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

Primary Purpose

Primary Hyperoxaluria

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Oxalobacter formigenes
Placebo
Sponsored by
OxThera
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Hyperoxaluria focused on measuring hyperoxaluria, PH, oxalate

Eligibility Criteria

5 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Mayo Clinic (Department of Pediatric Nephrology)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

I

II

Arm Description

Size 2 enteric coated capsule containg lyophilized Oxalobacter formigenes

Size 2 enteric coated capsule containg placebo

Outcomes

Primary Outcome Measures

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

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
Percentage change in urinary oxalate (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24
Percentage change in urinary oxalate (expressed as mmole/1.73m2/day and as molar oxalate to creatinine ratio) from Baseline to Week 12
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
Frequency of AEs and SAEs
Laborator safety data

Full Information

First Posted
March 12, 2008
Last Updated
May 7, 2013
Sponsor
OxThera
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1. Study Identification

Unique Protocol Identification Number
NCT00638703
Brief Title
Study to Evaluate the Efficacy and Safety of OxabactTM on Reduction of Urinary Oxalate in Primary Hyperoxaluria Patients
Acronym
PHOENIX
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
October 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OxThera

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Hyperoxaluria
Keywords
hyperoxaluria, PH, oxalate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
I
Arm Type
Experimental
Arm Description
Size 2 enteric coated capsule containg lyophilized Oxalobacter formigenes
Arm Title
II
Arm Type
Placebo Comparator
Arm Description
Size 2 enteric coated capsule containg placebo
Intervention Type
Biological
Intervention Name(s)
Oxalobacter formigenes
Other Intervention Name(s)
- Oxabact(tm), - OC3
Intervention Description
NLT (not less than) 10^7 CFU Oxalobacter formigenes twice daily for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo
Primary Outcome Measure Information:
Title
Reduction in urinary oxalate Percentage change in urinary oxalate (expressed as mmole/1.73m2 /day) from Baseline to Week 24
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
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
Title
Percentage change in urinary oxalate (expressed as molar oxalate to creatinine ratio) from Baseline to Week 24
Time Frame
24 weeks
Title
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
Title
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
Title
Frequency of AEs and SAEs
Time Frame
over 24 weeks
Title
Laborator safety data
Time Frame
12 and 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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). 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). 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dawn Milliner, M.D
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic (Department of Pediatric Nephrology)
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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

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