Primary Objective:To evaluate the efficacy of Oxabact TM to reduce urinary oxalate levels from Baseline to Week 24 in subjects with Primary Hyperoxaluria (PH).Secondary Objectives:To evaluate:* Percentage of subjects who have 20% or greater…
ID
Source
Brief title
Condition
- Inborn errors of metabolism
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Percentage change in urinary oxalate (expressed as mmole/1.73m2 /day) from
Baseline to Week 24 (Day 168).
Secondary outcome
* 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 (Day 168)
* Percentage change in urinary oxalate (expressed as mmole/1.73m2/day and as
molar oxalate to creatinine ratio) from Baseline to Week 12 (Day 84)
* 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
* Reduction of urinary calcium oxalate super saturation from Baseline to Week 24
* Reduction of urinary oxalate levels from Baseline to Week 24 in 2 subsets of
subjects defined by GFR of > 80 mL/min/1.73m2 (normal renal function) and < 80
mL/min/1.73m2 (mild to moderate reduction in renal function).
* Plasma oxalate levels at Weeks 12 and 24 and correlation with urinary oxalate
at these time points.
* Frequency of AEs and SAEs; laboratory safety data.
Background summary
Primary Hyperoxaluria is a metabolic disorder, characterized by excess
endogenous oxalate synthesis and excretion in the urine. Raised oxalate
excretion leads to calcifications in the kidneys. Primary Hyperoxaluria is an
inborn error of metabolism, and symptoms occur as early as the first month of
age. Calcification in the urinary tract can lead to decreased kidney function,
and 50% of patients need dialysis by 25 years. The use of OxabactTM is supposed
to lead to increased degradation of oxalate in the intestine. This generates a
suitable trans-epithelial gradient to promote the removal of endogenously
produced plasma oxalate by enteric elimination. Animal studies have shown that
enteric elimination of oxalate occurs both by the passive flow of oxalate
across the gut epithelia in response to a concentration gradient, as well as by
its active flux mediated by specific transporters. Enteric elimination is
expected to reduce the levels of urinary oxalate in both PH1 and PH2 patient
populations.
Study objective
Primary Objective:
To evaluate the efficacy of Oxabact TM to reduce urinary oxalate levels from
Baseline to Week 24 in subjects with Primary Hyperoxaluria (PH).
Secondary Objectives:
To evaluate:
* Percentage of subjects who have 20% or greater reduction from Baseline
urinary oxalate at Week 24
* The effect of Oxabact TM on plasma oxalate levels
* The effect of Oxabact TM on reduction of calcium-oxalate supersaturation
* The safety of Oxabact TM administered for 24 weeks in subjects with PH
Study design
This study is a double-blind, placebo-controlled, multi-center, international,
clinical study to evaluate the safety and efficacy of OxabactTM in the
reduction of urinary oxalate levels in subjects with PH. Eligible subjects
will be randomized (1:1) to receive either:
* NLT 10exp7 CFU of OxabactTM orally, twice daily with meals
* Placebo orally, twice daily with meals
Subjects will receive study drug for 24 weeks. Subjects who complete study
treatment will be eligible to participate in an extension study where all
subjects will receive open label OxabactTM.
Urinary oxalate will be measured at Baseline and at Weeks 4, 8, 12, 18, and
24. Plasma oxalate levels will be measured at Baseline and at Weeks 12 and
24. Laboratory safety assessments will be performed at Weeks 12 and 24.
All subjects in the randomized double-blind controlled study will be monitored
for safety throughout the study period
Intervention
One group receives during 24 weeks twice daily a capsule with Lyophilized O.
formigenes for oral administration. Strength: NLT 10exp7CFU/capsule
One group receives during 24 weeks twice daily a capsule withplacebo for oral
administration.
Randomisation is 1:1.
Study burden and risks
The treatment may harm the unborn child. Therefore, pregnancy is ruled out at
the start of the study. Male participants must be advise not to be enrolled in
the study if their partner wishes to become pregnant during the study time.
There may be side effects that are unknown at this time, such as stomach
problems, diarrhea, bloating, or flatus. Any stomach problems that are
currently present may worsen. The bacteria present in Oxabact* may cause
infection in blood. However, no such infections have been reported by the use
of Oxabact* to date.
Taking blood from the arm may cause discomfort and can leave a bruise. The
consequences related to the drawing of blood are usually considered to be of
minimal discomfort.
13709 Progress Boulevard
Alachua, Florida 32615
United States
13709 Progress Boulevard
Alachua, Florida 32615
United States
Listed location countries
Age
Inclusion criteria
1. The subject (or legally acceptable representative) must give written informed consent (and assent for subjects * 12 years). 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:
a. 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)
b. Homozygosity or compound heterozygosity for a known mutation in the causative genes for PH I and PH II
c. Increased glycolate excretion for PH I or increased L-glycerate excretion for PH II
d. Family history in a sibling with a definitive diagnosis of PH
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. 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 * 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 1 year post-menopausal, must be using a medically acceptable method of contraception (including oral, transdermal, injectable, or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, 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.
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 that have undergone transplantation (solid organ or bone marrow)
6. Chronic gastrointestinal disease associated with enteric hyperoxaluria, e.g., history of inflammatory bowel disease, colostomy
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).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-002328-14-NL |
| CCMO | NL18410.018.07 |