A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Assess the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Profile of BI 764198 Administered Orally Once Daily for 12 Weeks in Patients With Focal Segmental Glomerulosclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 99
- 主要终点
- Achievement of at Least 25% Reduction in 24-hour Urine Protein Creatinine Ratio (UPCR) Relative to Baseline at Week 12
研究概览
简要总结
This study is open to adults with a type of kidney disease called focal segmental glomerulosclerosis (FSGS). The purpose of this study is to find out whether a medicine called BI 764198 improves the health of the kidneys in people with FSGS. Three different doses of BI 764198 are tested in this study.
Participants are put into 4 groups randomly, which means by chance. Three of the groups receive different doses of BI 764198 and one group receives placebo. Participants are in the study for about 4 months. For about 3 months, they take BI 764198 or placebo as capsules once a day.
Placebo capsules look like BI 764198 capsules but do not contain any medicine. Participants visit the study site about 10 times. You can participate in this study from your home. In this case a research nurse will visit you for the study visits.
Kidney health is assessed based on the analysis of urine samples, which participants collect at home. At the end of the study, the results are compared between the different groups. During the study, the doctors also regularly check the general health of the participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 Focal Segmental Glomerulosclerosis (FSGS) or documented Transient Receptor Potential Cation subfamily C Member 6 (TRPC6) gene mutation causing FSGS prior to screening visit.
- •Urine Protein-Creatinine Ratio (UPCR) ≥ 1000 mg/g based on first morning void urine sample during screening.
- •Patients treated with corticosteroids must be on a stable dose for at least 4 weeks prior to screening visit with no plan to change the dose until end of trial treatment.
- •Patients treated with Angiotensin Converting Enzyme (ACE) inhibitors, Angiotensin II Receptor Blockers (ARBs), finerenone, aldosterone inhibitors, or Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors should be on a stable dose for at least 4 weeks prior to screening visit with no plan to change the dose until end of trial treatment.
- •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) and in the study protocol.
- •Further inclusion criteria apply.
排除标准
- •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, Immunoglobulin A (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 dose throughout the study.
- •Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² at screening visit.
- •Time between start of the Q-wave and end of the T-wave in an electrocardiogram interval corrected for heart rate (QTc) intervals (QT interval corrected for heart rate using the method of Fridericia - QTcF) greater than 450 ms in males or greater than 470 ms in females, or any other clinically relevant electrocardiogram (ECG) findings (at the investigator's discretion) at screening visit.
- •Detection of graded cataract by Lens Opacities Classification System III (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 exclusion criteria apply.
研究组 & 干预措施
Placebo
Patients with primary focal segmental glomerulosclerosis (FSGS) or patients with monogenic FSGS as a result of TRPC6 mutations took daily one single capsule of placebo-matching BI 764198 orally for 12 weeks.
干预措施: Placebo (Drug)
BI 764198 20 mg
Patients with primary focal segmental glomerulosclerosis (FSGS) or patients with monogenic FSGS as a result of TRPC6 mutations took daily one single capsule of 20 milligrams (mg) of BI 764198 orally for 12 weeks.
干预措施: BI 764198 (Drug)
BI 764198 40 mg
Patients with primary focal segmental glomerulosclerosis (FSGS) or patients with monogenic FSGS as a result of TRPC6 mutations took daily one single capsule of 40 milligrams (mg) of BI 764198 orally for 12 weeks.
干预措施: BI 764198 (Drug)
BI 764198 80 mg
Patients with primary focal segmental glomerulosclerosis (FSGS) or patients with monogenic FSGS as a result of TRPC6 mutations took daily one single capsule of 80 milligrams (mg) of BI 764198 orally for 12 weeks.
干预措施: BI 764198 (Drug)
结局指标
主要结局
Achievement of at Least 25% Reduction in 24-hour Urine Protein Creatinine Ratio (UPCR) Relative to Baseline at Week 12
时间窗: At baseline and Week 12.
Predicted probability of patients as a percentage - predicted percentage of patients - achieving at least 25% reduction in 24-hour urine protein creatinine ratio (UPCR) relative to baseline at Week 12 (responders) is reported. Baseline was the average of two 24-hour urine samples collected before Visit 2 (Week 0). Patients who either missed their Week 12, 24-hour UPCR assessment or their Week 12, 24-hour UPCR assessment, occurred later than 5 days after the last dose (Residual Effect Period), were considered as non-responders. The predicted probability of response was calculated using a logistic regression utilizing corticosteroid use at randomization and baseline 24-hr UPCR as covariates and is presented as a percentage.
Relative Change From Baseline at Week 12 of 24-hour Urine Protein Creatinine Ratio (UPCR)
时间窗: At baseline and at Week 12.
Relative change from baseline at Week 12 in 24-hour urine protein creatinine ratio (UPCR), is reported. Baseline was the average of two 24-hour urine samples collected before Visit 2 (Week 0). An analysis of covariance (ANCOVA) model was used to estimate the relative change in UPCR from baseline to Week 12 with corticosteroid use at randomization and baseline 24-hr UPCR as covariates.
次要结局
- Change in 24-hour Urine Protein Creatinine Ratio (UPCR) Relative to Visit 3 at Week 12(At Week 1 and Week 12.)
- Change in 24-hour Urine Protein Creatinine Ratio (UPCR) Relative to Baseline at Week 13(At baseline and at Week 13.)
- Change in 24-hour Urinary Protein Excretion Relative to Baseline at Week 12(At baseline and at Week 12.)
- Pre-dose Plasma Concentration of BI 764198 at Steady-state (Cpre,ss ) at Week 4 and Week 12(At 671.917 hours and at 2015.917 hours after first drug administration.)