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Abstract: INFO29

Study Design of a Phase 2a trial of BI 764198, a Transient Receptor Potential Channel 6 (TRPC6) Inhibitor, in Focal Segmental Glomerulosclerosis

Session Information

  • Informational Posters
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • No subcategory defined

Authors

  • Gipson, Debbie, University of Michigan, Ann Arbor, Michigan, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
  • Desmond, Hailey, University of Michigan, Ann Arbor, Michigan, United States
  • Choi, Wansuk, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States
  • Manuel, Raymond, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States
  • Soleymanlou, Nima, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States
Description

Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage kidney disease and is characterised histopathologically by podocyte injury and depletion, resulting in significant proteinuria and progressive loss of kidney function. Transient receptor potential channel 6 (TRPC6) is thought to play an important role in podocyte health. In fact, TRPC6 gene variants exhibiting gain-of-function have been shown to be directly associated with familial forms of FSGS.
BI 764198 is a novel, selective, oral TRPC6 inhibitor that has been shown to be well tolerated in completed Phase I studies. The efficacy, safety, pharmacokinetic (PK) and pharmacodynamic profiles of BI 764198 are being assessed for the first time in patients with primary FSGS or those with TRPC6 monogenic disease in a Phase IIa proof-of-concept study (NCT05213624). This multicentre, randomised, double-blind, placebo-controlled trial is actively recruiting, with plans to enrol 60 patients across 45 sites in 12 countries. Patients will be randomised 1:1:1:1 to receive oral low, medium, high dose BI 764198 or placebo once daily for 12 weeks. Eligible patients must have a mean urinary protein:creatinine ratio (UPCR) ≥1500 mg/g at screening. Some study sites will be able to conduct visits at patients’ homes in a decentralised manner, allowing maximum flexibility in terms of patient recruitment, participation and retention.
The primary endpoint is the proportion of patients achieving ≥25% decrease in 24-hour UPCR from baseline to Week (W) 12. Secondary endpoints include change from baseline in UPCR at various time points (W4, 8, 12 and 13) and steady-state trough BI 764198 concentrations at W4 and 12 as a PK outcome. Further endpoints include change from baseline in eGFR at W12 and 13, change from baseline in urinary albumin:creatinine ratio at W4, 8, 12 and 13, safety findings and other PK parameters. In the US, selected study centres will partake in the NEPTUNE (Nephrotic Syndrome Study Network) programme. As such, this study, as a NEPTUNE-Match trial, will help generate data towards a precision medicine approach for the care of patients with FSGS and help inform target patient populations for future trials of BI 764198 in FSGS and other proteinuric diseases.

Funding

  • Boehringer Ingelheim
Abstract: INFO29

Study Design of a Phase 2a trial of BI 764198, a Transient Receptor Potential Channel 6 (TRPC6) Inhibitor, in Focal Segmental Glomerulosclerosis

Session Information

  • Informational Posters
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category:

  • No subcategory defined

Authors

  • Gipson, Debbie, University of Michigan, Ann Arbor, Michigan, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
  • Desmond, Hailey, University of Michigan, Ann Arbor, Michigan, United States
  • Choi, Wansuk, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States
  • Manuel, Raymond, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States
  • Soleymanlou, Nima, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States
Description

Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage kidney disease and is characterised histopathologically by podocyte injury and depletion, resulting in significant proteinuria and progressive loss of kidney function. Transient receptor potential channel 6 (TRPC6) is thought to play an important role in podocyte health. In fact, TRPC6 gene variants exhibiting gain-of-function have been shown to be directly associated with familial forms of FSGS.
BI 764198 is a novel, selective, oral TRPC6 inhibitor that has been shown to be well tolerated in completed Phase I studies. The efficacy, safety, pharmacokinetic (PK) and pharmacodynamic profiles of BI 764198 are being assessed for the first time in patients with primary FSGS or those with TRPC6 monogenic disease in a Phase IIa proof-of-concept study (NCT05213624). This multicentre, randomised, double-blind, placebo-controlled trial is actively recruiting, with plans to enrol 60 patients across 45 sites in 12 countries. Patients will be randomised 1:1:1:1 to receive oral low, medium, high dose BI 764198 or placebo once daily for 12 weeks. Eligible patients must have a mean urinary protein:creatinine ratio (UPCR) ≥1500 mg/g at screening. Some study sites will be able to conduct visits at patients’ homes in a decentralised manner, allowing maximum flexibility in terms of patient recruitment, participation and retention.
The primary endpoint is the proportion of patients achieving ≥25% decrease in 24-hour UPCR from baseline to Week (W) 12. Secondary endpoints include change from baseline in UPCR at various time points (W4, 8, 12 and 13) and steady-state trough BI 764198 concentrations at W4 and 12 as a PK outcome. Further endpoints include change from baseline in eGFR at W12 and 13, change from baseline in urinary albumin:creatinine ratio at W4, 8, 12 and 13, safety findings and other PK parameters. In the US, selected study centres will partake in the NEPTUNE (Nephrotic Syndrome Study Network) programme. As such, this study, as a NEPTUNE-Match trial, will help generate data towards a precision medicine approach for the care of patients with FSGS and help inform target patient populations for future trials of BI 764198 in FSGS and other proteinuric diseases.

Abstract: INFO29

Study Design of a Phase 2a trial of BI 764198, a Transient Receptor Potential Channel 6 (TRPC6) Inhibitor, in Focal Segmental Glomerulosclerosis

Session Information

  • Informational Posters
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category:

  • No subcategory defined

Authors

  • Gipson, Debbie, University of Michigan, Ann Arbor, Michigan, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
  • Desmond, Hailey, University of Michigan, Ann Arbor, Michigan, United States
  • Choi, Wansuk, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States
  • Manuel, Raymond, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States
  • Soleymanlou, Nima, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, United States
Description

Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage kidney disease and is characterised histopathologically by podocyte injury and depletion, resulting in significant proteinuria and progressive loss of kidney function. Transient receptor potential channel 6 (TRPC6) is thought to play an important role in podocyte health. In fact, TRPC6 gene variants exhibiting gain-of-function have been shown to be directly associated with familial forms of FSGS.
BI 764198 is a novel, selective, oral TRPC6 inhibitor that has been shown to be well tolerated in completed Phase I studies. The efficacy, safety, pharmacokinetic (PK) and pharmacodynamic profiles of BI 764198 are being assessed for the first time in patients with primary FSGS or those with TRPC6 monogenic disease in a Phase IIa proof-of-concept study (NCT05213624). This multicentre, randomised, double-blind, placebo-controlled trial is actively recruiting, with plans to enrol 60 patients across 45 sites in 12 countries. Patients will be randomised 1:1:1:1 to receive oral low, medium, high dose BI 764198 or placebo once daily for 12 weeks. Eligible patients must have a mean urinary protein:creatinine ratio (UPCR) ≥1500 mg/g at screening. Some study sites will be able to conduct visits at patients’ homes in a decentralised manner, allowing maximum flexibility in terms of patient recruitment, participation and retention.
The primary endpoint is the proportion of patients achieving ≥25% decrease in 24-hour UPCR from baseline to Week (W) 12. Secondary endpoints include change from baseline in UPCR at various time points (W4, 8, 12 and 13) and steady-state trough BI 764198 concentrations at W4 and 12 as a PK outcome. Further endpoints include change from baseline in eGFR at W12 and 13, change from baseline in urinary albumin:creatinine ratio at W4, 8, 12 and 13, safety findings and other PK parameters. In the US, selected study centres will partake in the NEPTUNE (Nephrotic Syndrome Study Network) programme. As such, this study, as a NEPTUNE-Match trial, will help generate data towards a precision medicine approach for the care of patients with FSGS and help inform target patient populations for future trials of BI 764198 in FSGS and other proteinuric diseases.