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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
OxThera
ClinicalTrials.gov Identifier:
NCT00638703
First received: March 12, 2008
Last updated: May 7, 2013
Last verified: June 2011
  Purpose

The main 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, International 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:
  • Reduction in urinary oxalate Percentage change in urinary oxalate (expressed as mmole/1.73m2 /day) from Baseline to Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Percentage change in urinary oxalate (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Percentage change in urinary oxalate (expressed as mmole/1.73m2/day and as molar oxalate to creatinine ratio) from Baseline to Week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  • Frequency of AEs and SAEs [ Time Frame: over 24 weeks ] [ Designated as safety issue: Yes ]
  • Laborator safety data [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 43
Study Start Date: October 2007
Study Completion Date: October 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I
Size 2 enteric coated capsule containg lyophilized Oxalobacter formigenes
Biological: Oxalobacter formigenes
NLT (not less than) 10^7 CFU Oxalobacter formigenes twice daily for 24 weeks
Other Names:
  • - Oxabact(tm)
  • - OC3
Placebo Comparator: II
Size 2 enteric coated capsule containg placebo
Drug: Placebo
placebo

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ≥ 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:

    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 (GR/HPR) 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 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.
  6. Renal function defined as an estimated GFR ≥ 50 ml/min normalized to 1.73m2 body surface area

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 who 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.
  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: NCT00638703

Locations
United States, Minnesota
Mayo Clinic (Department of Pediatric Nephrology)
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
OxThera
Investigators
Principal Investigator: Dawn Milliner, M.D Mayo Clinic
  More Information

No publications provided

Responsible Party: OxThera
ClinicalTrials.gov Identifier: NCT00638703     History of Changes
Other Study ID Numbers: OC3-DB-01, DB-01
Study First Received: March 12, 2008
Last Updated: May 7, 2013
Health Authority: European Union: European Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by OxThera:
hyperoxaluria
PH
oxalate

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

ClinicalTrials.gov processed this record on July 26, 2014