E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alport Syndrome (AS) and Primary Steroid-Resistent Focal Segmental Glomerulosclerosis (FSGS) |
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E.1.1.1 | Medical condition in easily understood language |
Alport syndrome (AS) and Focal Segmental Glomerulosclerosis (FSGS). AS and FSGS are both a type of kidney disease. |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001843 |
E.1.2 | Term | Alport's syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067757 |
E.1.2 | Term | Focal segmental glomerulosclerosis |
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 |
Primary Objectives: For all patients: • To evaluate the tolerability and safety of R3R01 administered orally for 12 weeks. For AS patients: • To evaluate the efficacy of R3R01 in reducing proteinuria at 12 weeks in the whole AS group. For FSGS patients: • To evaluate the efficacy of R3R01 in reducing proteinuria at 12 weeks in the whole FSGS group. |
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E.2.2 | Secondary objectives of the trial |
For all patients: • To evaluate improvement in quality of life for adults or the pediatric quality of life inventory for children (ages 12-18) and their parents, and assessing change from baseline to end of treatment and end of the follow-up period. • To evaluate the pharmacokinetics of R3R01 For AS patients: • To evaluate proteinuria complete response (UPCR <0.3g/g) at all timepoints proteinuria is measured • To evaluate proteinuria partial response (decrease in proteinuria from baseline of ≥50%) at all timepoints proteinuria is measured. For FSGS patients: • To evaluate proteinuria complete remission (UPCR <0.3g/g) at all timepoints proteinuria is measured • To evaluate proteinuria partial remission (decrease in proteinuria from baseline of ≥50% and an absolute value of UPCR < 3.0g/g at all timepoints proteinuria is measured To evaluate proteinuria modified partial remission (decrease of ≥40% and UPCR < 1.5g/g) at all timepoints proteinuria is measured |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All Patients: 1. Patient is able to communicate well with the investigator, understands and is willing to comply with all requirements of the study, and understands and signs the written informed consent form (ICF). 2. For children to be eligible, one or both parents must sign a parental permission form which provides information contained in the ICF. Children capable of assent must express their willingness to participate by signing an assent form. 3. Blood pressure in the normotensive or hypertensive range. 4. If patient has received a COVID vaccination, the baseline visit must occur at least one week or more after the second/booster vaccination. 5. Both female patients, as well as, female partners of male patients who are of child-bearing potential must be willing to not become pregnant for the complete duration of the study (>180 days) (90 days after the last dose of study medication). AS Inclusion Criteria (in addition): 6. Male and female patients from age 12 years and older, males and females with X-Linked AS and males and females with autosomal recessive AS. 7. Confirmed diagnosis of AS by genetic testing and /or kidney biopsy. 8. UPCR ≥1.0 g/g. 9. eGFR ≥ 45 mL/min/1.73m2. 10. ACEi/ARB therapy at maximum tolerated dose stable for at least 4 weeks prior to screening. ACEi/ARB dose should remain stable over the course of the study. FSGS Inclusion Criteria (in addition): 11. Male or female patients, 12 to 75 years old at the time of signing the informed consent. 12. Primary FSGS, i.e. without any identifiable cause, and confirmed by renal biopsy or documentation of a genetic mutation in a podocyte protein associated with FSGS. 13. Steroid-resistance defined as failure to achieve partial or complete remission, or experienced adverse events without acceptable clinical benefit after at least 8 weeks of adequate corticosteroid therapy for children and 12 weeks for adults. 14. UPCR between 3.5g/g and 12.0g/g. 15. eGFR > 45 mL/min/1.73m2. 16. If taking concomitant ACE and/or ARB treatment, it should remain at a stable dose for a minimum of 28 days prior to enrollment and during the course of the study. |
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E.4 | Principal exclusion criteria |
All Patients: 1. Uncontrolled diabetes mellitus as evidenced by an HbA1c ≥ 11%. 2. Uncontrolled hypertension a. Adults: (SBP ≥ 180mmHg and/or DBP ≥ 100mmHg). b. Children: ≥ 95th percentile or ≥ 130/80 mm Hg, whichever is lower, as defined in Appendix 13.8. 3. Moderate or severe hepatic impairment as per Child Pugh score (See Section 9.5.4.6) 4. Presence of any active (i.e., with symptoms) and/or uncontrolled infection (including COVID). 5. Human immunodeficiency virus (HIV). 6. BMI > 40. 7. History of malignancy other than treated basal cell or squamous cell skin cancer within the past 5 years. 8. History of alcohol abuse in the last 5 years or currently drinks in excess of 21 and 14 units per week for males and females, respectively. 9. Received an investigational agent within 30 days or 5 half-lives prior to screening (whichever is longer). 10. History of non-compliance such that patient is unlikely to be compliant with study visits, procedures or drug administration. 11. Patient has had an organ transplant, is currently on an organ transplant waiting list or there is a reasonable possibility that the patient will have an organ transplant in the 6 months after screening. 12. Participation in an interventional trial within the previous 3 months prior to screening or concurrent participation in a research trial. 13. Patient is not suitable to participate in the study for any reason (including, but not limited to co-morbidities, history of noncompliance with study visits, procedures, or drug administration) in the opinion of the investigator. 14. Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) are excluded from participation in the study unless they agree to use adequate contraception as described in Section 13.3. 15. Males who have no sterilization history and whose female partners have child-bearing potential, must agree to use highly effective method of contraception during the period from the time of signing the informed consent form (ICF) through 90 days after the last dose of study drug. They must agree to immediately inform the investigator if their partner becomes pregnant during the study. AS Exclusion Criteria (in addition): 16. Kidney disease apart from AS, e.g. diabetic nephropathy or lupus nephritis. 17. Bardoxolone treatment in the 90 days prior to screening. FSGS Exclusion Criteria (in addition): 18. Patient has collapsing variant of FSGS on renal biopsy. 19. Patient has FSGS secondary to another condition (e.g. obesity, cardiovascular, infectious, or autoimmune disorder). 20. Rituximab, cyclophosphamide or abatacept treatment in the 120 days prior to screening. If taking other chronic immuno-modulatory medications that are small molecules, the dosage must be stable for 4 weeks prior to screening. 21. If previous Rituximab treatment is greater than 120 days from screening, CD20 cell count should be within normal limits. 22. If previous other antibody treatment on a stable dose is greater than 120 days from screening, the investigator must deem administration of study drug to be safe. 23. SGLT2 inhibitors or sparsentan treatment in the 90 days prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability endpoints will be assessed by occurrence of adverse events (AE), changes in physical examinations, vital signs, ECGs and clinical laboratory parameters. Efficacy endpoint is change from baseline in UPCR after 12 weeks of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 |
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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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | 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 |
United States |
France |
Netherlands |
Germany |
Belgium |
United Kingdom |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |