Clinical trial NCT04387448: A Study of TRPC5 Channel Inhibitor in Patients With Diabetic Nephropathy, Focal Segmental Glomerulosclerosis, and Treatment-Resistant Minimal Change Disease
Official title: A Phase 2a Multiple Ascending, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GFB-887, a TRPC5 Channel Inhibitor, in Patients With Diabetic Nephropathy, Focal Segmental Glomerulosclerosis, and Treatment-Resistant Minimal Change Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Kidney Diseases
Diabetic Nephropathies
Glomerulosclerosis, Focal Segmental
Nephrosis, Lipoid
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Glomerulonephritis
Nephritis
Nephrosis
Lead sponsor: Goldfinch Bio, Inc.
Sponsor class: INDUSTRY
First posted: 2020-05-13
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multiple-ascending, placebo-controlled
Primary purpose: TREATMENT

Brief summary: This is a phase 2a study evaluating the safety and tolerability of multiple ascending doses of GFB-887 in patients with diabetic nephropathy (DN), focal segmental glomerulosclerosis (FSGS), and treatment-resistant minimal change disease (TR-MCD).

Detailed description: Approximately 125 patients will be enrolled in this study across the United States. Patients with DN and FSGS/TR-MCD will be randomized in 3 ascending dose cohorts to receive either GFB-887 or placebo.

Eligibility criteria: Inclusion Criteria:

* All patients:

  1. Male or female 18-75 years of age, of any race, at the time of signing informed consent.
  2. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 at Screening.
  3. Currently receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).
* For DN patients:

  1. Diagnosis of type 2 diabetes with glycated hemoglobin (HbA1c) level ≤11% at Screening.
  2. UACR ≥ 150 mg/g.
* For FSGS/TR-MCD patients:

  1. Diagnosis of FSGS based on either biopsy or genetic testing or TR-MCD based on biopsy.
  2. UPCR ≥ 1.0 g/g.

Exclusion Criteria:

* All patients:

  1. Evidence of another (non-DN, non-FSGS/TR-MCD, respectively) kidney disease.
  2. History of malignancy, unless in remission for at least 5 years other than adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or prostate cancer not expected to require treatment over the course of the study.
  3. History of any organ or bone marrow transplant, including kidney grafts.
  4. History of alcoholism or drug/chemical abuse within 12 months prior to Screening.
* For DN patients:

  1. Renal disease that requires immunosuppressive therapy (currently, or in the past).
  2. Body mass index (BMI) \>45 kg/m2.
* For FSGS/TR-MCD patients:

  1. Currently on calcineurin inhibitors or history of resistance to calcineurin inhibitors.
  2. Body mass index (BMI) \>40 kg/m2.
  3. Known history of severe or chronic hepatobiliary disease.

Primary outcomes:
measure: Percentage change in Urine Protein-to-Creatinine Ratio (UPCR)
timeFrame: 12 weeks
measure: Percentage change in Urine Albumin-to-Creatinine Ratio (UACR)
timeFrame: 12 weeks
Secondary outcomes:
measure: Proportion of FSGS/TR-MCD patients achieving a modified partial remission
timeFrame: 12 weeks
measure: Proportion of FSGS/TR-MCD patients achieving a complete remission
timeFrame: 12 weeks
measure: Percentage change in 24-hour urine protein excretion
timeFrame: 12 weeks
measure: Percentage change in 24-hour urine albumin excretion
timeFrame: 12 weeks
measure: Proportion of patients (DN or FSGS/TR-MCD) with a UACR/UPCR decrease of at least 30% of baseline
timeFrame: 12 weeks
measure: Proportion of patients (DN or FSGS/TR-MCD) with a UACR/UPCR decrease of at least 40% of baseline
timeFrame: 12 weeks
measure: Proportion of patients (DN or FSGS/TR-MCD) with a UACR/UPCR decrease of at least 50% of baseline
timeFrame: 12 weeks
measure: Incidence and severity of adverse events
timeFrame: 12 weeks
measure: Incidence of clinically significant changes in 12-lead electrocardiogram (ECG) parameters, vital signs measurements, and physical examinations
timeFrame: Approximately 12 weeks
measure: Incidence of clinically significant changes in laboratory parameters
timeFrame: 12 weeks
measure: Plasma pharmacokinetics (PK) parameters: maximum observed plasma concentration (Cmax)
timeFrame: 12 weeks
measure: Plasma PK parameters: time of the observed plasma concentration (Tmax)
timeFrame: 12 weeks
measure: Plasma PK parameters: area under the plasma concentration-time curve (AUC)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mesa
country: United States
facility: Aventiv Research - Phoenix
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Kidney Disease & Hypertension Centers (AKDHC)
state: Arizona
city: Glendale
country: United States
facility: Academic Medical Research Institute (AMRI)
state: California
city: Granada Hills
country: United States
facility: Amicis Research Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Northridge
country: United States
facility: Valley Renal Medical Group
state: California
city: Palm Springs
country: United States
facility: Respire Research - Palm Springs
state: California
city: S. Gate
country: United States
facility: Dr. Malvin Yan Inc.
state: California
city: San Dimas
country: United States
facility: North American Research Institute
state: California
city: Tarzana
country: United States
facility: Valiance Clinical Research - Tarzana
state: California
city: Vacaville
country: United States
facility: Amicis Research Center
state: California
city: Victorville
country: United States
facility: DaVita Mojave Sage Dialysis
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Denver
country: United States
facility: Colorado Kidney Care (Denver Nephrology)
state: Colorado
city: Wheat Ridge
country: United States
facility: Western Nephrology - Westminster
state: Colorado
city: Hartford
country: United States
facility: DaVita Hartford North
state: Connecticut
city: Newark
country: United States
facility: Nephrology Associationes, P.A.
state: Delaware
city: Doral
country: United States
facility: Prohealth Research Center - Doral
state: Florida
city: Leesburg
country: United States
facility: Clinical Site Partners Leesburg, LLC
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute
state: Florida
city: Miami
country: United States
facility: Kidney & Hypertension Specialists of Miami
state: Florida
city: Pensacola
country: United States
facility: Avanza Medical Research Center
state: Florida
city: Port Charlotte
country: United States
facility: Coastal Nephrology Associates Research Center, LLC
state: Florida
city: Winter Park
country: United States
facility: Florida Premier Research Institute - Clay Street
state: Florida
city: Augusta
country: United States
facility: Masters of Clinical Research, Inc.
state: Georgia
city: Tyrone
country: United States
facility: Inova Clinical Trials and Research Center
state: Georgia
city: Meridian
country: United States
facility: Boise Kidney and Hypertension Institute
state: Idaho
city: Chicago
country: United States
facility: Research by Design, LLC
state: Illinois
city: Hinsdale
country: United States
facility: Adventist Health Partners
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa College of Public Health
state: Iowa
city: Manhattan
country: United States
facility: My Kidney Center, LLC
state: Kansas
city: Lafayette
country: United States
facility: Louisiana Kidney Update, LLC
state: Louisiana
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center - School of Medicine - New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Renal and Transplant Associates of New England, PC
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Wayne State University School of Medicine
state: Michigan
city: Roseville
country: United States
facility: St. Clair Nephrology
state: Michigan
city: Edina
country: United States
facility: DaVita Clinical Research
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota - Center for Pediatric Obesity Medicine
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Tupelo
country: United States
facility: Nephrology & Hypertension Associates Ltd
state: Mississippi
city: Kansas City
country: United States
facility: Clinical Research Consultants
state: Missouri
city: Las Vegas
country: United States
facility: DaVita Pelican Point Dialysis
state: Nevada
city: Reno
country: United States
facility: Sierra Nevada Nephrology Consultants
state: Nevada
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New Bern
country: United States
facility: Eastern Nephrology Associates PLLC
state: North Carolina
city: Akron
country: United States
facility: Akron Nephrology Associates, Inc.
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Orangeburg
country: United States
facility: South Carolina Nephrology and Hypertension
state: South Carolina
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University Health Sciences Center - Amarillo
state: Texas
city: Arlington
country: United States
facility: Arlington Nephrology, PC
state: Texas
city: Conroe
country: United States
facility: Conroe Willis Medical Research
state: Texas
city: Dallas
country: United States
facility: Renal Disease Research Institute
state: Texas
city: El Paso
country: United States
facility: El Paso Kidney Specialists, PA
state: Texas
city: Houston
country: United States
facility: Xpress Trials LLC
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Lewisville
country: United States
facility: North Texas Kidney Disease Association
state: Texas
city: San Antonio
country: United States
facility: Clinical Advancement Center, PLLC
state: Texas
city: San Antonio
country: United States
facility: San Antonio Kidney Disease Center Physicians Group, PLLC
state: Texas
city: Webster
country: United States
facility: Clear Lake Specialties
state: Texas
city: Salt Lake City
country: United States
facility: Utah Kidney Research Institute
state: Utah
city: Norfolk
country: United States
facility: Tidewater Kidney Specialists - Riverview
state: Virginia
city: Spokane
country: United States
facility: Providence Medical Research Center
state: Washington
Study officials:
References: