Clinical trial NCT03254485: A Study of the Effect of IW-1973 on the Exercise Capacity of Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Safety and Efficacy of Different Doses of IW-1973 Over 12 Weeks in Patients With Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure With Preserved Ejection Fraction
Keywords: Heart Failure
Cardiovascular
HF
HFpEF
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Cyclerion Therapeutics
First posted: 2017-08-18
Enrollment: 196
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the CAPACITY-HFpEF study is to evaluate the safety and efficacy of IW-1973 compared with placebo when administered daily for approximately 12 weeks to patients with HFpEF. The study will evaluate the effect of oral IW-1973 on peak exercise capacity in patients with HFpEF, with or without permanent or persistent atrial fibrillation.


Eligibility criteria: Inclusion Criteria:

1. Patient is an ambulatory male or female ≥45 years old at the Screening Visit
2. Patient has heart failure with ejection fraction (EF) of ≥40%
3. Patient has a peak VO2 measuring \<80% of age- and sex-adjusted normal values
4. Patient has evidence in medical history supporting clinical heart failure syndrome consisting of at least 1 of the following:

   1. Hospitalization or emergency department visit for heart failure within the past year
   2. Elevated B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) within the past 6 months
   3. Echocardiographic evidence within the past 12 months of at least 2 of the following: left ventricular (LV) hypertrophy, left atrial (LA) enlargement, or diastolic dysfunction
   4. Hemodynamic evidence of elevated filling pressures
5. Patient meets at least 2 of the following criteria at the Screening Visit:

   1. Diagnosis of type 2 diabetes mellitus or prediabetes
   2. History of hypertension
   3. Body mass index (BMI) \>30 kg/m2
   4. Age ≥70 years

Exclusion Criteria:

1. Patient has had acute coronary syndrome or percutaneous coronary intervention within 30 days before Randomization
2. Patient has had cardiac transplantation or has cardiac transplantation planned during the study
3. Patient has had cardiac artery bypass graft, cardiac mechanical support implantation, or other cardiac surgery in the 3 months before the Screening Visit or planned during the study
4. Patient has severe chronic obstructive coronary disease as defined by chronic oxygen dependence
5. Patient had had heart failure hospitalization with discharge within 30 days before the Screening Visit
6. Patient has a history of clinically significant hypersensitivity or allergies to any of the inactive ingredients contained in the active or placebo drug products
7. 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
8. Patient is taking specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific inhibitors of PDE5, any supplements for the treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide (NO) donors in any form
9. Patient is taking strong cytochrome P450 3A (CYP3A) inhibitors
10. 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
11. 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
12. Other exclusion criteria per protocol

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Study Drug-related TEAEs
timeFrame: Day 1 up to Day 113
measure: Change From Baseline in Peak Oxygen Consumption (VO2) at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline in 6-minute Walk Test (6MWT) Distance at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Ventilatory Efficiency at Week 12
timeFrame: Baseline and Week 12
measure: CPET Responders at Week 12
timeFrame: At Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Arrhythmia Research Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Little Rock
country: United States
facility: Cardiology and Medicine Clinic
state: Arkansas
city: La Mesa
country: United States
facility: JEHM
state: California
city: Los Angeles
country: United States
facility: Axis Clinical Trials
state: California
city: National City
country: United States
facility: JEHM
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Torrance
country: United States
facility: Harbor UCLA Medical Center
state: California
city: Denver
country: United States
facility: Aurora Denver Cardiology
state: Colorado
city: Littleton
country: United States
facility: South Denver Cardiology Associates
state: Colorado
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Hialeah
country: United States
facility: New Generation of Medical Research
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute for Research
state: Florida
city: Miami
country: United States
facility: PCRS Network, LLC
state: Florida
city: Pembroke Pines
country: United States
facility: Broward Research Center
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Boise
country: United States
facility: St. Luke's Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Peoria
country: United States
facility: Unity Point Health - Methodist Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan Physician Network - Indiana Heart Physicians
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Bogalusa
country: United States
facility: Lousiana Heart Center
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Ypsilanti
country: United States
facility: Michigan Heart
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: VA Healthcare John Cochran Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center (OSUMC)
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: South Oklahoma Heart Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Newton Clinical Research
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Springfield
country: United States
facility: PeaceHealth, Sacred Heart Physicians
state: Oregon
city: Lancaster
country: United States
facility: Research Institute of Lancaster General Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: North Dallas Research Associates
state: Texas
city: Dallas
country: United States
facility: Texas Health Research and Education Insitute
state: Texas
city: Dallas
country: United States
facility: Southwest Family Medicine Associates
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Schnitzler Cardiovascular Consultants
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical College of Virginia
state: Virginia
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Madison
country: United States
facility: Unity Point Health
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie - CHUS
state: Quebec
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie De Quebec
Study officials:
affiliation: Cyclerion Therapeutics, Inc.
name: Jelena Seferovic, MD PhD
role: STUDY_DIRECTOR
References:
citation: Udelson JE, Lewis GD, Shah SJ, Zile MR, Redfield MM, Burnett J Jr, Parker J, Seferovic JP, Wilson P, Mittleman RS, Profy AT, Konstam MA. Effect of Praliciguat on Peak Rate of Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: The CAPACITY HFpEF Randomized Clinical Trial. JAMA. 2020 Oct 20;324(15):1522-1531. doi: 10.1001/jama.2020.16641.
citation: Udelson JE, Lewis GD, Shah SJ, Zile MR, Redfield MM, Burnett J Jr, Mittleman RS, Profy AT, Seferovic JP, Reasner D, Konstam MA. Rationale and design for a multicenter, randomized, double-blind, placebo-controlled, phase 2 study evaluating the safety and efficacy of the soluble guanylate cyclase stimulator praliciguat over 12 weeks in patients with heart failure with preserved ejection fraction (CAPACITY HFpEF). Am Heart J. 2020 Apr;222:183-190. doi: 10.1016/j.ahj.2020.01.009. Epub 2020 Jan 21.