Levosimendan for Pulmonary Hypertension with Heart Failure

(LEVEL Trial)

Recruiting at 95 trial locations

Overseen By Douglas Hay, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Tenax Therapeutics, Inc.

Disqualifiers: PH WHO Groups 1, 3, 4, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an oral medication called TNX-103 (also known as Levosimendan) to determine if it helps people with pulmonary hypertension and heart failure improve their ability to walk further over time. The study compares TNX-103 to a placebo (a pill with no active medication) to assess its effectiveness. Suitable participants have been diagnosed with a specific type of heart failure and pulmonary hypertension and experience symptoms that affect daily activities like walking. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that levosimendan, the active ingredient in TNX-103, is generally safe. In past studies, oral administration of levosimendan was safe and well-tolerated for 6 to 8 weeks in patients with conditions similar to those in this trial. These patients had received the drug intravenously for over two years without major safety issues. This suggests that levosimendan is usually well-tolerated, with serious side effects being rare. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TNX-103 for pulmonary hypertension with heart failure because it offers a new mechanism of action compared to the standard treatments like endothelin receptor antagonists and phosphodiesterase-5 inhibitors. TNX-103 contains oral levosimendan, which enhances the heart's ability to pump blood more effectively by sensitizing cardiac muscle to calcium without increasing oxygen demand. This could potentially lead to quicker symptom relief and improved quality of life for patients. Furthermore, its oral delivery method makes it more convenient than some existing options that require injections or infusions.

What evidence suggests that TNX-103 might be an effective treatment for pulmonary hypertension with heart failure?

Research has shown that levosimendan, the main ingredient in TNX-103, may help treat pulmonary hypertension with heart failure. Patients who used levosimendan in the past have been able to exercise more. It improves heart pumping, which can enhance blood flow and ease symptoms. Earlier studies demonstrated that levosimendan helped patients walk longer distances, indicating its effectiveness for this condition. In this trial, participants will receive either TNX-103 or a placebo. This suggests that TNX-103 could help people with pulmonary hypertension and heart failure feel better and be more active. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with WHO Group 2 PH-HFpEF, a heart condition where the left side of the heart doesn't pump well leading to high blood pressure in lungs. Participants need a specific range of walking ability and stable medication use. Pregnant or breastfeeding women can't join, and those who can have children must use effective birth control.

Inclusion Criteria

I have been diagnosed with a specific type of high blood pressure in the lungs due to heart failure.

I am a woman who can have children and have not had sex or used effective birth control for 90 days.

My heart or lung condition medication dose has been stable for over 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive oral levosimendan or placebo for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

92 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• TNX-103

Trial Overview The study tests TNX-103 (levosimendan) against a placebo in patients with PH-HFpEF by measuring changes in their walking distance over six minutes from Day 1 to Week 12. The goal is to see if TNX-103 improves exercise capacity compared to no active treatment.

How Is the Trial Designed?

Group I: TNX-103 Active Control 1 Intervention

oral levosimendan

Group II: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Tenax Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

1,200+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Medpace, Inc.

Industry Sponsor

Trials

98

Recruited

30,400+

Dr. August J. Troendle

Medpace, Inc.

Chief Executive Officer since 1992

MD from the University of Maryland, School of Medicine; MBA from Boston University

Dr. Reinilde Heyrman

Medpace, Inc.

Chief Medical Officer since 2017

MD

Published Research Related to This Trial

Levosimendan is an effective treatment for acute severe decompensated heart failure, showing a 30% increase in cardiac output and significant improvements in hemodynamic response compared to placebo and dobutamine.

It is generally well tolerated with a safety profile similar to placebo, and may have a lower risk of cardiac rhythm disorders compared to dobutamine, while also potentially reducing mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levosimendan: a review of its use in the management of acute decompensated heart failure. Innes, CA., Wagstaff, AJ.[2018]

Levosimendan is a calcium-sensitizing agent that has shown effectiveness and safety in treating pulmonary arterial hypertension and pulmonary hypertension related to left heart disease, making it a promising addition to existing therapies.

This review highlights the unique properties of levosimendan, including its inotropic and pulmonary vasodilator effects, which may improve outcomes for patients suffering from this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Levosimendan in Patients with Pulmonary Hypertension: What is the Current Evidence? Masarone, D., Kittleson, M., Pollesello, P., et al.[2023]

Levosimendan is a promising treatment option for right ventricular failure in pulmonary hypertension due to its unique properties as a calcium sensitizer, which enhances heart muscle contraction and dilates blood vessels.

Currently, there are no approved therapies specifically targeting the failing right ventricle in pulmonary hypertension, highlighting the potential significance of levosimendan in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levosimendan in pulmonary hypertension and right heart failure. Hansen, MS., Andersen, A., Nielsen-Kudsk, JE.[2020]

In a rodent model of severe verapamil poisoning, levosimendan effectively increased cardiac output (CO) similar to calcium chloride (CaCl2), but did not improve blood pressure (BP) from the time of maximal toxicity.

The study suggests that levosimendan's mechanism of action, which includes peripheral vasodilation, may counteract its benefits by exacerbating hypotension during verapamil toxicity, indicating a complex interaction between these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of experimental verapamil poisoning with levosimendan utilizing a rodent model of drug toxicity. Graudins, A., Najafi, J., Rur-SC, MP.[2018]

Levosimendan significantly enhances right ventricular contractility and overall cardiac performance in a study involving eight pigs, without affecting pulmonary vascular tone, suggesting its potential utility in right ventricular dysfunction.

The drug also improved left ventricular efficiency and cardiac output while reducing systemic vascular resistance, indicating its positive inotropic effects, although further research is needed to explore its effects in conditions of pulmonary vasoconstriction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of levosimendan on right ventricular function and ventriculovascular coupling in open chest pigs. Leather, HA., Ver Eycken, K., Segers, P., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05983250

Study Details | NCT05983250 | LEVosimendan to Improve ... This study will evaluate the efficacy of TNX-103 (oral levosimendan) compared with placebo in subjects with PH-HFpEF as measured by the change in 6-Minute Walk ...

2. investors.tenaxthera.com investors.tenaxthera.com/news-releases/news-release-details/tenax-therapeutics-announces-fda-clearance-ind-tnx-103-oral

Release Details Tenax Therapeutics Announces FDA Clearance of IND for TNX-103 (oral levosimendan) for the Treatment of Pulmonary Hypertension with Heart Failure with Preserved ...

3. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/MEDP/pressreleases/35739452/tenax-therapeutics-advances-phase-3-study-on-levosimendan-for-ph-hfpef/

Tenax Therapeutics Advances Phase 3 Study on ... The study aims to assess the effectiveness of TNX-103 (oral levosimendan) in improving exercise capacity in patients with PH-HFpEF, measured by ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7374352/

Levosimendan Efficacy and Safety: 20 years of SIMDAX in ... A Phase II regulatory clinical trial is currently underway in the US on the repeated use of IV levosimendan for pulmonary hypertension in patients with HF and ...

5. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/irb231834

CLINICAL TRIAL / NCT05983250 This study will evaluate the efficacy of TNX-103 (oral levosimendan) compared with placebo in subjects with PH-HFpEF as measured by the change in 6-Minute Walk ...

6. tenaxthera.com tenaxthera.com/clinical-trials/

Clinical Trials We believe levosimendan's mechanism of action may be uniquely suited to treating PH-HFpEF. The active drug comes with a well-known safety profile ...

7. biospace.com biospace.com/press-releases/tenax-therapeutics-expands-phase-3-level-program-advancing-two-tnx-103-oral-levosimendan-registrational-studies-for-the-treatment-of-ph-hfpef

Tenax Therapeutics Expands Phase 3 LEVEL Program ... Results of Tenax Therapeutics' Phase 2 HELP study of levosimendan in patients with HFpEF demonstrated that IV levosimendan (TNX-101) produces ...

8. docs.publicnow.com docs.publicnow.com/682CA61ABFBB151F07E8E3050FF2F1BCBDA80688

TENAX THERAPEUTICS Oral levosimendan was safe and well tolerated over a 6-8 week period in patients with PH-HFpEF who had been receiving IV levosimendan as an outpatient >2 yrs.