Clinical trial NCT03217591: A Study to Evaluate the Soluble Guanylate Cyclase (sGC) Stimulator IW-1973 in Diabetic Nephropathy / Diabetic Kidney Disease as Measured by Albuminuria
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of IW-1973 in Patients With Type 2 Diabetes With Albuminuria Treated With Renin-Angiotensin System Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus With Diabetic Nephropathy
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Cyclerion Therapeutics
First posted: 2017-07-14
Enrollment: 156
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 2, randomized, double-blind, placebo-controlled, parallel-group study
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of IW-1973 in patients with type 2 diabetes mellitus with albuminuria who are on a stable regimen of renin-angiotensin system inhibitors.


Eligibility criteria: Key Inclusion Criteria:

* Patient is an ambulatory male or female from 25 to 75 years old at the Screening Visit.
* Patient has type 2 diabetes diagnosed by a physician or nurse practitioner ≥6 months before the Screening Visit, has been on ≥1 antihyperglycemic medication for ≥12 weeks preceding the Randomization Visit, and has been on a stable regimen (ie, same drug and same dose) of ≥1 antihyperglycemic medication for ≥28 days preceding the Randomization Visit. (Modification of short-acting insulin throughout the Screening Period will not affect eligibility.)
* Patient has been on a stable regimen (ie, same drug and dose) of antihypertensive medications, which must include an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB), for ≥28 days preceding the Randomization Visit and is expected to remain on their regimen through the Follow-up Visit.
* Patient has the following:

  1. Estimated glomerular filtration rate (eGFR) 30 to 75 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (1) at the Screening and Baseline Visits
  2. Urine albumin-to-creatinine ratio (UACR) \>200 mg/g at the Screening and Baseline Visits and \<5000 mg/g at Screening and Baseline Visits
  3. Serum albumin \>3.0 g/dL at the Screening and Baseline Visits
  4. Hemoglobin A1c (HbA1c) ≤11% at the Screening and Baseline Visits
  5. Systolic blood pressure (BP) of 110 to 160 mm Hg at the Screening and Baseline Visits
* Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 60 days after the final dose of study drug.
* Male patients must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception from the Screening Visit through 60 days after the final dose of study drug.
* Other inclusion criteria per protocol.

Key Exclusion Criteria:

* Patient has a history of secondary hypertension (ie, renal artery stenosis, primary aldosteronism, or pheochromocytoma).
* Patient has a body mass index (BMI) \<20 or \>45 kg/m2 at the Screening Visit.
* Patient has a history of platelet dysfunction, hemophilia, von Willebrand disease, coagulation disorder, other bleeding diathesis, or significant, nontraumatic bleeding episode(s), such as from a gastrointestinal source.
* Patient has hepatic impairment defined as Child-Pugh A, B, C.
* Patient has significant comorbidities (eg, malignancy, advanced liver disease, pulmonary hypertension, pulmonary fibrosis, lung disease requiring supplemental oxygen) or other significant conditions that, in the Investigator's opinion, would limit the patient's ability to complete or participate in this clinical study; has been hospitalized for cardiovascular, renal, or metabolic cause in the 3 months before the Screening Visit; or has a life expectancy of less than 1 year.
* Patient has had prior dialysis, renal transplant, or planned renal transplant.
* Patient has clinically active, symptomatic, or unstable coronary artery or heart disease within the 3 months before the Screening Visit, defined as 1 of the following:

  1. Hospitalization for myocardial infarction (MI), unstable angina, or heart failure
  2. New-onset angina with positive functional study or coronary angiogram revealing stenosis
  3. Coronary revascularization procedure
* Patient has a history of clinically significant hypersensitivity or allergies to any of the inactive ingredients contained in the active or placebo drug products.
* Patient has previously received IW-1973 in a study, or received an investigational drug during the 30 days or 5 half-lives of that investigational drug (whichever is longer) before the Screening Visit, or is planning to receive another investigational drug at any time during the study.
* Patient is taking specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific inhibitors of PDE5 (including dipyridamole and theophylline), any supplements for the treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide (NO) donors in any form. These medications and supplements are prohibited from 7 days before Randomization through the duration of the study.
* Patient is taking strong cytochrome P450 3A (CYP3A) inhibitors (eg, ketoconazole, indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, telithromycin, itraconazole, and nefazodone). These medications are prohibited 14 days before Randomization through the duration of the trial.
* Other exclusion criteria per protocol.

Primary outcomes:
measure: Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Study Drug-Related TEAEs
timeFrame: Day 1 up to Day 115
measure: Percent Change From Baseline in Urine Albumin Creatinine Ratio (UACR) Over Weeks 8 and 12
timeFrame: Baseline; Week 8 to Week 12
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Chula Vista
country: United States
facility: California Institute of Renal Research
state: California
city: Fullerton
country: United States
facility: St. Joseph Heritage Healthcare (St. Jude Hospital DBA)
state: California
city: La Mesa
country: United States
facility: California Institute of Renal Research
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute, Inc.
state: California
city: Los Angeles
country: United States
facility: American Institute of Research
state: California
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: Northridge
country: United States
facility: California Medical Research Associates, Inc. (CMRA)
state: California
city: Riverside
country: United States
facility: Riverside Nephrology Physicians, Inc.
state: California
city: San Dimas
country: United States
facility: California Kidney Specialists
state: California
city: San Dimas
country: United States
facility: North American Research Institute
state: California
city: Santa Monica
country: United States
facility: UCLA
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
state: California
city: Denver
country: United States
facility: Creekside Endocrine Associates
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: The George Washington University Medical Faculty Associates
state: District of Columbia
city: Hialeah
country: United States
facility: AGA Clinical Trials
state: Florida
city: Miami Lakes
country: United States
facility: Sweet Hope Research Speciality, Inc.
state: Florida
city: Miami
country: United States
facility: Leon Medical Research Corp.
state: Florida
city: Miami
country: United States
facility: Elite Clinical Research
state: Florida
city: Miami
country: United States
facility: DL Research Solutions
state: Florida
city: Miami
country: United States
facility: Premier Research Associates, Inc.
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC, Inc.
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Clinical Research Nephrology
state: Georgia
city: Columbus
country: United States
facility: Columbus Regional Research Institute
state: Georgia
city: Lawrenceville
country: United States
facility: Gwinnett Biomedical Research
state: Georgia
city: Macon
country: United States
facility: East Coast Institute for Clinical Research
state: Georgia
city: Macon
country: United States
facility: East Coast Institute for Research
state: Georgia
city: Nampa
country: United States
facility: Saltzer Medical Group
state: Idaho
city: Chicago
country: United States
facility: Research by Design, LLC
state: Illinois
city: Franklin
country: United States
facility: American Health Network of Indiana
state: Indiana
city: Manhattan
country: United States
facility: My Kidney Center
state: Kansas
city: Lexington
country: United States
facility: Kentucky Diabetes Endocrinology Center
state: Kentucky
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Flint
country: United States
facility: Aa Mrc, Llc
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis Heart & Vascular, P.C.
state: Missouri
city: Linden
country: United States
facility: NJ Heart, P.A.
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College, Division of Community Endocrinology
state: New York
city: Greenville
country: United States
facility: Physicians East Endocrinology
state: North Carolina
city: Greer
country: United States
facility: Mountain View Clinical Research
state: South Carolina
city: Orangeburg
country: United States
facility: South Carolina Nephrology & Hypertension Center
state: South Carolina
city: Memphis
country: United States
facility: University of Tennessee Health Science Center at Memphis University Hospital
state: Tennessee
city: Beaumont
country: United States
facility: Pioneer Research Solutions
state: Texas
city: El Paso
country: United States
facility: Academy of Diabetes, Thyroid and Endocrine, P.A.
state: Texas
city: Fort Worth
country: United States
facility: The Medical Group of Texas
state: Texas
city: Fort Worth
country: United States
facility: Rockwood Medical Center
state: Texas
city: Houston
country: United States
facility: Endocrine IPS, PLLC
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Lampasas
country: United States
facility: FMC Science, LLC
state: Texas
city: San Antonio
country: United States
facility: Clinical Advancement Center PLLC
state: Texas
city: San Antonio
country: United States
facility: Briggs Clinical Research
state: Texas
city: Burke
country: United States
facility: Burke Internal Medicine and Research
state: Virginia
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Spokane
country: United States
facility: Northside Endocrinology
state: Washington
Study officials:
affiliation: Cyclerion Therapeutics, Inc.
name: John Hanrahan, MD MPH
role: STUDY_DIRECTOR
References:
citation: Hanrahan JP, de Boer IH, Bakris GL, Wilson PJ, Wakefield JD, Seferovic JP, Chickering JG, Chien YT, Carlson K, Cressman MD, Currie MG, Milne GT, Profy AT. Effects of the Soluble Guanylate Cyclase Stimulator Praliciguat in Diabetic Kidney Disease: A Randomized Placebo-Controlled Clinical Trial. Clin J Am Soc Nephrol. 2020 Dec 31;16(1):59-69. doi: 10.2215/CJN.08410520. Epub 2020 Dec 16.