JTT-861 for Heart Failure

(POWER-HF Trial)

Recruiting at 98 trial locations

Overseen By Takanori Nemoto, M.S.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Akros Pharma Inc.

Must be taking: RAAS inhibitors, β-blockers

Disqualifiers: Recent MI, Unstable angina, Renal insufficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called JTT-861 to determine its effectiveness for people with heart failure with reduced ejection fraction, a condition where the heart doesn't pump well. The goal is to assess the safety and effectiveness of JTT-861 when taken once daily for 12 weeks. Participants will receive either one of two doses of JTT-861 or a placebo, which contains no active medicine. This trial suits those who have experienced heart failure symptoms for at least 90 days, are on stable heart failure medication, and have a specific heart condition with reduced pumping ability. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires participants to be on stable, guideline-directed therapy for heart failure, so you will need to continue your current heart failure medications.

Is there any evidence suggesting that JTT-861 is likely to be safe for humans?

Research has shown that JTT-861 has been tested for safety in people with heart failure. Although specific safety details from those studies are not provided, the treatment has advanced to its current phase, indicating that earlier tests found it generally safe for humans.

In these studies, participants received JTT-861 for 12 weeks. When a treatment reaches this phase, it typically indicates some level of safety demonstrated in earlier research. However, individual reactions can vary, and joining a trial involves risks. Always consult your doctor to understand what this might mean for you. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Unlike the standard heart failure treatments, which often include ACE inhibitors, beta-blockers, and diuretics, JTT-861 is unique because it targets a novel mechanism of action. Researchers are excited about JTT-861 because it offers a new approach to managing heart failure, where current options primarily focus on symptom relief and slowing disease progression. This experimental treatment is in capsule form and is designed to be taken orally once daily, offering potential convenience and ease of use for patients. By exploring this new pathway, JTT-861 could provide benefits beyond those of existing therapies, potentially improving outcomes for those living with heart failure.

What evidence suggests that JTT-861 might be an effective treatment for heart failure?

Research has shown that JTT-861 may help treat heart failure with reduced ejection fraction (HFrEF). Early results suggest this treatment could improve heart function by helping the heart pump blood more effectively. In earlier studies, patients taking JTT-861 experienced better heart-related symptoms and overall heart health. In this trial, participants will receive either JTT-861 at different doses or a placebo to further evaluate its effectiveness. These findings offer hope that JTT-861 might be a new way to manage heart failure symptoms. However, more research is needed to confirm these early positive results. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for people who have had heart failure symptoms for at least 90 days, are in NYHA class II or III, and have been on stable heart failure medication as per guidelines. They should also have a left ventricular ejection fraction of 35% or less and certain levels of NT-pro-BNP. People with recent heart attacks, unstable angina, recent or planned heart surgeries, severe kidney issues, or other specific cardiovascular conditions cannot participate.

Inclusion Criteria

My heart condition limits my physical activity but I can still perform light tasks.

I have been on a stable heart failure treatment for over 4 weeks, following major heart association guidelines.

I have been diagnosed with heart failure for at least 90 days.

Exclusion Criteria

I had a heart attack or unstable chest pain in the last 90 days.

I have had heart surgery or a procedure to improve blood flow to the heart within the last 3 months.

I am currently receiving extra treatment for worsening heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive JTT-861 or placebo once daily for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• JTT-861

Trial Overview The study tests JTT-861 capsules against placebo capsules over a period of 12 weeks to see if they're effective and safe for treating chronic heart failure with reduced ejection fraction (HFrEF). Participants must be on stable medical therapy according to current guidelines while taking part in the trial.

How Is the Trial Designed?

Group I: Placebo Experimental Treatment 1 Intervention

Placebo Capsules orally once daily for 12 weeks

Group II: JTT-861 Dose 2 Experimental Treatment 1 Intervention

JTT-861 Capsules Dose 2 orally once daily for 12 weeks

Group III: JTT-861 Dose 1 Experimental Treatment 1 Intervention

JTT-861 Capsules Dose 1 orally once daily for 12 weeks

Who Is Running the Clinical Trial?

Akros Pharma Inc.

Lead Sponsor

Trials

24

Recruited

2,800+

ICON Clinical Research

Industry Sponsor

Trials

52

Recruited

15,100+

Published Research Related to This Trial

Endothelin-1 (ET-1) plays a significant role in heart failure, and targeting its activity with endothelin receptor blockers may offer new therapeutic strategies for patients, despite current treatments showing limited effectiveness.

Most existing studies on endothelin receptor blockers have involved small patient groups and short follow-up periods, focusing on surrogate endpoints rather than hard clinical outcomes, with larger trials currently underway to determine the best approach for receptor blockade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of endothelins in congestive heart failure. Moe, GW., Rouleau, JL., Nguyen, QT., et al.[2014]

In a rat model of chronic heart failure (CHF), endothelin-1 (ET-1) levels were significantly elevated compared to control rats, indicating a potential role of endothelin in the progression of heart failure.

The endothelin receptor antagonist bosentan effectively reduced mean arterial pressure in CHF rats, suggesting that targeting endothelin could be a promising therapeutic strategy for managing heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of endothelin in the maintenance of blood pressure in conscious rats with chronic heart failure. Acute effects of the endothelin receptor antagonist Ro 47-0203 (bosentan). Teerlink, JR., Löffler, BM., Hess, P., et al.[2019]

A study analyzing 114,005 adverse event reports found that JAK inhibitors (baricitinib, tofacitinib, and upadacitinib) are associated with an increased risk of deep vein thrombosis (DVT), particularly in older adults (ages 65-100) and males.

Baricitinib and tofacitinib showed stronger signals for DVT compared to upadacitinib, indicating a need for further research to confirm these safety concerns and understand the mechanisms involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the risk of deep vein thrombosis with JAK inhibitors: a disproportionality analysis using FDA Adverse Event Reporting System Database (FAERS). Mytheen, S., Varghese, A., Joy, J., et al.[2023]

Endothelin-1 (ET-1) is implicated in chronic heart failure, with elevated levels correlating to worse heart function, suggesting that targeting ET-1 could be beneficial for treatment.

Both mixed and selective ET-1 receptor antagonists have shown promise in improving heart function in chronic heart failure, indicating potential for similar benefits in acute heart failure, but further clinical trials are needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and perspective of endothelin-1 antagonism in acute heart failure. Kiowski, W., Suetsch, G., Oechslin, E., et al.[2019]

JAK inhibitors (JAKi) are showing efficacy comparable to or better than traditional biologic treatments for inflammatory arthritis, with tofacitinib and baricitinib being the first generation approved for use.

Next-generation selective JAK1 inhibitors like upadacitinib and filgotinib are promising, but all JAKi share a safety concern regarding increased risk of viral infections, particularly herpes zoster, highlighting the need for ongoing post-marketing surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The new entries in the therapeutic armamentarium: The small molecule JAK inhibitors. Bechman, K., Yates, M., Galloway, JB.[2023]

Endothelin-1 (ET-1) is a significant prognostic marker in severe heart conditions, such as heart failure and myocardial infarction, indicating its role in adverse cardiovascular outcomes.

Clinical trials are currently investigating the effects of ET receptor antagonists, which may counteract the harmful effects of ET-1, such as increased blood pressure and vascular hypertrophy, in patients with heart failure and other cardiovascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endothelin receptor antagonists in cardiology clinical trials. Neunteufl, T., Berger, R., Pacher, R.[2019]

ABT-494, a selective JAK-1 inhibitor, demonstrated significant efficacy in improving symptoms of moderate-to-severe rheumatoid arthritis in patients who had inadequate responses to anti-TNF agents, with 53-71% of patients achieving a 20% improvement in symptoms (ACR20) compared to 34% in the placebo group after 12 weeks.

The treatment was well-tolerated, with common side effects including headache and infections, but no serious infections or deaths reported, indicating a favorable safety profile similar to other medications in its class.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Therapy. Kremer, JM., Emery, P., Camp, HS., et al.[2022]

In a review of 66 randomized clinical trials involving 38,574 patients, JAK inhibitors showed a numerically higher risk of venous thromboembolism (VTE) compared to active comparators, particularly in studies with follow-up durations of 12 months or more.

No increased risk of VTE was observed when comparing JAK inhibitors to placebo, and while there was a trend towards increased major adverse cardiac events (MACE), it did not reach statistical significance, indicating a need for further long-term studies to better understand the safety of JAK inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular and Venous Thromboembolic Risk With Janus Kinase Inhibitors in Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis of Randomized Trials. Maqsood, MH., Weber, BN., Haberman, RH., et al.[2023]

Despite advancements in heart failure treatments like beta-blockers and renin-angiotensin system antagonists, there remains a significant need for more effective therapies for many patients.

Recent research has identified new potential targets for heart failure therapy based on a better understanding of disease mechanisms, emphasizing the importance of addressing key issues to enhance the success of new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug discovery for heart failure: a new era or the end of the pipeline? Kaye, DM., Krum, H.[2007]

The new endothelin receptor antagonist T-0201 effectively inhibits the blood pressure response to endothelin-1 in normal dogs, demonstrating its potential as a treatment for congestive heart failure (CHF) by blocking both ETA and ETB receptors.

In a chronic study with dogs suffering from CHF, T-0201 significantly improved cardiorenal function and prevented further deterioration, indicating its efficacy in managing CHF over a 15-day treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic effects of a novel, orally active endothelin receptor antagonist, T-0201, in dogs with congestive heart failure. Ohnishi, M., Wada, A., Tsutamoto, T., et al.[2019]

ABT-494, a selective JAK 1 inhibitor, demonstrated favorable pharmacokinetics and safety in healthy subjects and those with rheumatoid arthritis, with mild to moderate side effects and no significant drug interactions with methotrexate.

The study involved 56 healthy participants for single dosing and 44 for multiple dosing, showing that ABT-494 had a manageable elimination half-life and dose-proportional exposure, supporting its potential for further testing in phase IIb trials for rheumatoid arthritis and Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis. Mohamed, MF., Camp, HS., Jiang, P., et al.[2018]

A study involving 399 chronic heart failure patients showed that implementing a computer-based reminder system for physicians improved guideline-based beta-blocker prescriptions by 12.3% after one year.

The use of the reminder system also increased the prescription of aldosterone antagonists for severe heart failure from 35% to 44.2%, indicating a positive impact on medication adherence to treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative strategy for implementing chronic heart failure guidelines among family physicians in different healthcare settings in Berlin. Braun, V., Heintze, C., Rufer, V., et al.[2022]

Elevated levels of endothelin-1 are linked to chronic heart failure, and using bosentan, an endothelin-1 receptor antagonist, has shown promising improvements in heart function and hemodynamics in patients when added to standard therapy.

Short-term treatment with bosentan reduced the activity of the renin-angiotensin system and lowered plasma aldosterone levels, suggesting a beneficial effect on heart failure management, but further long-term studies are needed to confirm its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of bosentan in patients with chronic heart failure. Kiowski, W., Sütsch, G., Oechslin, E., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06017609

Evaluate Efficacy, Safety and Tolerability of JTT-861 in ... This study will evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-861 administered once daily for 12 weeks in subjects with heart ...

2. ctv.veeva.com ctv.veeva.com/study/evaluate-efficacy-safety-and-tolerability-of-jtt-861-in-subjects-with-heart-failure-with-reduced-ej

Evaluate Efficacy, Safety and Tolerability of JTT-861 in ... This study will evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-861 administered once daily for 12 weeks in subjects with heart failure ...

3. clinicaltrials.eu clinicaltrials.eu/trial/study-on-jtt-861-for-patients-with-heart-failure-with-reduced-ejection-fraction/

Study on JTT-861 for Patients with Heart Failure with ... This clinical trial examines the efficacy and safety of JTT-861, a potential treatment for Heart Failure with Reduced Ejection Fraction (HFrEF).

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06017609/evaluate-efficacy-safety-and-tolerability-of-jtt-861-in-subjects-with-heart-failure-with-reduced-ejection-fraction

Evaluate Efficacy, Safety and Tolerability of JTT-861 in ... This study will evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-861 administered once daily for 12 weeks in subjects with heart failure.

5. withpower.com withpower.com/trial/phase-2-heart-failure-7-2023-ade95

JTT-861 for Heart Failure (POWER-HF Trial) This study will evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-861 administered once daily for 12 weeks in subjects with heart ...

6. trialx.com trialx.com/clinical-trials/listings/242980/evaluate-efficacy-safety-and-tolerability-of-jtt-861-in-subjects-with-heart-failure-with-reduced-ejection-fraction/

Evaluate Efficacy, Safety and Tolerability of JTT-861 in ... This study will evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-861 administered once daily for 12 weeks in subjects ...