A Trial to Study Neladenoson Bialanate Over 20 Weeks in Patients With Chronic Heart Failure With Reduced Ejection Fraction (PANTHEON)

• ClinicalTrials.gov Identifier: NCT02992288
• Recruitment Status: Completed
• First Posted: December 14, 2016
• Results First Posted: April 23, 2019
• Last Update Posted: April 23, 2019
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: December 12, 2016
• First Posted Date: December 14, 2016
• Results First Submitted Date: March 11, 2019
• Results First Posted Date: April 23, 2019
• Last Update Posted Date: April 23, 2019
• Actual Study Start Date: February 22, 2017
• Actual Primary Completion Date: March 28, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 19, 2019)

• Absolute Change From Baseline in Left Ventricular Ejection Fraction (LVEF) (%) at Week 20 Measured by Echocardiography [ Time Frame: Baseline, Week 20 ]
  Left ventricular ejection fraction (LVEF) was measured by echocardiography. Mean and standard deviation were reported.
• Absolute Change From Baseline in Log-transformed NT-pro B-type Natriuretic Peptide (BNP) at Week 20 [ Time Frame: Baseline, Week 20 ]
  NT-pro b-type Natriuretic Peptide (BNP) was measured. Mean and standard deviation were reported.

Original Primary Outcome Measures (submitted: December 12, 2016)

• Absolute change from baseline in left ventricular ejection fraction (LVEF; %) after 20 weeks [ Time Frame: At 20 weeks of treatment ]
• Absolute change from baseline in log-transformed NT-proBNP (N-terminal pro-hormone b-type natriuretic peptide ) (pg/mL) after 20 weeks [ Time Frame: At 20 weeks of treatment ]

Current Secondary Outcome Measures (submitted: April 19, 2019)

• Change From Baseline in Left Ventricular End-Systolic Volume (LVESV) at Week 20 [ Time Frame: Baseline, Week 20 ]
  LVESV was defined as the volume of blood in the left ventricle at the end of contraction, or systole and the beginning of filling or diastole. Mean and standard deviation were reported.
• Change From Baseline in Left Ventricular End-Diastolic Volume (LVEDV) at Week 20 [ Time Frame: Baseline, Week 20 ]
  LVEDV was defined as the volume of blood in the left ventricle at end load or filling in diastole or the amount of blood in the ventricles just before systole. Mean and standard deviation were reported.
• Change From Baseline in High Sensitivity Troponin T (Hs-TNT) at Week 20 [ Time Frame: Baseline, Week 20 ]
  High sensitivity troponin T (hs-TNT) was measured. Mean and standard deviation were reported.
• Number of Participants With Composite Efficacy Outcome [ Time Frame: Baseline up to Week 26 ]
  Composite efficacy outcome was the first occurrence of CV death, HF hospitalization or urgent visit for HF. Number of participants with composite efficacy outcome were reported.
• Number of Participants With Cardiovascular (CV) Mortality [ Time Frame: Baseline up to Week 26 ]
  Cardiovascular (CV) mortality was assessed. Number of participants with CV mortality were reported.
• Number of Participants With Heart Failure (HF) Hospitalization and Urgent Visits for Heart Failure (HF) [ Time Frame: Baseline up to Week 26 ]
  Number of participants with HF hospitalization and urgent visits for HF were reported.

Original Secondary Outcome Measures (submitted: December 12, 2016)

• Left ventricular end-systolic volume (LVESV; mL) [ Time Frame: At 20 weeks of treatment ]
  Key echocardiographic parameter, measured values and absolute change from baseline at 20 weeks.
• Left ventricular end-diastolic volume (LVEDV; mL) [ Time Frame: At 20 weeks of treatment ]
  Key echocardiographic parameter, measured values and absolute change from baseline at 20 weeks.
• High sensitivity troponin T (hs-TNT; ng/L), measured values (log transformed) and absolute / relative change from baseline at 20 weeks as a biomarker of myocardial injury [ Time Frame: At 20 weeks of treatment ]
• Clinical outcomes [ Time Frame: At 20 weeks of treatment ]
  Clinical outcomes measured by cardiovascular (CV) mortality, heart failure (HF) hospitalization and urgent visits for HF.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial to Study Neladenoson Bialanate Over 20 Weeks in Patients With Chronic Heart Failure With Reduced Ejection Fraction
• Official Title: A Multicenter, Randomized, Placebo-controlled, Parallel Group, Double Blind, Dose-finding Phase II Trial to Study the Efficacy, Safety, Pharmacokinetic and Pharmacodynamic Effects of the Oral Partial Adenosine A1 Receptor Agonist Neladenoson Bialanate Over 20 Weeks in Patients With Chronic Heart Failure With Reduced Ejection Fraction
• Brief Summary: The objective of the study is to find the optimal dose of once daily oral neladenoson bialanate (BAY 1067197) when given in addition to standard therapy for heart failure with reduced ejection fraction (HFrEF).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Heart Failure

Intervention

• Drug: Neladenoson bialanate (BAY1067197)
  5 mg orally once daily for 20 weeks
• Drug: Neladenoson bialanate (BAY1067197)
  10 mg orally once daily for 20 weeks
• Drug: Neladenoson bialanate (BAY1067197)
  20 mg orally once daily for 20 weeks
• Drug: Neladenoson bialanate (BAY1067197)
  30 mg orally once daily for 20 weeks
• Drug: Neladenoson bialanate (BAY1067197)
  40 mg orally once daily for 20 weeks
• Drug: Placebo
  Orally once daily for 20 weeks

Study Arms

• Experimental: Neladenoson bialanate (BAY1067197) (5 mg)
  Chronic heart failure with reduced ejection fraction
  Intervention: Drug: Neladenoson bialanate (BAY1067197)
• Experimental: Neladenoson bialanate (BAY1067197) (10 mg)
  Chronic heart failure with reduced ejection fraction
  Intervention: Drug: Neladenoson bialanate (BAY1067197)
• Experimental: Neladenoson bialanate (BAY1067197) (20 mg)
  Chronic heart failure with reduced ejection fraction
  Intervention: Drug: Neladenoson bialanate (BAY1067197)
• Experimental: Neladenoson bialanate (BAY1067197) (30 mg)
  Chronic heart failure with reduced ejection fraction
  Intervention: Drug: Neladenoson bialanate (BAY1067197)
• Experimental: Neladenoson bialanate (BAY1067197) (40 mg)
  Chronic heart failure with reduced ejection fraction
  Intervention: Drug: Neladenoson bialanate (BAY1067197)
• Placebo Comparator: Placebo
  Chronic heart failure with reduced ejection fraction
  Intervention: Drug: Placebo

• Publications *: Voors AA, Bax JJ, Hernandez AF, Wirtz AB, Pap AF, Ferreira AC, Senni M, van der Laan M, Butler J; PANTHEON Investigators. Safety and efficacy of the partial adenosine A1 receptor agonist neladenoson bialanate in patients with chronic heart failure with reduced ejection fraction: a phase IIb, randomized, double-blind, placebo-controlled trial. Eur J Heart Fail. 2019 Nov;21(11):1426-1433. doi: 10.1002/ejhf.1591. Epub 2019 Sep 16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 30, 2017): 427
• Original Estimated Enrollment (submitted: December 12, 2016): 384
• Actual Study Completion Date: May 16, 2018
• Actual Primary Completion Date: March 28, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men or women aged 18 years and older
• Diagnosis of chronic heart failure (CHF), NYHA ( New York Heart Association ) class II-IV, LVEF ≤ 35% and elevated NT-proBNP

Exclusion Criteria:

• Acute de-novo heart failure
• Requirement of any intravenous (IV) treatments following 48 hours prior to randomization
• Mechanical support (e.g. intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device)
• Any cause of chronic heart failure other than ischemic cardiomyopathy and idiopathic dilated cardiomyopathy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy, Belgium, Bulgaria, Germany, Greece, Israel, Japan, Netherlands, Poland, Spain, United States

Administrative Information

• NCT Number: NCT02992288
• Other Study ID Numbers: 15128; 2016-003839-38 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Bayer
• Study Sponsor: Bayer
• Collaborators: Not Provided

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: April 2019