Study to Evaluate Sex Differences in the Acute Effects of PL-3994 in Heart Failure Subjects

NCT04318145 | Terminated Phase 2 FDA Drug

• 1 other identifier: PL-3994-701
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

A Multi-Center, Unblinded, Single-Arm Study to Evaluate Sex Differences in the Acute Effects of PL-3994 on Myocardial cGMP Enhancement and Hemodynamics in Heart Failure with Preserved Ejection Fraction

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

Heart Failure, Ejection Fraction

Outcome Measures

Primary Outcomes (2)

• Part A: Dose Ascension

  Reaching the maximum tolderated dose (MTD) as defined by meeting stopping criteria.

  1 day

• Part B: Coronary Sinus Levels

  Coronary sinus levels of cGMP post PL-3994 infusion as compared to baseline.

  1 day

Secondary Outcomes (6)

• Part B: Blood pressure measured in mmHg

  1 day

• Part B: Heart rate measured in beats per minute

  1 day

• Part B: Right atrial pressure measured in mmHg

  1 day

• Part B: Pulmonary artery pressure measured in mmHg

  1 day

• Part B: Pulmonary capillary wedge pressure measured in mmHg

  1 day

Study Arms (2)

Part A: PL-3994 Dose Ascension

EXPERIMENTAL

Dose ascension: up to 15 subjects with HFpEF. N = 3 per dose level, up to 5 dose levels.

Drug: PL-3994 Aqueous Intravenous Solution Dose Ascention

Part B: PL-3994 Single Dose

EXPERIMENTAL

Up to 40 subjects with HFpEF (20 Females, 20 Males) will receive a single dose of PL-3994.

Drug: PL-3994 Aqueous Intravenous Solution Single Dose

Interventions

PL-3994 Aqueous Intravenous Solution Dose Ascention DRUG

Following appropriate dilution, PL-3994 will be injected intravenously by site personnel as a bolus dose followed by continuous infusion

Also known as: PL-3994

Part A: PL-3994 Dose Ascension

PL-3994 Aqueous Intravenous Solution Single Dose DRUG

Following appropriate dilution, PL-3994 will be injected intravenously by site personnel as a bolus dose followed by continuous infusion

Also known as: PL-3994

Part B: PL-3994 Single Dose

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has provided written informed consent.
• Pre- or post-menopausal female or male age \> 21 years
• LVEF ≥ 45% by echocardiography within prior 6 months
• Symptoms of HF requiring treatment with diuretics for ≥ 30 days prior to enrollment
• Current symptoms of HF (NYHA class II-IV) at time of enrollment
• \. The subject has clinical indication for right heart catheterization for evaluation of HFpEF
• Negative pregnancy test in a female of childbearing potential

You may not qualify if:

• Orthostatic hypotension, systolic blood pressure \<100 mm Hg, diastolic blood pressure \< 50 mmHg.
• Any prior echocardiogram with LVEF \< 40%
• Hemoglobin \< 9 g/dl
• eGFR \< 30 mL/min/1.73 m2
• Hemodynamically significant arrhythmias within prior 4 weeks
• Acute coronary syndrome, cardiac surgery, or percutaneous coronary intervention within prior 3 months
• Any of the following cardiac diagnoses: active myocarditis, hypertrophic cardiomyopathy, \> moderate regurgitant valvular disease, any valvular stenosis, restrictive cardiomyopathy (including amyloid, sarcoid, or hemochromatosis), constrictive pericarditis, complex congenital heart disease, or pulmonary arterial hypertension
• Current need for IV inotropic medication
• Currently taking nitrates or having stopped nitrates within 24 hours of visit
• Currently taking antihistamines, antipsychotics, tri-cyclic antidepressants, catecholamines/related compounds, monoamine oxidase inhibitors, stimulants (including caffeine and nicotine), sympathomimetics, dopamine agonists. Additionally, medications that inhibit PDE activity will be prohibited during the study and for 5 half- lives prior to Day 1 so that cGMP measurements will not be affected
• Currently hospitalized for HF
• Any prior need for mechanical circulatory support
• Previous adverse reaction to the study drug
• Inability to comply with planned study procedures
• Pregnant or nursing mothers

Sponsors & Collaborators

• Palatin Technologies, Inc: lead

Study Sites (1)

Northwestern University

Evanston, Illinois, 60208, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

PL-3994

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Sangiv J. Shah, MD

  Northwestern University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: Single dose per subject, dose level ascension every 3 subjects. 5 dose levels are planned. An intermediate dose between planned doses may be chosen by the Sponsor/Investigator upon discussion after MTD is reached. Part B: Single dose, dose chosen from Part A.

Study Record Dates

• First Submitted: March 16, 2020
• First Posted: March 23, 2020
• Study Start: November 12, 2020
• Primary Completion: December 8, 2023
• Study Completion: December 8, 2023
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)