LEVEL-2: LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF-2

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tenax Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2026-03-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Tenax Therapeutics, Inc

External identifiers

EU CT number

2025-522475-28-00

ClinicalTrials.gov

NCT05983250

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

"Efficacy: Evaluate the efficacy of 26 weeks of treatment with levosimendan (TNX-103) compared with placebo in patients with PH-HFpEF as measured by the change in 6-Minute Walk Distance (6 MWD)

Safety: To evaluate the safety and tolerability of oral levosimendan versus placebo"

Secondary objectives 1

1. The study will evaluate the effectiveness of 26 weeks of treatment with levosimendan compared with placebo in patients with PH-HFpEF in improving frequency and burden of heart failure symptoms, clinical events and physical activity limitations due to severity of heart failure symptoms.

Conditions and MedDRA coding

Pulmonary Hypertension (PH) with Heart Failure with preserved left ventricular ejection fraction (PH-HFpEF)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Men or women, ≥18 to 85 years of age.
2. 2. NYHA Class II or III or ambulatory NYHA Class IV symptoms.
3. 3. A diagnosis of WHO Group 2 PH-HFpEF with qualifying hemodynamics verified by right heart catheterization
4. 4. A qualifying echocardiogram performed within 45 days of Day 1 (ie within the Screening Period) showing a left ventricular ejection fraction ≥40%.
5. 5. Documentation of the absence of pulmonary thromboembolism by ventilation-perfusion scan, computed tomography pulmonary angiogram, or pulmonary angiography performed within 45 days of Day 1.
6. 6. A qualifying 6-MWD of at least 100 meters, but not more than 450 meters at Screening (within 45 days of Day 1) AND at the baseline 6-Minute Walk Test (6-MWT) on Day 1.

Exclusion criteria 8

1. 1. A diagnosis of PH WHO Groups 1, 3, 4, or 5.
2. 2. Echocardiographic evidence for hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or infiltrative cardiomyopathy.
3. 3. Structural heart repair or replacement of the aortic valve or mitral valve within the past 24 months. OR, planned valve intervention in the next 24 months. OR, the presence of echocardiographic findings of significant valve disease as assessed from the qualifying echocardiogram and defined as: a. Mitral valve disease grade ≥3 mitral regurgitation or ≥moderate mitral stenosis. b. Aortic valve disease grade ≥2 aortic regurgitation or ≥moderate aortic stenosis
4. 4. Any of the following clinical laboratory values within 45 days of Day 1 as specified: a. Hemoglobin <10 g/dL. b. Serum ALT or AST levels >3×ULN or total bilirubin >3×ULN. c. ECG with a heart rate-corrected QT interval using Fridericia’s formula >450 msec for males and >470 msec for females at Screening in the absence of a bundle branch block or ventricularly paced rhythm. d. Platelet count <75,000/mm3.
5. 5. Any of the following structural conditions that may compromise pulmonary function: a. Congenital abnormalities of the lungs, thorax or diaphragm, that may significantly contribute to the severity of PH in the opinion of the Investigator. b. A full or partial pneumonectomy. c. Previous therapeutic radiation of lungs or mediastinum.
6. 6. Recent documentation of significant underlying lung disease.
7. 7. Documentation of pulmonary thromboembolism in the last 12 months by a ventilation-perfusion scan, CT pulmonary angiogram, or a pulmonary angiography with an interpretation other than a normal or low probability result.
8. 8. Cardiovascular comorbidities, which include the following: a. Symptomatic or untreated coronary artery disease. b. Acute coronary syndrome, coronary artery bypass graft, or percutaneous coronary intervention; any within 180 days of Day 1. c. Uncontrolled resting heart rate due to atrial fibrillation or atrial flutter at the time of the Screening ambulatory cardiac monitoring. d. History of untreated serious life-threatening or hemodynamically significant arrhythmia. e. History of or anticipated heart transplant or ventricular assist device implantation. f. Anticipated implantation of a pacemaker, or pacemaker implantation within 30 days of Screening. g. Occurrence of myocardial infarction due to epicardial coronary artery disease within 180 days of Day 1. h. Uncontrolled systemic hypertension as evidenced by sitting systolic BP >170 mmHg after a period of rest during the Screening Period. i. Stroke within 90 days of Day 1. j. Systolic BP <100 mmHg at Screening and Day 1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy: Change from baseline in 6-MWD (Day 1 to Week 26). Safety: Incidence of AEs, SAEs, physical examinations, vital signs, clinical laboratory values, ECGs, heart rate and rhythm as determined by cardiac monitoring and AESI (Day 1 to Week 26)

Secondary endpoints 4

1. 1. Change in KCCQ-TSS (Day 1 to Week 26).
2. 2. Number of Clinical Worsening Events (Day 1 to Week 26). Clinical Worsening Events are defined as: a. Unplanned hospitalization due to a cardiopulmonary indication OR Urgent outpatient visits for the administration of IV diuretics. b. Deaths (caused by clinical conditions directly related to cardiovascular events).
3. 3. Time to first occurrence of a Clinical Worsening Event (Day 1 to Week 26).
4. 4. Change in NYHA Functional Class (Day 1 to Week 26).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tenax Therapeutics Inc.

Sponsor organisation

Tenax Therapeutics Inc.

Address

101 Glen Lennox Drive Suite 300

City

Chapel Hill

Postcode

27517-4089

Country

United States

Scientific contact point

Organisation

Tenax Therapeutics Inc.

Contact name

Stuart Rich

Public contact point

Organisation

Tenax Therapeutics Inc.

Contact name

Akshata Ashokkumar

Third parties 6

Locations

9 EU/EEA countries · 52 investigational sites

By country

Investigational sites

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 125 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications