Focal Segmental Glomerulosclerosis
Conditions
Brief summary
PODOMOUNT-pFSGS This study is open to adults and adolescents with a kidney condition called focal segmental glomerulosclerosis (FSGS). The purpose of this study is to find out whether a medicine called BI 764198 helps people with FSGS. Participants are put into 2 groups randomly, which means by chance. Every participant has an equal chance of being in each group. One group takes BI 764198 tablets, and the other group takes placebo tablets. Placebo tablets look like BI 764198 tablets but do not contain any medicine. Participants take a tablet once a day for up to 2 years. All participants also continue their standard medication for FSGS. Participants are in the study for up to 2 years. During this time, they visit the study site about every 3 months. Participants regularly collect urine samples. This is done to check their kidneys. The results are compared between the two groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.
Interventions
DRUGBI 764198
BI 764198
DRUGPlacebo
Placebo matching BI 764198
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participants ≥12 years old on the day of signing informed consent/assent (Visit 1) 2. Weight of ≥40 kg at the screening visit (Visit 1) 3. Body mass index (BMI) of ≤40 kg/m² at the screening visit (Visit 1) 4. Participants with a diagnosis prior to the screening visit (Visit 1) of either: * Biopsy-confirmed primary focal segmental glomerulosclerosis (pFSGS) (based on Investigator's judgement) OR * Genetic focal segmental glomerulosclerosis (FSGS) resulting from a gain-of-function mutation in the transient receptor potential cation subfamily C member 6 (TRPC6) gene (based on historical genetic test) 5. Urine protein-creatinine ratio (UPCR) ≥1500 mg/g based on the mean of the spot urine sample and first morning void (FMV) urine sample (both assessed by central laboratory) at the screening visit (Visit 1) 6. Estimated glomerular filtration rate (eGFR) * For adult participants (≥18 years): ≥25 mL/min/1.73 m² (chronic kidney disease epidemiology collaboration (CKD-EPI) formula based on serum cystatin C) at the screening visit (Visit 1) * For adolescent participants (12 to \<18 years): ≥25 mL/min/1.73 m² based on chronic kidney disease under 25 years (CKiD U25) formula using serum cystatin C at the screening visit (Visit 1) Further inclusion criteria apply.
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 Investigator's judgement) 3. FSGS of undetermined cause (FSGS-UC) with a diagnosis prior to the screening visit (Visit 1) (based on Investigator's judgement) 4. A history of organ transplantation or planned organ transplantation during the course of the trial 5. Use of intravenous immunosuppressive agents (e.g. cyclophosphamide, rituximab, obinutuzumab) in the last 6 months prior to screening (Visit 1) Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative change in 24-hour UPCR (measured in mg/g) from baseline to Week 104 | Baseline and Week 104 | 24-hour urinary protein-to-creatinine ratio (24-hr UPCR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Key secondary endpoint: Absolute change in eGFRcys in mL/min/1.73m2 from baseline to Week 104 | Baseline and Week 104 | Estimated glomerular filtration rate based on serum cystatin C (eGFRcys) |
| Key secondary endpoint: Treatment response, defined as 24-hr UPCR <1000 mg/g at Week 104 | At Week 104 | 24-hour urinary protein-to-creatinine ratio (24-hr UPCR) |
| Treatment response, defined as 24-hr UPCR <1000 mg/g and eGFRcys ≥85% vs. baseline at Week 104 and no treatment failure between randomisation and Week 104 (combined or multi-component endpoint) | At Week 104 | Treatment failure defined as: Use of rescue therapy (treatment escalation): \- Worsening or severely active disease resulting in investigator-determined treatment failure and requiring rescue therapy (treatment escalation) during the trial. Treatment escalation includes initiation of a new medication or intensification of existing therapy, including an increase in the dose or target peak/trough level of selected concomitant medications (immunosuppressive therapies). Examples of intensification of immunosuppressive therapies used at screening, include: * calcineurin inhibitors (CNIs) * anti-metabolites (azathioprine, mycophenolate mofetil) * cytotoxic agents (cyclophosphamide, chlorambucil) * glucocorticoids, including escalation of prednisolone to ≥20 mg/day (oral or intravenous), or equivalent, for \>14 days for treatment of kidney disease. |
| Complete remission, defined as 24-hr UPCR <300 mg/g at Week 104 | At Week 104 | 24-hour urinary protein-to-creatinine ratio (24-hr UPCR) |
| Change from baseline across disease-specific clinical outcome assessment (COA) NS-SIM-PRO at Week 104 | Baseline and Week 104 | The nephrotic syndrome swelling impact measure (NS-SIM-PRO) has 23 items covering physical function (e.g. mobility), physical symptoms (e.g. fatigue, nausea), and essential function (e.g. vision) impacts identified as being important aspects of participants' experiences with nephrotic-syndrome related swelling. It is expected that all item responses will be combined to generate a single score representing overall swelling impact. The score ranges from 0 up to 4 (0 = never, 1 = almost never, 2 = sometimes, 3 = often, 4 = almost always). A lower score on any of the NS-SIM-PRO subscales indicate a better quality of life. |
| Change from baseline across clinical outcome assessment (COA) KDQOL-36 at Week 104 | Baseline and Week 104 | Kidney disease quality of life 36-item short form survey (KDQOL-36) assessing the health-related quality of life (HRQOL) in adult participants with kidney disease. It combines the generic SF-12 Health Survey with additional items specifically relevant to kidney disease. Key Components: * SF-12 Health Survey: Includes 12 items that measure physical and mental health, providing a broad overview of the patient's general health status. * Burden of Kidney Disease: This subscale (4 items) assesses how much kidney disease interferes with daily life and causes frustration. * Symptoms/Problems: This subscale (12 items) evaluates the frequency and severity of symptoms related to kidney disease, such as pain, fatigue, and sleep disturbances. * Effects of Kidney Disease: This subscale (8 items) measures the impact of kidney disease on daily activities and overall well-being. The score ranges from 0 up to 6 and a higher score on most of the KDQOL-36 subscales indicate a better quality of life. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Denmark, Estonia, Finland, France, Georgia, Germany, Greece, Hong Kong, India, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Portugal, Romania, Saudi Arabia, Singapore, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTBoehringer Ingelheim
Outcome results
None listed