A Study to Test BI 764198 in People With a Type of Kidney Disease Called Focal Segmental Glomerulosclerosis

NCT05213624 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 1434-00042020-000384-23U1111-1292-1333
• Study Type: interventional
• Target: 67
• Locations: 10 countries
• Sites: 54

Brief Summary

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.

Conditions

Kidney Disease, Chronic

Outcome Measures

Primary Outcomes (2)

• Achievement of at Least 25% Reduction in 24-hour Urine Protein Creatinine Ratio (UPCR) Relative to Baseline at 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.

  At baseline and Week 12.

• Relative Change From Baseline at Week 12 of 24-hour Urine Protein Creatinine Ratio (UPCR)

  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.

  At baseline and at Week 12.

Secondary Outcomes (4)

• 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.

Study Arms (4)

BI 764198 20 mg

EXPERIMENTAL

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.

Drug: BI 764198

BI 764198 40 mg

EXPERIMENTAL

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.

Drug: BI 764198

BI 764198 80 mg

EXPERIMENTAL

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.

Drug: BI 764198

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

BI 764198 DRUG

One single capsule of 20 milligrams (mg), 40 mg, or 80 mg of BI 764198 orally, once a day.

BI 764198 20 mg; BI 764198 40 mg; BI 764198 80 mg

Placebo DRUG

One single capsule of placebo matching BI 764198 orally, once a day.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (54)

Nephrology Consultants, LLC

Huntsville, Alabama, 35805, United States

Location

University of California San Francisco

San Francisco, California, 94121, United States

Location

Valiance Clinical Research-South Gate-67878

South Gate, California, 90280-5219, United States

Location

Valiance Clinical Research-Tarzana-68237

Tarzana, California, 91356, United States

Location

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Elixia Fort Lauderdale, LLC

Fort Lauderdale, Florida, 33308, United States

Location

South Florida Research Institute

Lauderdale Lakes, Florida, 33313, United States

Location

Total Research Group, LLC

Miami, Florida, 33126, United States

Location

Emory Children's Center

Atlanta, Georgia, 30322, United States

Location

NANI Research, LLC

Oak Brook, Illinois, 60523, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Tech University Health Sciences Center-Amarillo-63885

Amarillo, Texas, 79106, United States

Location

Dallas Nephrology Associates Medical Clinic

DeSoto, Texas, 75115-2011, United States

Location

Prolato Clinical Research Center-Houston-68087

Houston, Texas, 77054, United States

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Griffith Health

Southport, Queensland, 4125, Australia

Location

Sunshine Hospital

AT Albans, Victoria, 3021, Australia

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Fu Yang people's Hospital

Fuyang, 236000, China

Location

Guangdong Provincial People's Hospital

Guangzhou, 510080, China

Location

The First Afiliated Hospital, Sun Yet-sen University

Guangzhou, 510080, China

Location

Zhejiang Province People's Hospital

Hangzhou, 310014, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, 330006, China

Location

The First People's Hospital of Nanning

Nanning, 530000, China

Location

Tongren hospital, Shanghai Jiaotong University School of Medicine

Shanghai, 200051, China

Location

Shanghai Fifth People's Hospital affiliated to Fudan University

Shanghai, 200240, China

Location

HOP Pellegrin

Bordeaux, 33076, France

Location

HOP Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

HOP Hôtel-Dieu

Nantes, 44093, France

Location

Universitätsklinikum Köln (AöR)

Cologne, 50937, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

A.O. Policlinico Giovanni XXIII di Bari

Bari, 70124, Italy

Location

Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

Location

Fondazione Salvatore Maugeri

Pavia, 27100, Italy

Location

New Zealand Clinical Research (ChristChurch)

Christchurch, 8011, New Zealand

Location

Dunedin Hospital

Dunedin, 9016, New Zealand

Location

Hospital Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Fundació Puigvert

Barcelona, 08025, Spain

Location

Hospital Universitari Vall D Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

St Luke's Hospital

Bradford, BD5 0NA, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Salford Royal

Salford, M6 8HD, United Kingdom

Location

Related Publications (3)

• Trachtman H, Kretzler M, Gesualdo L, Cross N, Workeneh B, Kaufeld J, Meijers B, Ye Z, Chen Q, Derebail VK, Ng MSY, Ji B, Lobmeyer MT, Retlich S, Licariao Rocha FT, Prasad S, Soleymanlou N. TRPC6 inhibition for the treatment of focal segmental glomerulosclerosis: a randomised, placebo-controlled, phase 2 trial of BI 764198. Lancet. 2026 Feb 7;407(10528):587-598. doi: 10.1016/S0140-6736(25)02255-X. Epub 2026 Jan 27.

  PMID: 41616795 DERIVED

• Wooden B, Beenken A, Martinelli E, Saida K, Knob AL, Ke J, Pisani I, Jin G, Lane B, Mitrotti A, Colby E, Lim TY, Guglielmi F, Osborne AJ, Ahram DF, Wang C, Armand F, Zanoni F, Bomback AS, Delsante M, Appel GB, Ferrari MRA, Martino J, Sahdeo S, Breckenridge D, Petrovski S, Paul DS, Hall G, Magistroni R, Murtas C, Feriozzi S, Rampino T, Esposito P, Helmuth ME, Sampson MG, Kretzler M, Kiryluk K, Shril S, Gesualdo L, Maggiore U, Fiaccadori E, Gbadegesin R, Santoriello D, D'Agati VD, Saleem MA, Gharavi AG, Hildebrandt F, Pollak MR, Goldstein DB, Sanna-Cherchi S. Natural History and Clinicopathological Associations of TRPC6-Associated Podocytopathy. J Am Soc Nephrol. 2025 Feb 1;36(2):274-289. doi: 10.1681/ASN.0000000501. Epub 2024 Oct 1.

  PMID: 39352759 DERIVED

• Salemkour Y, Yildiz D, Dionet L, 't Hart DC, Verheijden KAT, Saito R, Mahtal N, Delbet JD, Letavernier E, Rabant M, Karras A, van der Vlag J, Nijenhuis T, Tharaux PL, Lenoir O. Podocyte Injury in Diabetic Kidney Disease in Mouse Models Involves TRPC6-mediated Calpain Activation Impairing Autophagy. J Am Soc Nephrol. 2023 Nov 1;34(11):1823-1842. doi: 10.1681/ASN.0000000000000212. Epub 2023 Sep 6.

  PMID: 37678257 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2022
• First Posted: January 28, 2022
• Study Start: May 3, 2022
• Primary Completion: January 3, 2025
• Study Completion: January 3, 2025
• Last Updated: January 12, 2026
• Results First Posted: January 12, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Locations

CN (8); NZ (2); AU (5); BE (1); DE (3); US (20); IT (3); FR (3); GB (3); ES (6)