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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020702 |
E.1.2 | Term | Hyperoxalemia |
E.1.2 | System Organ Class | 100000004861 |
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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 equation will be used to estimate GFR for children (age below 18), and CKD-EPI equation will be used for adults (age 18 or above). 4. Plasma oxalate concentration ≥10 μmol/L in total plasma oxalate. 5. Male or female subjects ≥ 2 years of age. 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 |
7. Inability to swallow size 4 capsules. 8. Subjects that have undergone transplantation (solid organ or bone marrow). 9. Subjects 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. (This includes 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. 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 total plasma oxalate concentration after 52 weeks of treatment. |
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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) |
Key secondary endpoint: 1. Change from baseline in kidney function (eGFR) after 52 weeks of treatment. 2. Frequency of kidney stones events after 52 weeks of treatment. Stone events are defined as (i) Patient- or investigator reported symptoms, or (ii) Stone passages or removals, or (iii) Increase in number of stones assessed by ultrasound. Other endpoints 3. Percent change from baseline in total plasma oxalate concentration after 52 weeks of treatment. 4. Subjects achieving ‘near-normalization’ of total plasma oxalate concentration (<10 µmol/L) at least twice during weeks 24 to 52 of treatment. 5. Change from baseline in myocardial function in the heart as measured by Speckle Tracking Echocardiography (STE) and traditional echocardiography. 6. Change from baseline in free plasma oxalate concentration after 52 weeks of treatment. 7. Change from baseline in urinary oxalate excretion after 52 weeks of treatment. 8. Change from baseline in grade of nephrocalcinosis as assessed by Ultrasound. 9. Change in number of O. formigenes in stool. 10. Association between change in number of O. formigenes in stool and change in total plasma oxalate concentration. 11. Change from baseline in score of Quality of Life questionnaire. 12. Change from baseline in markers for renal function, renal tubular capacity and inflammation: Urine: magnesium, phosphorus, citrate, calcium, glycolate, creatinine, urea, calcium oxalate crystals, pH, osmolality and urinary volume. Blood: magnesium, phosphorus, citrate, calcium, glycolate, BUN, ALP, bicarbonate, CRP, WBC, creatinine and cystatine C
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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. after 24 to 52 weeks of treatment 5. after 48 weeks of treatment 6. after 52 weeks of treatment 7. after 52 weeks of treatment 8. after 48 weeks of treatment 9. after 52 weeks of treatment 10. after 52 weeks of treatment 11. Quality of life will be taken once during baseline and this is compared to the results of week 8, 24, 40 and 52. 12. after 52 weeks 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 |
Tunisia |
United States |
Belgium |
France |
Germany |
Netherlands |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The trial ends when the last patient has completed the post-treatment safety follow-up period. The post-treatment safety follow-up period ends either two weeks after last dose date, or the day before the first dose date in the open-label extension study OC5-OL-02 (whichever occurs first).
Due to this post-treatment safety follow-up, the trial is anticipated to end approximately two weeks after LVLS. |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |