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 blood, the urine and throughout the body. The high oxalate levels damage the body in different ways (e.g. kidney stones) |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020702 |
E.1.2 | Term | Hyperoxalemia |
E.1.2 | System Organ Class | 100000019435 |
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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® following 52 weeks treatment in patients with maintained kidney function, but below the lower limit of the normal range (eGFR < 90 ml/min/1.73 m2) and a total plasma oxalate concentration ≥ 10 μmol/L at baseline
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E.2.2 | Secondary objectives of the trial |
To obtain additional safety data from 52 weeks continuous treatment with Oxabact®
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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. A diagnosis of PH (as determined by standard diagnostic methods). 3. eGFR < 90 ml/min/1.73 m2. The Schwartz formula will be used to estimate GFR for children (age below 18), and CKD-EPI formula will be used for adults (age 18 or above). 4. Plasma oxalate concentration ≥10 μmol/L in total plasma oxalate. 5. Male or female patients ≥ 2 years of age. 6. Patients 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. Patients 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 |
7. Inability to swallow size 4 capsules. 8. Subjects that have undergone transplantation (solid organ or bone marrow). 9. Patients requiring dialysis or at immediate risk for kidney failure or expected to be in need of dialysis during the study period. 10. 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. 11. Use of antibiotics to which O. formigenes is sensitive, including current antibiotic use, or antibiotics use within 14 days of initiating study medication. 12. Current treatment with a separate ascorbic acid preparation. 13. Pregnant women (or women who are planning to become pregnant) or lactating women. 14. Women of childbearing potential who are not using adequate contraceptive precautions. Please see section 7.3 regarding requirements for contraception. 15. Presence of a medical condition that the Investigator considers likely to make the subject susceptible to adverse effect of study treatment or unable to follow study procedures or any condition that is likely to interfere with the study drug mechanism of action (such as abnormal GI function). 16. Participation in any interventional study of another investigational product, biologic, device, or other agent within 60 days prior to the first dose of OC5 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 from baseline in plasma oxalate concentration after 52 weeks of treatment (total plasma oxalate concentration). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 52 weeks of treatment |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in plasma oxalate concentration (total plasma oxalate concentration)after 52 weeks of treatment in different subgroups of patients: • Patients with a baseline urinary oxalate excretion above and below 1.87 mmol/L/24h/1.73 m2 respectively (mean of the two first values during screening/baseline). • Patients above and below 18 years of age. • Patients with a baseline eGFR above and below 60 ml/min/1.73m2 respectively (mean of the obtained values during screening/baseline calculated by the Schwartz/CKD-EPI equation). 2. Change from baseline in kidney function (eGFR) after 52 weeks of treatment. 3. Change from baseline in kidney function (eGFR) after 52 weeks of treatment in different subgroups of patients: • Patients with a baseline urinary oxalate excretion above and below 1.87 mmol/L/24h/1.73 m2 respectively (mean of the two values during screening/baseline). • Patients above and below 18 years of age. • Patients with a baseline eGFR above and below 60 ml/min/1.73m2 respectively (mean of the obtained values during screening/baseline calculated by the Schwartz/CKD-EPI equation). 4. Change from baseline in myocardial function in the heart as measured by Speckle Tracking Echocardiography (STE). 5. Change from baseline in score of Quality of Life questionnaire. 6. Change from baseline in free plasma oxalate concentration after 52 weeks of treatment. 7. Change from baseline in free plasma oxalate concentration after 52 weeks of treatment in different subgroups of patients: • Patients with a baseline urinary oxalate excretion above and below 1.87 mmol/L/24h/1.73 m2 respectively (mean of the two first values during screening/baseline). • Patients above and below 18 years of age. • Patients with a baseline eGFR above and below 60 ml/min/1.73m2 respectively (mean of the obtained values during screening/baseline calculated by the Schwartz/CKD-EPI equation. Safety: Adverse events (AEs), vital signs, physical examination, hematology, clinical chemistry, urinalysis.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. after 52 weeks of treatment 2. after 52 weeks of treatment 3. after 52 weeks of treatment 4. STEs are measured twice during the baseline period and the mean is compared to the results after 24 and 48 weeks of treatment. 5. Questionnaires are taken twice during baseline and and the mean is compared to the results of Day 0 and week 8, 18, 24, 32, 40, 48 and 52.
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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) | 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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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 |
France |
Germany |
Netherlands |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |