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

NCT05139615 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: APD418-201C50610012020-006131-10
• Study Type: interventional
• Target: 22
• Locations: 5 countries
• Sites: 21

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).

Conditions

Acute Heart Failure With Reduced Ejection Fraction

Keywords

Heart failure with reduced ejection fraction; HFrEF; APD418; Acute Heart Failure (AHF)

Outcome Measures

Primary Outcomes (1)

• Part A: Change in Cardiac Index (CI) Measured by Right Heart Catheterization (RHC) From Baseline to End of Intravenous (IV) Infusion at 6 Hours

  Cardiac index (CI) is a hemodynamic parameter that relates the cardiac output (CO) from left ventricle in one minute to body surface area (BSA), thus relating heart performance to the body size of the participant. It was measured by RHC.

  Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

Secondary Outcomes (29)

• Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours

  Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

• Part A: Change in Stroke Volume Index (SVI) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

  Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

• Part A: Change in Left Ventricular Ejection Fraction (LVEF) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

  Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

• Part A: Change in Fractional Shortening (FS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

  Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

• Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

  Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

Other Outcomes (3)

• Part A: Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)

  Anytime between 0 to 6 hours, 6 to 10 hours and 10 to 24 hours post infusion start

• Part A: Total Amount of Unchanged Drug Excreted in Urine Over the Collection Period (Amount Excreted [Ae])

  Pre-dose (0) to 24 hours post infusion start, collected over 0 to 6 hour, 6 to 10 hour and 10 to 24-hour intervals

• Part A: Fraction of Drug Excreted Unchanged (Fe) in Urine

  Pre-dose (0) to 24 hours post infusion start, collected over 0 to 6 hour, 6 to 10 hour and 10 to 24-hour intervals

Study Arms (3)

APD418 (Part A: Dose Cohort 1-5)

EXPERIMENTAL

Drug: APD418

APD418 (Part B: Dose Group 1 and 2)

EXPERIMENTAL

Drug: APD418

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

PLACEBO COMPARATOR

Drug: Placebo

Interventions

APD418 DRUG

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

APD418 (Part A: Dose Cohort 1-5)

Placebo DRUG

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

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

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead
• Arena is a wholly owned subsidiary of Pfizer: collaborator

Study Sites (21)

James A. Haley Veterans' Hospital

Tampa, Florida, 33612, United States

Location

UnityPoint Health - Methodist Hospital

Peoria, Illinois, 61606, United States

Location

UTHealth

Houston, Texas, 77030, United States

Location

Health Science Center Utah

Salt Lake City, Utah, 84132, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Immanuel Hospital Bernau Brandenburg Heart Center

Bernau bei Berlin, Brandenburg, 16321, Germany

Location

Kerckhoff-Klinik Forschungsgesellschaft GmbH

Bad Nauheim, 61231, Germany

Location

Universitatsmedizin Greifwald

Greifswald, 17475, Germany

Location

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

Nea Ionia, Athens, 14233, Greece

Location

Interbalkan European Medical Center

Pylaia, Thessaloniki, 55535, Greece

Location

General University Hospital of Larissa

Larissa, 41110, Greece

Location

American Heart of Poland S.A.

Gniezno, 62-200, Poland

Location

Krakowski Szpital Specjalistyczny im. Jana Pawla II

Krakow, 31-202, Poland

Location

Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego

Wroclaw, 50-556, Poland

Location

Clinical Hospital Centre Zemun

Belgrade, 11 070, Serbia

Location

University Clinical Centre of Serbia

Belgrade, 11000, Serbia

Location

Institute for Cardiovascular Diseases Dedinje

Belgrade, 11040, Serbia

Location

Clinical Hospital Center Bezanijska Kosa

Belgrade, 11080, Serbia

Location

Institute for Cardiovascular Diseases of Vojvodina

Kamenitz, 21204, Serbia

Location

Clinical Center of Kragujevac

Kragujevac, 34000, Serbia

Location

Healthcare Center Uzice

Užice, 31000, Serbia

Location

Related Links

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

Limitations and Caveats

This study was terminated early due to a business decision that was not due to any safety concerns. The number of participants was smaller than originally planned and only summary statistics were therefore generated for primary and secondary outcome measures.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 18, 2021
• First Posted: December 1, 2021
• Study Start: December 28, 2021
• Primary Completion: September 19, 2022
• Study Completion: September 19, 2022
• Last Updated: November 9, 2023
• Results First Posted: November 9, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share

Locations

DE (3); GR (3); SE (7); PL (3); US (5)