Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF

NCT05284617 | Completed Phase 2 FDA Drug

• 1 other identifier: RIV-HU6-2201
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 15

Brief Summary

This is a Phase 2A, randomized, parallel-group, placebo-controlled, double-blind, within subject dose escalation trial with 3 dose levels of HU6 and placebo. Subjects will be randomized (1:1) either to HU6 or placebo. Two dose levels will be administered in sequential order (150 mg daily followed by 300 mg daily), each for 20 days, to reach the third and highest dose of 450 mg daily if safety and tolerability are demonstrated at the lower 2 preceding doses. Administration of the 450 mg high dose will continue for a total of 94 days, with a safety follow-up visit within \~14 days of the last dose.

Conditions

Heart Failure With Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Evaluate weight reduction while on HU6 treatment

  Assess the rate and amount of body weight loss over the course of HU6 treatment

  5 months

Study Arms (2)

Active Treatment: HU6 Planned doses of HU6; N = 31

EXPERIMENTAL

Drug: HU6

Placebo Comparator Non-active study drug N = 31

PLACEBO COMPARATOR

Drug: Placebo

Interventions

HU6 DRUG

HU6 is being evaluated for its efficacy in improving cardiovascular function in obese subjects with HF with preserved ejection fraction (HFpEF).

Active Treatment: HU6 Planned doses of HU6; N = 31

Placebo DRUG

Placebo

Placebo Comparator Non-active study drug N = 31

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male or female, ≥40 years of age.
• Competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) and must sign the form prior to the initiation of any study procedures.
• Body mass index (BMI) ≥30 kg/m2;
• Signs and symptoms of HF in the judgement of the Investigator, and meets the following disease severity criteria:
• a. KCCQ OSS ≤80; b. NYHA Classification Class II-III; c. Baseline peak VO2 ≤18 mL/kg/min for females or ≤20 mL/kg/min for males; d. Respiratory exchange ratio (respiratory quotient) (RER \[RQ\]) at baseline of \>1.0; e. Left ventricular ejection fraction (EF) ≥50%; f. At least 1 of the following objective criteria for HF: i. Documented hospitalization with HF as primary cause within in last year, or if greater than the past year, then with addition of structural heart disease on echocardiography (increased left atrial volume size or left ventricular hypertrophy, with sex-specific cut-points as per Lang, 2015) as follows:
• Left ventricular hypertrophy (LVH):
• Men: Either septal wall thickness (cm) either ≥1.1 or posterior wall thickness ≥1.1;
• Women: Either septal wall thickness (cm) either ≥ 1.0 or posterior wall thickness ≥1.0;
• Left atrial dilation (LAD): AP dimension (cm): ≥4.0 in men; \>3.8 in women; ii. Pulmonary capillary wedge pressure (PCWP) at rest \>15 mmHg (or left ventricular end-diastolic pressure \[LVEDP\] ≥18 mmHg) or \>25 mmHg (or 2.0 mmHg/L/min) with exercise in the last year; iii. E/e' ratio ≥14 at septal annulus at rest on Doppler and tissue Doppler imaging in the last year; or iv. Currently elevated NT-proBNP defined as \>125 pg/mL without atrial fibrillation and \>350 pg/mL for subjects with chronic controlled atrial fibrillation.
• Participants should maintain their stable level of physical activity throughout the duration of the study and must agree to not enroll in an exercise training program during the study.
• Participants should maintain their stable diet and no plan to enter into a weight loss program prior to or during the course of the study.
• Euthyroid as assessed by a thyroid profile utilizing thyroid stimulating hormone (TSH) and free thyroxine (T4) testing at screening. Subjects with a stable history of thyroid disease and who have been on stable doses of thyroid medications for a minimum of 4 months can be enrolled.
• Ambulatory (not wheelchair- or scooter-dependent) and able to perform upright exercise testing including a 6 MWT.
• Stable doses of medications (defined as no new medication or change in existing dose of medication ≥50%) for 30 days prior to screening, with additional specific criteria for the diuretics:
• If treated with a loop or thiazide diuretic, must be on stable regimen, which dose permits a flexible diuretic dosing schedule.

You may not qualify if:

• Life expectancy \<1 year due to non-cardiovascular reasons, in the judgement of the Investigator.
• History of malignancy within 5 years (except non-high-grade skin cancers, carcinoma-in-situ, or low-grade prostate cancer).
• Weight change (gain or loss) of ≥10 pounds either by self-reporting or documented weight loss within the past 90 days.
• Bariatric surgery prior to screening or planned bariatric surgery during the course of the study.
• Treatment with GLP-1 receptor antagonist begun within 1 year of screening.
• Treatment with SGLT2 inhibitors begun within 6 months of screening.
• Intolerance to MRI or with conditions contraindicated for MRI procedures including but not limited to:
• Having surgical clips/metallic implants/shrapnel/internal electric implants; or
• Inability to fit into MRI scanner due to subject habitus or exceeding weight tolerance limit of the scanner (generally, 350 or 400 lbs, dependent on manufacturer); or
• Claustrophobia: history of severe claustrophobia that would lead to inability to conduct MRI.
• Current acute decompensated HF requiring intravenous (IV) diuretics or recent (\<1 month before screening) hospitalization for HF.
• Primary cardiomyopathy (e.g., constrictive, restrictive, infiltrative, toxic, hypertrophic \[congenital\], congenital, or any other primary cardiomyopathy, in the judgement of the Investigator.
• Active myocarditis (COVID-induced or otherwise).
• Active collagen vascular disease.
• Current greater than moderate left- or right sided valve disease, in the opinion of the Investigator.

Sponsors & Collaborators

• Rivus Pharmaceuticals, Inc.: lead

Study Sites (15)

National Heart Institute

Beverly Hills, California, 90211, United States

Location

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center

Torrance, California, 90502, United States

Location

New Generation of Medical Research

Hialeah, Florida, 33002, United States

Location

Broward Research Center

Pembroke Pines, Florida, 33029, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Luke's Mid America Heart Institute

Kansas City, Missouri, 64111, United States

Location

Weill Cornell Medicine

New York, New York, 10012, United States

Location

Wake Forest

Winston-Salem, North Carolina, 27105, United States

Location

The Lindner Center for Research and Education at The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• Pandey A, Lewis GD, Borlaug BA, Shah SJ, Sauer AJ, Litwin S, Sharma K, Jorkasky DK, Tarka EA, Khan SM, Kitzman DW. Novel Controlled Metabolic Accelerator for Obesity-Related HFpEF: The HuMAIN-HFpEF Randomized Clinical Trial. JAMA Cardiol. 2025 Jun 1;10(6):609-616. doi: 10.1001/jamacardio.2025.0103.

  PMID: 40072462 DERIVED

Study Officials

• Shaharyar Khan, PhD

  Rivus Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

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

Model Details: This is a Phase 2A, randomized, parallel-group, placebo-controlled, double-blind, within subject dose escalation trial with 3 dose levels of HU6 and placebo. Subjects will be randomized (1:1) either to HU6 or placebo.

Study Record Dates

• First Submitted: March 9, 2022
• First Posted: March 17, 2022
• Study Start: October 30, 2022
• Primary Completion: May 24, 2024
• Study Completion: May 30, 2024
• Last Updated: August 26, 2024

Record last verified: 2024-08

Locations

US (15)