E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020703 |
E.1.2 | Term | Hyperoxaluria |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of Oxabact TM to reduce urinary oxalate levels from Baseline to Week 24 in subjects with Primary Hyperoxaluria (PH). |
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E.2.2 | Secondary objectives of the trial |
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 Ca-oxalate supersaturation •The safety of Oxabact TM administered for 24 weeks in subjects with PH
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Note: This is an exploratory sub-study at the German site only.
Title: Effect of administration of Oxalobacter formigenes on the stability and structure of fecal bacterial populations in humans
Date: 26 June 2007
Version: 001
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E.3 | Principal 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 greater than or equal to 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
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
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E.4 | Principal 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 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. 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percentage change in urinary oxalate (expressed as mmole/1.73m2 /day) from Baseline to Week 24 (Day 168). The primary efficacy analysis will compare the percentage changes in urinary oxalate in the Oxabact TM and Placebo groups using a two-sided, two sample t-test. This analysis will be carried out in the efficacy population, defined as all randomized subjects who receive at least one dose of study drug and who provide at least one post-baseline measurement of urinary oxalate.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life assessment |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |