrent infections requiring \>2 courses of antibiotics in the past 6 months.
• History of malignancy except for basal or squamous cell skin cancer that has been excised.
• Unable to collect 24-hour urine samples or follow other study procedures.
• Subjects who cannot swallow a size 2 capsule.
• 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.
• Subjects who require immune suppressive therapy (including prednisone of \> 10mg daily for more than 2 weeks).
• Subjects from correctional facilities or asylums.
• Subjects who are mentally handicapped.

Sponsors & Collaborators

• OxThera: lead

Study Sites (1)

Mayo Clinic (Department of Pediatric Nephrology)

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Hyperoxaluria, Primary; Hyperoxaluria

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Dawn Milliner, M.D

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2008
• First Posted: March 19, 2008
• Study Start: October 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: October 1, 2008
• Last Updated: May 15, 2013

Record last verified: 2011-06

Locations

US (1)