A Study of the Effect of IW-1973 on the Exercise Capacity of Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)

NCT03254485 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: C1973-204
• Study Type: interventional
• Target: 196
• Locations: 2 countries
• Sites: 62

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.

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

Heart Failure; Cardiovascular; HF; HFpEF

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Study Drug-related TEAEs

  An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those adverse events (AEs) that started or worsened in severity after the administration of study drug. Causality relationship to study drug was per Investigator assessment. Number of participants with TEAEs and study drug-related TEAEs is presented.

  Day 1 up to Day 113

• Change From Baseline in Peak Oxygen Consumption (VO2) at Week 12

  Peak VO2 was obtained from Cardiopulmonary Exercise Test (CPET), which was used to evaluate the effect of praliciguat on peak exercise capacity. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an analysis of covariance (ANCOVA) model with treatment group and atrial fibrillation stratification factors as categorical variable terms and Baseline peak VO2 value as a covariate. Milliliter O2 per kilogram per minute = mL O2/kg/min

  Baseline and Week 12

Secondary Outcomes (3)

• Change From Baseline in 6-minute Walk Test (6MWT) Distance at Week 12

  Baseline and Week 12

• Change From Baseline in Ventilatory Efficiency at Week 12

  Baseline and Week 12

• CPET Responders at Week 12

  At Week 12

Study Arms (2)

IW-1973 High Dose

EXPERIMENTAL

Drug: IW-1973

Placebo

PLACEBO COMPARATOR

Placebo to match experimental drug

Drug: Placebo Oral Tablet

Interventions

IW-1973 DRUG

Oral Tablet

IW-1973 High Dose

Placebo Oral Tablet DRUG

Oral Tablet

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is an ambulatory male or female ≥45 years old at the Screening Visit
• Patient has heart failure with ejection fraction (EF) of ≥40%
• Patient has a peak VO2 measuring \<80% of age- and sex-adjusted normal values
• Patient has evidence in medical history supporting clinical heart failure syndrome consisting of at least 1 of the following:
• Hospitalization or emergency department visit for heart failure within the past year
• Elevated B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) within the past 6 months
• 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
• Hemodynamic evidence of elevated filling pressures
• Patient meets at least 2 of the following criteria at the Screening Visit:
• Diagnosis of type 2 diabetes mellitus or prediabetes
• History of hypertension
• Body mass index (BMI) \>30 kg/m2
• Age ≥70 years

You may not qualify if:

• Patient has had acute coronary syndrome or percutaneous coronary intervention within 30 days before Randomization
• Patient has had cardiac transplantation or has cardiac transplantation planned during the study
• 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
• Patient has severe chronic obstructive coronary disease as defined by chronic oxygen dependence
• Patient had had heart failure hospitalization with discharge within 30 days before the Screening Visit
• 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, any supplements for the treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide (NO) donors in any form
• Patient is taking strong cytochrome P450 3A (CYP3A) inhibitors
• 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

Sponsors & Collaborators

• Akebia Therapeutics: lead
• Cyclerion Therapeutics: collaborator

Study Sites (62)

Arizona Arrhythmia Research Center

Phoenix, Arizona, 85016, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

Cardiology and Medicine Clinic

Little Rock, Arkansas, 72204, United States

Location

JEHM

La Mesa, California, 91941, United States

Location

Axis Clinical Trials

Los Angeles, California, 90036, United States

Location

JEHM

National City, California, 91950, United States

Location

Valley Clinical Trials

Northridge, California, 91325, United States

Location

Stanford University

Palo Alto, California, 94305, United States

Location

Harbor UCLA Medical Center

Torrance, California, 90509, United States

Location

Aurora Denver Cardiology

Denver, Colorado, 80218, United States

Location

South Denver Cardiology Associates

Littleton, Colorado, 80120, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

New Generation of Medical Research

Hialeah, Florida, 33016, United States

Location

East Coast Institute for Research

Jacksonville, Florida, 32216, United States

Location

PCRS Network, LLC

Miami, Florida, 33126, United States

Location

Broward Research Center

Pembroke Pines, Florida, 33024, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

St. Luke's Regional Medical Center

Boise, Idaho, 83712, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Unity Point Health - Methodist Hospital

Peoria, Illinois, 61602, United States

Location

Franciscan Physician Network - Indiana Heart Physicians

Indianapolis, Indiana, 46237, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Lousiana Heart Center

Bogalusa, Louisiana, 70427, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Lahey Clinic

Burlington, Massachusetts, 01805, United States

Location

Michigan Heart

Ypsilanti, Michigan, 48197, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

VA Healthcare John Cochran Medical Center

St Louis, Missouri, 63106, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

The Valley Hospital

Ridgewood, New Jersey, 07450, United States

Location

Mount Sinai School of Medicine

New York, New York, 10025, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University Medical Center (OSUMC)

Columbus, Ohio, 43210, United States

Location

ProMedica Toledo Hospital

Toledo, Ohio, 43606, United States

Location

South Oklahoma Heart Research

Oklahoma City, Oklahoma, 73135, United States

Location

Newton Clinical Research

Oklahoma City, Oklahoma, 73159, United States

Location

Oklahoma Heart Institute

Tulsa, Oklahoma, 74104, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

PeaceHealth, Sacred Heart Physicians

Springfield, Oregon, 97477, United States

Location

Research Institute of Lancaster General Health

Lancaster, Pennsylvania, 17602, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

North Dallas Research Associates

Dallas, Texas, 75069, United States

Location

Texas Health Research and Education Insitute

Dallas, Texas, 75231, United States

Location

Southwest Family Medicine Associates

Dallas, Texas, 75235, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Schnitzler Cardiovascular Consultants

San Antonio, Texas, 78229, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Virginia Commonwealth University Medical College of Virginia

Richmond, Virginia, 23298, United States

Location

Madigan Army Medical Center

Tacoma, Washington, 98431, United States

Location

Unity Point Health

Madison, Wisconsin, 53713, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53792, United States

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Ecogene-21

Chicoutimi, Quebec, G7H 7K9, Canada

Location

CIUSSS de l'Estrie - CHUS

Sherbrooke, Quebec, J1G 2E8, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie De Quebec

Québec, G1V 4G5, Canada

Location

Related Publications (2)

• 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.

  PMID: 33079154 DERIVED

• 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.

  PMID: 32105984 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

praliciguat

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

Due to changes in study objectives and design (protocol amendment 3), all efficacy analyses was performed using only the praliciguat 40 mg and placebo groups; the praliciguat 10 mg and 20 mg groups were excluded from all efficacy analysis. For completeness, participants treated with both 10 mg and 20 mg praliciguat are included in the AE summaries for safety analyses, as well as for Participant Flow and Baseline Characteristics.

Results Point of Contact

• Title: Akebia Therapeutics
• Organization: Akebia Therapeutics

trials@akebia.com

6178446128

Study Officials

• Jelena Seferovic, MD PhD

  Cyclerion Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 16, 2017
• First Posted: August 18, 2017
• Study Start: November 7, 2017
• Primary Completion: August 19, 2019
• Study Completion: August 19, 2019
• Last Updated: September 15, 2022
• Results First Posted: September 15, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (57); CA (5)