E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Injuries, poisonings, and occupational diseases [C21] |
MedDRA Classification |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objectives of this study are to investigate safety, tolerability, and the pharmacokinetic and pharmacodynamic profile of BI 764198 vs. placebo administered orally once daily for 12 weeks in patients with primary FSGS or with TRPC6 mutations causing FSGS. |
Les objectifs principaux de cette étude sont d’évaluer la sécurité, la tolérance et le profil pharmacocinétique et pharmacodynamique des doses de 20mg, 40mg et 80mg de BI 764198, administrées par voie orale une fois par jour pendant 12 semaines, comparées au placebo chez les patients atteints de FSGS primaire ou FSGS dues à des mutations du TRPC6 |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female patients 18 years to 75 years (both inclusive) of age on the day of signing informed consent. - Patients diagnosed with biopsy proven primary FSGS or documented TRPC6 gene mutation causing FSGS prior to screening visit. - Average UPCR ≥ 1500 mg/g based on two 24 hour urine samples collected at least 7 days apart at screening. - Completion of initial corticosteroid therapy course (if applicable) or discontinuation due to intolerance before entry to the trial. - If applicable, corticosteroid therapy (i.e. prednisone) of ≤15 mg/day or ≤30 mg on alternate days with stable dose for at least 2 weeks at randomization, with no plan to change the dose during the study. - Patients treated with ACE inhibitors, ARBs, finerenone, aldosterone inhibitors, or SGLT2 inhibitors should be on a stable dose for at least 4 weeks prior to screening visit with no plan to change the dose during the study. - Body Mass Index (BMI) of ≤ 40 kg/m2 at screening visit. - Women of childbearing potential (WOCBP) must be willing and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the informed consent form (ICF). Men must be willing and able to use condom if their partner is a WOCBP.
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E.4 | Principal exclusion criteria |
- Known monogenic (with the exception of TRPC6 gene mutations) or clinical or histologic evidence of secondary FSGS. - Documented Alport syndrome, Nail Patella syndrome, diabetic nephropathy, IgA nephropathy, lupus nephritis, or monoclonal gammopathy (e.g., multiple myeloma). - Concomitant use of calcineurin inhibitors. - Concomitant treatment with cytotoxic agents (cyclophosphamide, chlorambucil), or CD20 monoclonal antibody, e.g., rituximab, within 5 half-lives before screening visit. Note: use of other immunosuppression therapies considered as standard of care may be allowed as long as the patient remains on stable therapeutic dose throughout the study. - Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (CKD EPI formula based on serum creatinine and cystatin C) at screening visit. - Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >3X the upper limit of normal (ULN) at screening visit. - QTc intervals (QTcF) greater than 450 ms in males or greater than 470 ms in females, or any other clinically relevant ECG findings (at the investigator’s discretion) at screening visit. - Detection of graded cataract by LOCS III higher than NC1/NO1, C0, P0 in the slit lamp eye examination at screening visit. Planned cataract surgery during participation in the study. Patients with cataract who have undergone lens replacement are not excluded. - Women who are pregnant, nursing, or who plan to become pregnant while in the study.
Further criteria apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Patients achieving at least 25% reduction in 24-hour urine proteincreatinine ratio (UPCR) relative to baseline (visit 3) at week 12. |
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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) |
1) Change in UPCR relative to baseline (visit 3) at weeks 4, 8, and 12 2) Change in UPCR relative to screening at week 13 3) Change in 24-hour urinary protein excretion relative to screening at week 12 4) The following pharmacokinetic parameters of BI 764198 will be determined if feasible: - Steady state trough concentration Cpre,ss on week 4 and week 12 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) weeks 4,8, and 12 2) week 13 3) week 12 4) weeks 4 and 12 |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | 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 | 4 |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Australia |
United States |
Belgium |
France |
Germany |
Hungary |
Ireland |
Italy |
United Kingdom |
Spain |
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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 | |
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 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 24 |