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

Heart Failure With Preserved Ejection Fraction Clinical Trial

— CAPACITY-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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03254485
• Other study ID #: C1973-204
• Status: Completed
• Phase: Phase 2
• Start date: November 7, 2017
• Est. completion date: August 19, 2019

Study information

• Verified date: August 2022
• Source: Akebia Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: August 19, 2019
• Est. primary completion date: August 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

Drug:
• IW-1973
Oral Tablet
• Placebo Oral Tablet
Oral Tablet

Locations

Country	Name	City	State
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	London Health Sciences Centre	London	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie De Quebec	Québec
Canada	CIUSSS de l'Estrie - CHUS	Sherbrooke	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
United States	Lousiana Heart Center	Bogalusa	Louisiana
United States	St. Luke's Regional Medical Center	Boise	Idaho
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Lahey Clinic	Burlington	Massachusetts
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Northwestern University	Chicago	Illinois
United States	Ohio State University Medical Center (OSUMC)	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	North Dallas Research Associates	Dallas	Texas
United States	Southwest Family Medicine Associates	Dallas	Texas
United States	Texas Health Research and Education Insitute	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Aurora Denver Cardiology	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	New Generation of Medical Research	Hialeah	Florida
United States	Franciscan Physician Network - Indiana Heart Physicians	Indianapolis	Indiana
United States	East Coast Institute for Research	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	JEHM	La Mesa	California
United States	Research Institute of Lancaster General Health	Lancaster	Pennsylvania
United States	Cardiology and Medicine Clinic	Little Rock	Arkansas
United States	South Denver Cardiology Associates	Littleton	Colorado
United States	Axis Clinical Trials	Los Angeles	California
United States	Unity Point Health	Madison	Wisconsin
United States	University of Wisconsin - Madison	Madison	Wisconsin
United States	PCRS Network, LLC	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	JEHM	National City	California
United States	Mount Sinai School of Medicine	New York	New York
United States	Valley Clinical Trials	Northridge	California
United States	Newton Clinical Research	Oklahoma City	Oklahoma
United States	South Oklahoma Heart Research	Oklahoma City	Oklahoma
United States	Stanford University	Palo Alto	California
United States	Broward Research Center	Pembroke Pines	Florida
United States	Unity Point Health - Methodist Hospital	Peoria	Illinois
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Arizona Arrhythmia Research Center	Phoenix	Arizona
United States	Progressive Medical Research	Port Orange	Florida
United States	Oregon Health & Science University (OHSU)	Portland	Oregon
United States	Virginia Commonwealth University Medical College of Virginia	Richmond	Virginia
United States	The Valley Hospital	Ridgewood	New Jersey
United States	Mayo Clinic	Rochester	Minnesota
United States	VA Healthcare John Cochran Medical Center	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	Schnitzler Cardiovascular Consultants	San Antonio	Texas
United States	Mayo Clinic	Scottsdale	Arizona
United States	PeaceHealth, Sacred Heart Physicians	Springfield	Oregon
United States	Madigan Army Medical Center	Tacoma	Washington
United States	ProMedica Toledo Hospital	Toledo	Ohio
United States	Harbor UCLA Medical Center	Torrance	California
United States	University of Arizona	Tucson	Arizona
United States	Oklahoma Heart Institute	Tulsa	Oklahoma
United States	Michigan Heart	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Akebia Therapeutics	Cyclerion Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Change From Baseline in 6-minute Walk Test (6MWT) Distance at Week 12	6MWT was a simple assessment of everyday functional capacity and provided a global evaluation of the organ/physiologic systems involved in exercise. 6MWT assessed the distance travelled in 6 minutes, measured at approximately the same time of day. 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 ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and Baseline value as a covariate.	Baseline and Week 12
Secondary	Change From Baseline in Ventilatory Efficiency at Week 12	Ventilatory efficiency was defined as minute ventilation/carbon dioxide (VE/VCO2) slope, production and was obtained from CPET. 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 ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and baseline value as a covariate.	Baseline and Week 12
Secondary	CPET Responders at Week 12	CPET responders were defined as participants who improved by at least 1.5 mL O2/kg/min in peak VO2 from Baseline to Week 12. Baseline is defined as the last non-missing measurement prior to the first dose of study drug.	At Week 12