A Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of Intravenous APD418 in Adult Participants With Heart Failure With Reduced Ejection Fraction

NCT ID: NCT05139615

Last Updated: 2023-11-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-28
• Study Completion Date: 2022-09-19

Brief Summary

The purpose of this study is to evaluate the safety, pharmacokinetics, and effect on cardiac function of intravenous APD418 in adult participants with heart failure with reduced ejection fraction (HFrEF).

Detailed Description

This study has an adaptive design, in which dose escalation in Part A will inform dose expansion in Part B. Part A is a single-ascending dose, placebo-controlled study planned to consist of 5 cohorts evaluating 5 doses of APD418. Part B is a parallel-treatment group study planned to evaluate 2 doses of APD418 and placebo. Participants in Part A cannot participate in Part B.

Conditions

Acute Heart Failure With Reduced Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

APD418 (Part A: Dose Cohort 1-5)

Group Type: EXPERIMENTAL

APD418

Intervention Type: DRUG

Participants will receive a single dose of APD418 as an intravenous (IV) infusion.

APD418 (Part B: Dose Group 1 and 2)

Group Type: EXPERIMENTAL

APD418

Intervention Type: DRUG

Participants will receive a single dose of APD418 as an IV infusion.

Placebo (Part A: Cohort 1-5 and Part B)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive a single dose of APD418 matching placebo as an IV infusion.

Interventions

APD418

Participants will receive a single dose of APD418 as an intravenous (IV) infusion.

Intervention Type: DRUG

APD418

Participants will receive a single dose of APD418 as an IV infusion.

Intervention Type: DRUG

Placebo

Participants will receive a single dose of APD418 matching placebo as an IV infusion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Advanced chronic Heart Failure with Reduced Ejection Fraction (HFrEF), defined as left ventricular ejection fraction (LVEF) less than or equal to (≤) 35% at Screening, including documented history of HFrEF (LVEF ≤ 35%) for at least 4 months prior to Screening
• New York Heart Association Class II-IV
• Cardiac index ≤ 2.5 liters per minute per square meter (L/min/m^2) and pulmonary capillary wedge pressure ≥ 15 millimeters of mercury (mm Hg) at Day 1
• Body mass index 18.0 to 37.0 kilograms per square meter (kg/m^2), inclusive, and body weight < 150 kg at Screening and Day 1

Exclusion Criteria

• Hemodynamically unstable at Day 1 or in the opinion of the Investigator likely to progress to becoming hemodynamically unstable during the course of the study
• Treated with carvedilol or at a dose higher than a total of 25 milligrams per day any time within 72 hours of Day 1 through the end of the in-clinic observation Post-dose Period.
• Receiving any mechanical (respiratory or circulatory) or renal support therapy at Screening or Day 1
• Systolic Blood Pressure ≤ 90 millimeter of mercury (mm Hg) or ≥ 160 mm Hg, or Heart Rate < 50 beats per minute (bpm) or > 110 bpm, at Screening or Day 1
• Recently treated with inotropic, intravenous (IV) vasoactive or IV diuretic therapy, or expected to require such therapy with these drugs any time from Day 1 through the end of study conduct.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arena is a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

James A. Haley Veterans' Hospital

Tampa, Florida, United States

UnityPoint Health - Methodist Hospital

Peoria, Illinois, United States

UTHealth

Houston, Texas, United States

Health Science Center Utah

Salt Lake City, Utah, United States

University of Wisconsin

Madison, Wisconsin, United States

Immanuel Hospital Bernau Brandenburg Heart Center

Bernau bei Berlin, Brandenburg, Germany

Kerckhoff-Klinik Forschungsgesellschaft GmbH

Bad Nauheim, , Germany

Universitatsmedizin Greifwald

Greifswald, , Germany

Konstantinopouleio General Hospital of Nea Ionia - Patision ''Agia Olga''

Nea Ionia, Athens, Greece

Interbalkan European Medical Center

Pylaia, Thessaloniki, Greece

General University Hospital of Larissa

Larissa, , Greece

American Heart of Poland S.A.

Gniezno, , Poland

Krakowski Szpital Specjalistyczny im. Jana Pawla II

Krakow, , Poland

Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego

Wroclaw, , Poland

Clinical Hospital Centre Zemun

Belgrade, , Serbia

University Clinical Centre of Serbia

Belgrade, , Serbia

Institute for Cardiovascular Diseases Dedinje

Belgrade, , Serbia

Clinical Hospital Center Bezanijska Kosa

Belgrade, , Serbia

Institute for Cardiovascular Diseases of Vojvodina

Kamenitz, , Serbia

Clinical Center of Kragujevac

Kragujevac, , Serbia

Healthcare Center Uzice

Užice, , Serbia

Countries

United States; Germany; Greece; Poland; Serbia

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://pmiform.com/clinical-trial-info-request?StudyID=APD418-201

To obtain contact information for a study center near you, click here.

Other Identifiers

C5061001

Identifier Type: OTHER

Identifier Source: secondary_id

2020-006131-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APD418-201

Identifier Type: -

Identifier Source: org_study_id