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 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 two years continued treatment in subjects who have completed the Oxabact® OC5-DB-02 (ePHex) study. |
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E.2.2 | Secondary objectives of the trial |
To obtain additional safety data from two years continued 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. Participation in and completion of the ePHex study. 3. Subjects who had received vitamin B6 during ePHex should maintain a stable dose. Subjects not receiving vitamin B6 during ePHex must be willing to refrain from initiating pyridoxine during study participation. |
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E.4 | Principal exclusion criteria |
4. Inability to swallow size 4 capsules. 5. Use of antibiotics to which O.formigenes is sensitive. 6. Current treatment with a separate ascorbic acid preparation. 7. Pregnant women (or women who are planning to become pregnant) and lactating women. 8. Women of childbearing potential who are not using adequate contraceptive precautions. 9. 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). 10. Participation in any interventional study of another investigational product, biologic, device, or other agent 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 kidney function (eGFR) after 12 and 24 months of open- label Oxabact® treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 12 and 24 months of open-label Oxabact® treatment |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in total plasma oxalate concentration. 2. Frequency of kidney stones events. Stone events are defined as: (i) Subject- or investigator-reported symptoms, or (ii) Stone passages or removals, or (iii) Increase in the number of kidney stones as assessed by ultrasound. Other endpoints: 3. Change from baseline in myocardial function as measured by Speckle Tracking and traditional echocardiography. 4. Change from baseline in free plasma oxalate concentration. 5. Change from baseline in urinary oxalate. 6. Change from baseline in grade of nephrocalcinosis as assessed by ultrasound. 7. Change in number of O. formigenes in stool. 8. Association between change in number of O. formigenes in stool and change in total plasma oxalate concentration. 9. Change from baseline in score of Quality of Life questionnaire. 10. 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, 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 |
after 12 and 24 months of open-label Oxabact® 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 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 |
Belgium |
Germany |
Spain |
Tunisia |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 15 |