E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Hyperoxaluria (PH) |
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E.1.1.1 | Medical condition in easily understood language |
PH is a genetic disease associated with high levels of oxalate in the urine. Patients have kidney stones & calcium oxalate crystals. This damages the kidneys causing renal failure & premature death. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020703 |
E.1.2 | Term | Hyperoxaluria |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 OC5 to reduce urinary oxalate levels during 8 weeks in subjects with Primary Hyperoxaluria (PH). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of OC5 administered for 8 weeks in subjects with PH.
To evaluate the efficacy of OC5 to reduce plasma oxalate levels during 8 weeks in subjects with PH.
To evaluate changes in number of O. formigenes in faeces following administration of OC5. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Signed informed consent (as applicable for the age of the subject).
2.Male or female subjects ≥ 5 years of age.
3.A diagnosis of PH type I,II or III(as determined by standard diagnostic methods).
4.A mean urinary oxalate excretion of ≥ 1.0 mmol/24h/1.73m2 based on at least three eligible urine collections performed during baseline (weeks 1-4).
5.Renal function defined as an estimated GFR ≥ 40 ml/min normalised to 1.73m2 body surface area, or a creatinine clearance of ≥ 40 ml/min normalised to 1.73m2 body surface area.
6.Subjects receiving vitamin B6 must be receiving a stable dose for at least 3 months prior to screening and must not change the dose during the study. Subjects not receiving vitamin B6 at study entry must be willing to refrain from initiating pyridoxine during study participation. |
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E.4 | Principal exclusion criteria |
1.Inability to collect complete 24-hour urine samples. Each urine collection will be evaluated for completeness based on the urine qualitative criteria.
2.Inability to swallow size 4 capsules twice daily for 8 to 10 weeks.
3.Subjects that have undergone transplantation (solid organ or bone marrow).
4.The existence of secondary hyperoxaluria, e.g. hyperoxaluria due to bariatric surgery or chronic gastrointestinal diseases such as cystic fibrosis, chronic inflammatory bowel disease and short-bowel syndrome.
5.Use of antibiotics to which O. formigenes is sensitive, including chronic use, a history of more than two courses of antibiotic use during the past 6 months, current antibiotic use, or antibiotic use within 14 days of initiating study medication.
6.Subjects who require immune suppressive therapy.
7.Current treatment with a separate ascorbic acid preparation.
8.Pregnancy
9.Women of child-bearing potential who are not using adequate contraceptive precautions such as oral, transdermal, injectable, or implanted contraceptives, IUD, complete abstinence, use of a condom by the sexual partner, or sterile sexual partner.
10.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.
11.Participation in any study of an investigational product, biologic, device, or other agent within 30 days prior to screening or not willing to forego other forms of investigational treatment during this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in urinary oxalate levels from Baseline to week 8 of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline is the mean of urinary oxalate levels from week 1, 2, 3 and 4 of the study.
The week 8 of treatment measurement is the mean of the urinary oxalate level at week 12 and week 14 of the study (i.e. week 6 and week 8 of treatment). |
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E.5.2 | Secondary end point(s) |
1. Change in urinary oxalate levels from Baseline to week 8 of treatment in subsets of subjects defined by:
- baseline urinary oxalate level, above and below 1.5 mmol/24h/1.73m2.
- concomitant vitamin B6 therapy and no vitamin B6 therapy.
- eGFR of ≥90 mL/min/1.73m2 (normal renal function) and < 90 mL/min/ 1.73m2 (mild to moderate reduction in renal function).
- age below 18 and age 18 or above.
2. Number of subjects who reach urinary oxalate levels below 0.5, 0.7 and 1.0 mmol/24h/1.73m2 respectively from Baseline to week 8 of treatment.
3. Change in plasma oxalate levels from Baseline to week 8 of treatment.
4. Change in urinary oxalate from Baseline to week 4 of treatment.
5. Correlation between change in plasma oxalate levels and change in urinary oxalate levels from Baseline to week 8 of treatment.
6. Change in number of O.formigenes in faeces from Baseline to week 8 of treatment.
10. Safety:
– Adverse events (AE’s), haematology, clinical chemistry, urinalysis. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline is the mean of urinary oxalate levels from week 1, 2, 3 and 4 of the study.
The week 8 of treatment measurement is the mean of the urinary oxalate level at week 12 and week 14 of the study (i.e. week 6 and week 8 of treatment).
The week 4 of treatment measurement is the mean of the urinary oxalate levels at week 8 and 10 of the study (i.e. week 2 and week 4 of treatment). |
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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 | Yes |
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Study to investigate an improved Oxabact product (OC5) |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |