JK07 for Heart Failure

(RENEU-HF Trial)

Recruiting at 77 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Salubris Biotherapeutics Inc

Must be taking: Anticoagulants

Disqualifiers: Uncontrolled hypertension, Stroke, Syncope, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called JK07 in people aged 18-85 who have heart failure. The study includes two groups based on how well their heart is pumping. Participants will receive either a low dose or high dose of JK07. The goal is to see if JK07 can improve heart function and help these patients feel better.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it mentions that participants should have stable heart failure and be on optimal medical therapy. It's best to discuss your specific medications with the trial team.

What safety data exists for JK07 in humans?

Early clinical trials using IL-1 blockade, like anakinra, in heart failure patients have shown promising safety results, but more large-scale studies are needed to confirm this. ^{1 2 3 4 5}

What makes the drug JK07 unique for treating heart failure?

JK07 is unique because it targets GRK2, a protein that contributes to heart failure by disrupting heart cell signaling. By inhibiting GRK2, JK07 offers a novel approach that complements existing treatments and may improve heart function in ways other therapies do not. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

This trial is for adults aged 18-85 with heart failure. It's split into two groups: one with severely reduced pumping function (ejection fraction ≤ 40%) and another with moderately reduced or preserved function (>40% to ≤65%). Participants will be randomly given either a low or high dose of JK07, or a placebo.

Inclusion Criteria

Screening hemoglobin ≥ 9.0 g/dL

I have mild to moderate heart failure.

My heart's pumping ability is reduced (LVEF ≤ 40%).

Exclusion Criteria

I have used a breathing aid machine in the last 4 weeks, but not for sleep issues.

Sustained systolic BP < 90 mmHg and/or diastolic BP < 50 mmHg on at least 3 consecutive readings

I have not received IV inotropes or vasopressors in the last 8 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of JK07 or placebo administered by intravenous infusion

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

Treatment Details

Interventions

• JK07 (Other)

Trial Overview The study tests the safety and effectiveness of different doses of JK07 compared to a placebo in improving heart failure symptoms. It's double-blind, meaning neither the participants nor the researchers know who gets the real drug versus placebo during the trial.

Participant Groups

Group I: JK07 low dose Active Control 1 Intervention

JK07 administered by intravenous (IV) infusion

Group II: JK07 high dose Active Control 1 Intervention

JK07 administered by intravenous (IV) infusion

Group III: Placebo Placebo Group 1 Intervention

Placebo administered by intravenous (IV) infusion

Who Is Running the Clinical Trial?

Salubris Biotherapeutics Inc

Lead Sponsor

Trials

5

Recruited

710+

Findings from Research

In an 8-week study involving 63 patients with chronic heart failure and chronic kidney disease, a lower starting dose of patiromer (16.8 g/day) effectively maintained serum potassium levels within the target range while allowing for the safe initiation of spironolactone treatment.

Patiromer was well tolerated, with only a low incidence of adverse effects such as hypokalaemia (1.6%) and hypomagnesaemia (3.2%), demonstrating its safety and efficacy in preventing hyperkalaemia in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease. Pitt, B., Bushinsky, DA., Kitzman, DW., et al.[2021]

Interleukin-1 blockade shows promise as a potential anti-inflammatory treatment for heart failure, with early phase clinical trials indicating favorable safety and efficacy in reducing inflammation and improving heart function.

Despite these encouraging results, further large-scale clinical trials are necessary to confirm the effectiveness and safety of interleukin-1 blockade specifically for patients with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-1 Inhibition for the Prevention and Treatment of Heart Failure. Jafree, E., Del Buono, MG., Canada, JM., et al.[2023]

A phase II clinical trial is underway to evaluate the efficacy of anakinra, an IL-1 receptor antagonist, in improving peak oxygen consumption in 102 patients with acute decompensated heart failure and systemic inflammation over 24 weeks.

The trial aims to provide insights into how anakinra affects not only exercise capacity but also other heart function parameters and quality of life, potentially offering a novel treatment strategy for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study. Van Tassell, B., Mihalick, V., Thomas, G., et al.[2023]

In heart failure, chronic activation of the sympathetic nervous system leads to β-adrenergic receptor (βAR) dysfunction, primarily driven by the up-regulation of GPCR kinase 2 (GRK2), which negatively impacts heart function.

Targeting GRK2, particularly with the inhibitor peptide βARKct, has shown promise in improving heart function and structure in various animal models of heart failure, suggesting a potential new therapeutic strategy alongside existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting cardiac β-adrenergic signaling via GRK2 inhibition for heart failure therapy. Cannavo, A., Liccardo, D., Koch, WJ.[2022]

The incidence of heart failure with preserved ejection fraction (HFpEF) is likely increasing due to the lack of effective treatments, while heart failure with reduced ejection fraction (HFrEF) has better management options according to the 2021 European Society of Cardiology guidelines.

Current treatments targeting the Renin-Angiotensin-Aldosterone System (RAAS) are ineffective for HFpEF patients, highlighting the need for new therapeutic alternatives, such as drugs that stimulate the non-classic RAAS or emerging classes like SGLT2 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future therapeutic perspective in chronic heart failure. Mascolo, A., di Mauro, G., Cappetta, D., et al.[2022]

Heart failure affects around 5 million people in the U.S. and is linked to significant mortality, highlighting the urgent need for new treatment strategies.

Research indicates that inhibiting or deleting the PKCα gene in animal models shows promising protective effects against heart failure, suggesting that PKCα could be a valuable therapeutic target for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein kinase Cα as a heart failure therapeutic target. Liu, Q., Molkentin, JD.[2021]

GRK2 plays a crucial role in heart failure by regulating β-adrenergic receptors and other protective signaling pathways, and its elevated levels can lead to cardiac dysfunction.

Inhibition or genetic deletion of GRK2 in animal models has shown promise in protecting the heart from adverse remodeling and dysfunction, highlighting it as a potential therapeutic target for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GRK2 as a therapeutic target for heart failure. Cannavo, A., Komici, K., Bencivenga, L., et al.[2019]

Empagliflozin, originally developed for type 2 diabetes, has been shown to significantly reduce the risk of cardiovascular death and hospitalization for heart failure in patients with symptomatic chronic heart failure, regardless of their left ventricular ejection fraction, based on pivotal phase III trials.

The treatment not only improved cardiovascular outcomes but also enhanced health-related quality of life and was well tolerated, with a safety profile similar to that observed in diabetes patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin: A Review in Symptomatic Chronic Heart Failure. Frampton, JE.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Interleukin-1 Inhibition for the Prevention and Treatment of Heart Failure. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Comparative outcomes of heart failure among existent classes of anti-diabetic agents: a network meta-analysis of 171,253 participants from 91 randomized controlled trials. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Predicting adverse events during angiotensin receptor blocker treatment in heart failure: results from the HEAAL trial. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting cardiac β-adrenergic signaling via GRK2 inhibition for heart failure therapy. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Current and future therapeutic perspective in chronic heart failure. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Protein kinase Cα as a heart failure therapeutic target. [2021]

9. England pubmed.ncbi.nlm.nih.gov

GRK2 as a therapeutic target for heart failure. [2019]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Empagliflozin: A Review in Symptomatic Chronic Heart Failure. [2022]