Phase 2/3 Oxabact Study

NCT01037231 | Completed Phase 2 DMC

• 1 other identifier: OC3-DB-02
• Study Type: interventional
• Target: 36
• Locations: 3 countries
• Sites: 3

Brief Summary

The 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; oxalate; PH

Outcome Measures

Primary Outcomes (1)

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

  24 weeks

Secondary Outcomes (11)

• Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 8

  8 weeks

• Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 in subsets of subjects defined by baseline urinary oxalate level, above and below median at screening

  24 weeks

• Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 in subsets of subjects defined by concomitant vitamin B6 therapy and no vitamin B6 therapy, in PH type I

  24 weeks

• Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 in subsets of subjects defined by eGFR of ≥90 mL/min/1.73m2 and < 90 mL/min/1.73m2

  24 weeks

• Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 in subsets of subjects defined by PH Type I and PH Type II

  24 weeks

Study Arms (2)

Oxabact (tm)

EXPERIMENTAL

Biological: Oxalobacter formigenes

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Oxalobacter formigenes BIOLOGICAL

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

Also known as: Oxabact, OC3

Oxabact (tm)

Placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent (as applicable for the age of the subject)
• Male or female subjects ≥ 2 years of age
• A mean urinary oxalate excretion of \> 1.0 mmol/1.73m2/day from eligible urine collections performed during screening.
• A diagnosis of PH I or PH II by 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 (GRHPR) 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 into the study and must remain on the stable dose during the study. Subjects not receiving pyridoxine at study entry must be willing to refrain from initiating pyridoxine during study participation.
• Renal function defined as an estimated GFR ≥ 40 ml/min normalized to 1.73m2 body surface area, or a creatinine clearance of ≥ 40 ml/min normalized to 1.73m2 body surface area.

You may not qualify if:

• Inability to collect two complete 24-hour urine samples. Each urine collection will be evaluated for completeness based on the urine acceptance criteria outlined in section 11.1.
• Subjects diagnosed as PH I who are pyridoxine naïve.
• Subjects that have undergone transplantation (solid organ or bone marrow).
• The existence of secondary hyperoxaluria, e.g. chronic gastrointestinal diseases such as cystic fibrosis, chronic inflammatory bowel disease and short-bowel syndrome.
• Current systemic (oral, IM, IV) antibiotic use or received systemic antibiotics within 14 days of study enrolment.
• History of a recurrent infection requiring \>2 courses of systemic antibiotics in the past 6 months, or chronic antimicrobial suppression.
• Subjects who require immune suppressive therapy (including prednisone \> 10mg daily for more than 2 weeks).
• Current treatment with a separate ascorbic acid preparation. Ascorbic acid up to 250mg/day as a component of a multivitamin formulation is not excluded.
• Known hypersensitivity to esomeprazol (or any of the other ingredients of this medicine), or to any other proton pump inhibitor medicine. (Nexium contraindication)
• Concomitant treatment with atazanavir. (Nexium contraindication)
• Pregnancy.
• 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.
• 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. Note: Subjects from correctional facilities or asylums and subjects who are mentally handicapped are not to be included in the study.
• 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.

Sponsors & Collaborators

• OxThera: lead

Study Sites (3)

Mayo Clinic (Department of Pediatric Nephrology)

Rochester, Minnesota, 55905, United States

Location

University Children's Hospital (Division of Pediatric Nephrology)

Cologne, Germany

Location

Academy Medical Center, University of Amsterdam

Amsterdam, Netherlands

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: December 18, 2009
• First Posted: December 22, 2009
• Study Start: December 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: May 15, 2013

Record last verified: 2012-05

Locations

US (1); DE (1); NL (1)