Health Condition 1: N041- Nephrotic syndrome with focal andsegmental glomerular lesions
Conditions
Interventions
Intervention1: BI 764198: Dose: 20 mg
Route: oral
Frequency: 1 tablet daily
Total duration of treatment: 104 weeks
Control Intervention1: Placebo to match BI 764198: Dose: matching placebo
Route: ora
Sponsors
Boehringer Ingelheim International GmbH
IQVIA RDS India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1.Signed and dated written informed consent or written informed consent provided by the participants legally accepted representative and assent provided by the participant (if applicable) at the time of informed consent signature in accordance with ICH-GCP and local legislation prior to admission to the trial. 2. Male or female participants more than equals to 12 years old on the day of signing informed consent or assent (Visit 1) 3. Weight of more than equals to 40 kg at the screening visit (Visit 1) 4. Body Mass Index (BMI) of less than equals to 40 kg per m2 at the screening visit (Visit 1) 5. Participants with a diagnosis prior to the screening visit (Visit 1) of either: a. Biopsy-confirmed pFSGS (as determined by the Investigator). The biopsy may have been conducted at any time in the past but should preferably include electron microscopy (EM) and immunofluorescence (IF) findings consistent with pFSGS. Enrollment can occur based on a light microscopy diagnosis of FSGS if EM and or IF analyses are unavailable, provided that the clinical history (nephrotic syndrome with hypoalbuminemia, immunosuppressive treatment) and disease progression support a diagnosis of pFSGS, and secondary causes identified by the exclusion criteria have been thoroughly excluded. OR b. Genetic FSGS resulting from a gain-of-function gene mutation in the TRPC6 gene (based on historical genetic test) 6. UPCR more than equals to 1500 mg per g based on the mean of the spot urine sample and first morning void urine sample (both assessed by central laboratory) at screening 7. Estimated glomerular filtration rate (eGFR) a. For adult participants (more than equals to 18 years) more than equals to 25 mL per min per 1.73 m2 (CKD-EPI formula based on serum cystatin C) at the screening visit (Visit 1) b. For adolescent participants (12 to less than 18 years); more than equals to 25 mL per min per 1.73 m2 based on CKiD U25 formula using height and serum cystatin C at the screening visit (Visit 1) 8. Seated blood pressure (mean of 3 values) SBP less than equals to 160 mmHg (adult participants aged more than equals to 18) or SBP less than equals to 140 mmHg (adolescent participants aged 12 to less than 18 years) at the screening visit (Visit 1). A participant with a documented history of white coat hypertension may be included, as long as the patient is considered medically stable by the investigator and true blood pressure can be considered to be less than equals to 160 mmHg (adult participants aged more than equals to 18 years) or less than equals to 140 mmHg (adolescent participants aged 12 to less than 18 years) 9. Participants should be treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) at stable and maximum tolerated dose for at least 8 weeks prior to the screening visit (Visit 1), preferably with no plan to change the dose until the end of the randomised treatment period (i.e. EoT, Week 104) unless not tolerated or indicated as per the discretion of the investigator 10. If treated with (non-steroidal) MRA, ERA, GLP1-Ra or SGLT2i, participants must be on a stable and optimised dose for at least 8 weeks prior to the screening visit (Visit 1), preferably with no plan to change the dose until the end of the randomised treatment period (i.e. EoT, Week 104) 11. If treated with oral immu
Exclusion criteria
Exclusion criteria: 1. Known monogenic or syndromic causes of FSGS (with the exception of TRPC6 gain-of function gene mutations) 2. Clinical or histologic evidence of secondary adaptive or toxic forms of FSGS (based on Investigators judgement to decide whether FSGS is secondary to the causes listed below. Patients considered to have primary FSGS that suffer comorbidities that are associated with secondary forms of FSGS are eligible as long these are not considered causative for FSGS), including (see also KDIGO guideline [R22-1394]) FSGS secondary to an identifiable adaptive pathophysiological cause (either reduced nephron mass or increased workload per nephron, example T2D, hypertension, obesity, solitary kidney, reflux nephropathy) FSGS secondary to alterations of glomerular epithelial cells (i.e. drug [e.g. mTOR inhibitors, lithium, interferon, heroin], toxin and viral [example HIV, CMV] induced) 3. FSGS of undetermined cause (FSGS-UC) with a diagnosis prior to the screening visit (Visit 1) (based on Investigators judgement) 4. A history of organ transplantation or planned organ transplantation during the course of the trial 5. Use of intravenous immunosuppressive agents (example cyclophosphamide, rituximab, obinutuzumab) in the last 6 months prior to screening (Visit 1) 6. Treatment with metformin or dofetilide (sensitive MATE1 substrates) within one week prior to the randomisation visit (Visit 2) 7. Treatment with strong inhibitors or strong inducers of CYP3A4 per 5 within one week or 5 half-lives (whichever is longer) prior to the randomisation visit (Visit 2) 8. Alanine aminotransferase (ALT) per aspartate aminotransferase (AST) more than 3X the upper limit of normal (ULN) at the screening visit (Visit 1) 9. Clinically significant laboratory abnormalities or medical conditions during screening which pose a safety risk for the participant or may interfere with the trial objectives, in the Investigator s opinion (except for renal function tests or deviation of clinical laboratory values that are related to FSGS). 10. Glucocorticoid-naive patients unless glucocorticoid treatment is not indicated (example FSGS due to TRPC6 gain-of-function gene mutation) or tolerated (example due to expected side effects) 11. QTc intervals (QTcF) greater than 450 ms in males or greater than 470 ms in females, or any other clinically relevant ECG findings (in the Investigators opinion) at the screening visit (Visit 1) 12. History of congenital long QT syndrome 13. A history of gastrointestinal (GI) surgery or GI disorders that could interfere with absorption of the trial medication, in the Investigators opinion 14. Major surgery (major, in the Investigators opinion) performed within 3 months prior to the screening visit (Visit 1) or planned within 6 months after randomisation (Visit 2) 15. Any documented active or suspected malignancy. Any history of malignancy within 5 years prior to the screening visit (Visit 1), except effectively treated non-melanoma skin cancers, in situ carcinoma of the uterine cervix, breast ductal carcinoma in situ, other malignancy that is considered cured by local SOC treatment. 16. History of relevant allergy or hypersensitivity, in the Investigators opinion (example systemic hypersensitivity reactions including anaphylaxis and anaphylactoid reactions to the trial medication excipients) 17. Participants who m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| to demonstrate superiority of BI 764198 for the mean relative change from baseline to Week 104 in 24-hr urinary protein-to-creatinine ratio (UPCR, measured in mg per g) in participants with pFSGS or those with gain-of-function gene mutations, some of whom are on background calcineurin inhibitor (CNI) treatment.Timepoint: week 104 | — |
Secondary
| Measure | Time frame |
|---|---|
| to estimate the difference between BI 764198 and placebo in the mean absolute change in eGFR based on serum cystatin C (eGFRcys, measured in mL per min per 1.73m2) from baseline to Week 104 in participants with pFSGS, or those with TRPC6 gain-of-function gene mutation, some of whom are on background CNI treatment.Timepoint: week 104 | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Croatia, Denmark, France, Germany, Greece, Hong Kong, India, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Republic of Korea, Romania, Singapore, Slovakia, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States of America
Contacts
Public ContactShweta Pradhan
IQVIA RDS (India) Private Limited
Outcome results
None listed