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Phase 2/3 Oxabact Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
OxThera
ClinicalTrials.gov Identifier:
NCT01037231
First received: December 18, 2009
Last updated: May 7, 2013
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
Primary Hyperoxaluria
Biological: Oxalobacter formigenes
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2/3, Double-blind, Randomized, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of OxabactTM to Reduce Urinary Oxalate in Subjects With Primary Hyperoxaluria.

Resource links provided by NLM:


Further study details as provided by OxThera:

Primary Outcome Measures:
  • Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 8 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 in subsets of subjects defined by age below 18 and age 18 or above [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Percentage of subjects who have ≥20% reduction from Baseline urinary oxalate at Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Percentage change in plasma oxalate levels [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Frequency of Stone Events (i.e. nephrolithiasis or markers thereof) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Correlation between percentage change in plasma oxalate levels and percentage change in urinary oxalate levels, from Baseline to Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Adverse events (AEs), hematology, clinical chemistry, urinalysis. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: December 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oxabact (tm) Biological: Oxalobacter formigenes
NLT (not less than) 10^7 CFU oxalobacter formigenes twice daily for 24 weeks
Other Names:
  • Oxabact
  • OC3
Placebo Comparator: Placebo Drug: Placebo
placebo

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent (as applicable for the age of the subject)
  2. Male or female subjects ≥ 2 years of age
  3. A mean urinary oxalate excretion of > 1.0 mmol/1.73m2/day from eligible urine collections performed during screening.
  4. A diagnosis of PH I or PH II by one of the following:

    1. 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)
    2. Homozygosity or compound heterozygosity for a known mutation in the causative genes for PH I and PH II.
    3. 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 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.
  6. 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.

    Exclusion Criteria:

  7. 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.
  8. Subjects diagnosed as PH I who are pyridoxine naïve.
  9. Subjects that have undergone transplantation (solid organ or bone marrow).
  10. The existence of secondary hyperoxaluria, e.g. chronic gastrointestinal diseases such as cystic fibrosis, chronic inflammatory bowel disease and short-bowel syndrome.
  11. Current systemic (oral, IM, IV) antibiotic use or received systemic antibiotics within 14 days of study enrolment.
  12. History of a recurrent infection requiring >2 courses of systemic antibiotics in the past 6 months, or chronic antimicrobial suppression.
  13. Subjects who require immune suppressive therapy (including prednisone > 10mg daily for more than 2 weeks).
  14. Current treatment with a separate ascorbic acid preparation. Ascorbic acid up to 250mg/day as a component of a multivitamin formulation is not excluded.
  15. Known hypersensitivity to esomeprazol (or any of the other ingredients of this medicine), or to any other proton pump inhibitor medicine. (Nexium contraindication)
  16. Concomitant treatment with atazanavir. (Nexium contraindication)
  17. Pregnancy.
  18. 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.
  19. 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.
  20. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01037231

Locations
United States, Minnesota
Mayo Clinic (Department of Pediatric Nephrology)
Rochester, Minnesota, United States, 55905
Germany
University Children's Hospital (Division of Pediatric Nephrology)
Cologne, Germany
Netherlands
Academy Medical Center, University of Amsterdam
Amsterdam, Netherlands
Sponsors and Collaborators
OxThera
Investigators
Principal Investigator: Dawn Milliner, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: OxThera
ClinicalTrials.gov Identifier: NCT01037231     History of Changes
Other Study ID Numbers: OC3-DB-02
Study First Received: December 18, 2009
Last Updated: May 7, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by OxThera:
hyperoxaluria
oxalate
PH

Additional relevant MeSH terms:
Hyperoxaluria, Primary
Carbohydrate Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperoxaluria
Kidney Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Urologic Diseases

ClinicalTrials.gov processed this record on November 27, 2014