HU6 for Heart Failure

(HFpEF Trial)

No longer recruiting at 14 trial locations

Overseen By Janice Durden

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2

Sponsor: Rivus Pharmaceuticals, Inc.

Must not be taking: GLP-1 antagonists, SGLT2 inhibitors

Disqualifiers: Malignancy, Bariatric surgery, Myocarditis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 134 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called HU6 for individuals with a specific type of heart failure known as HFpEF, who also have obesity. The goal is to determine the safety and tolerance of HU6 at various doses compared to a placebo (a non-active substance used for comparison). Participants will begin with lower doses and may increase to higher doses if deemed safe. The trial seeks individuals experiencing heart failure symptoms with a body mass index (BMI) of 30 or higher. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that participants have stable doses of their current medications for at least 30 days before screening, meaning no new medications or significant changes in dosage. If you are on diuretics, you must be on a stable regimen that allows for flexible dosing.

Is there any evidence suggesting that HU6 is likely to be safe for humans?

Research has shown that HU6 has been well-tolerated in past studies. In trials involving individuals with non-alcoholic fatty liver disease and a high BMI, HU6 did not raise major safety concerns compared to a placebo. Another study found HU6 generally safe, with no serious side effects reported. This suggests HU6 is relatively safe for humans, though all treatments can have some side effects. Participants in earlier studies managed well with HU6, but ongoing research will continue to monitor its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for heart failure with preserved ejection fraction (HFpEF), which typically focus on diuretics, blood pressure medications, and lifestyle changes, HU6 offers a novel approach. HU6 is unique because it targets metabolic processes, potentially improving energy use in obese patients with HFpEF. Researchers are excited about HU6 because it could provide a new way to address the metabolic challenges associated with obesity in HFpEF, which current treatments don't specifically target. This new mechanism of action could lead to better outcomes for patients who haven't found relief with existing therapies.

What evidence suggests that HU6 could be an effective treatment?

Research has shown that HU6, which participants in this trial may receive, can help reduce body weight and fat. Studies found that HU6 led to significant decreases in body fat, including belly fat, while preserving muscle mass. HU6 speeds up metabolism, enabling the body to burn fat more efficiently. People with non-alcoholic fatty liver disease (NAFLD) and high BMI experienced improvements when using HU6. This evidence suggests HU6 could be promising for those dealing with obesity and related conditions. ^{1 3 6 7 8}

Who Is on the Research Team?

Shaharyar Khan, PhD

Principal Investigator

Rivus Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

Inclusion Criteria

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.

You have to meet at least one of the following criteria for heart failure:

Exclusion Criteria

You have a currently active autoimmune disease affecting your connective tissues.

You have a specific type of heart condition called primary cardiomyopathy as determined by the doctor.

You have a current case of heart inflammation, either caused by COVID or another reason.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

40 days

1-2 visits (in-person)

Treatment

Participants receive HU6 or placebo in a dose escalation manner: 150 mg daily for 20 days, followed by 300 mg daily for 20 days, and 450 mg daily for 94 days if safety and tolerability are demonstrated.

134 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• HU6
• Placebo

How Is the Trial Designed?

Group I: Active Treatment: HU6 Planned doses of HU6; N = 31 Experimental Treatment 1 Intervention

Group II: Placebo Comparator Non-active study drug N = 31 Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Rivus Pharmaceuticals, Inc.

Lead Sponsor

Trials

9

Recruited

540+

Published Research Related to This Trial

The study systematically analyzed placebo effects from randomized, placebo-controlled trials, revealing that while placebos can influence clinical symptoms, they do not affect laboratory values like blood glucose in diabetics.

Placebo side effects were found to be similar to those of active treatments, highlighting the importance of careful placebo use in clinical research to ensure patient safety and informed consent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. Weihrauch, TR.[2019]

In a review of 113 placebo-controlled randomized clinical trials published in 2016, only 19.5% of journal articles and 45.1% of study protocols provided descriptions of placebo contents, highlighting a significant lack of transparency in clinical trial reporting.

None of the journal publications explained the rationale for the choice of placebo ingredients, which raises concerns about the potential effects of active placebos on trial outcomes and complicates the assessment of the safety and efficacy of experimental interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definition and rationale for placebo composition: Cross-sectional analysis of randomized trials and protocols published in high-impact medical journals. Hong, K., Rowhani-Farid, A., Doshi, P.[2023]

A new checklist called TIDieR-Placebo has been developed to improve the reporting of placebo or sham interventions in clinical trials, ensuring that researchers clearly describe these components alongside active treatments.

The checklist was created through expert consultation and aims to enhance the transparency of trial results, which is crucial for accurately assessing the benefits and harms of active interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. Howick, J., Webster, RK., Rees, JL., et al.[2020]

A review of 192 randomized clinical trials revealed that safety information is often underreported, with only 46% specifying reasons for withdrawals due to toxicity and only 39% adequately reporting clinical adverse effects.

To enhance safety reporting, the study emphasizes the need for standardized scales for adverse effects, systematic data collection, and detailed reporting of severe reactions, suggesting that improved practices could lead to better safety insights in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving safety reporting from randomised trials. Ioannidis, JP., Lau, J.[2018]

In a randomized, double-blind clinical trial involving 125 patients with referred shoulder pain, applying a force to the C5 vertebra using a mechanically assisted instrument (MAI) significantly improved internal rotation strength after 6 months (P = 0.04).

While the treatment cohort experienced a reduction in the frequency of extreme shoulder pain (from weekly to monthly), there was no significant change in the severity of pain or other functional outcomes compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Assessing the Effects of Applying a Force to C5 by a Mechanically Assisted Instrument on Referred Pain to the Shoulder. Hardas, GM., Murrell, GAC.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37806314/

Safety and efficacy of once-daily HU6 versus placebo in ... We aimed to assess the safety and efficacy of HU6 compared with placebo in people with non-alcoholic fatty liver disease (NAFLD) and high BMI.

2. prnewswire.com prnewswire.com/news-releases/rivus-pharmaceuticals-announces-positive-topline-results-from-phase-2-m-accel-trial-of-hu6-showing-significant-reductions-in-liver-fat-in-patients-with-mash-302488778.html

Rivus Pharmaceuticals Announces Positive Topline ... Treatment with HU6 significantly reduced body weight, body fat and abdominal visceral fat with preservation of skeletal muscle mass versus placebo and was well ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04874233

Phase 2a Study of HU6 in Subjects With Elevated Liver Fat ... A 61-day randomized, double blind, placebo-controlled trial to assess the safety and efficacy of three doses of HU6 in subjects with elevated liver fat and ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40072462/

The HuMAIN-HFpEF Randomized Clinical Trial HU6 is a novel, controlled metabolic accelerator that enhances mitochondrial uncoupling resulting in increased metabolism and fat-specific weight loss.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S246812532300198X

Safety and efficacy of once-daily HU6 versus placebo in ... We aimed to assess the safety and efficacy of HU6 compared with placebo in people with non-alcoholic fatty liver disease (NAFLD) and high BMI.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07170189

Phase 1, Open-Label, Randomized, Study of the Safety ... This is a five-part study being conducted to evaluate the safety, tolerability and pharmacokinetics of the HU6 tablet and capsule formulations ...

7. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253(23)00198-X/abstract

Safety and efficacy of once-daily HU6 versus placebo in ... We aimed to assess the safety and efficacy of HU6 compared with placebo in people with non-alcoholic fatty liver disease (NAFLD) and high BMI.

8. prnewswire.com prnewswire.com/news-releases/rivus-pharmaceuticals-to-present-clinical-data-from-phase-2a-m-accel-trial-of-hu6-in-mash-as-late-breaker-oral-presentation-at-aasld-the-liver-meeting-2025-302582497.html

Rivus Pharmaceuticals to Present Clinical Data from ... Rivus' lead CMA HU6 (ANT-channel activator) has demonstrated positive results and a well-tolerated safety profile in across 3 Phase 2 clinical ...