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

NCT07288398 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: TNX-103-072025-522475-28-00
• Study Type: interventional
• Target: 540
• Locations: 15 countries
• Sites: 92

Brief Summary

The purpose of this study is to assess the efficacy and safety of the study drug, levosimendan (given orally), compared to placebo in participants with pulmonary hypertension with heart failure with preserved left ventricular ejection fraction (PH-HFpEF) as measured by the change in 6-Minute Walk Distance.

Conditions

Pulmonary Hypertension Associated With HFpEF

Keywords

PH-HFpEF; levosimendan; HFpEF; Heart Failure; Pulmonary Hypertension Group 2

Outcome Measures

Primary Outcomes (1)

• 6-Minute Walk Distance (6MWD)

  Change in 6-minute walk distance

  26 weeks

Secondary Outcomes (4)

• KCCQ (Kansas City Cardiomyopathy Questionnaire) score is a standardized measure that ranges from 0 to 100, where a higher score indicates better health.

  26 weeks

• Clinical Worsening Events

  26 weeks

• Clinical Worsening Event

  26 weeks

• NYHA (New York Heart Association) classification assesses and categorizes a patient's physical ability and symptoms into four classes, the lower the classification, the least impact on physical activity.

  26 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching placebo (oral)

Drug: Placebo

TNX-103

ACTIVE COMPARATOR

Oral levosimendan

Drug: TNX-103

Interventions

TNX-103 DRUG

Oral levosimendan

TNX-103

Placebo DRUG

Matching placebo (oral)

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women, ≥18 to 85 years of age
• NYHA Class II or III or ambulatory NYHA Class IV symptoms
• A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying hemodynamics verified by right heart catheterization (RHC)
• A qualifying baseline RHC
• A qualifying echocardiogram
• A qualifying 6-MWD
• A 48-hour ambulatory cardiac rhythm monitor during the Screening Period
• Requirements related to child bearing potential, contraception, and egg/sperm donation)

You may not qualify if:

• A diagnosis of PH WHO Groups 1, 3, 4, or 5
• Echocardiographic evidence for hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or infiltrative cardiomyopathy
• Structural heart repair or replacement of the aortic valve or mitral valve (surgical or percutaneous) OR, planned valve intervention OR, the presence of significant valve disease
• A diagnosis of pre-existing lung disease
• History of severe allergic or anaphylactic reaction or hypersensitivity to the excipients in the investigational product
• Major surgery within 60 days
• Prior heart, lung, or heart-lung transplants or life expectancy of \<12 months
• History of clinically significant other diseases that may limit or complicate participation in the study

Sponsors & Collaborators

• Tenax Therapeutics, Inc.: lead

Study Sites (92)

Tenax Investigational Site

Alexander City, Alabama, 35010, United States

RECRUITING

Tenax Investigational Site

Tamarac, Florida, 33321, United States

NOT YET RECRUITING

Tenax Investigational Site

Mount Prospect, Illinois, 60056, United States

NOT YET RECRUITING

Tenax Investigational Site

Peoria, Illinois, 61636, United States

RECRUITING

Tenax Investigational Site

New Orleans, Louisiana, 70115-6969, United States

RECRUITING

Tenax Investigational Site

West Monroe, Louisiana, 71291, United States

RECRUITING

Tenax Investigational Site

Ypsilanti, Michigan, 48197, United States

NOT YET RECRUITING

Tenax Investigational Site

Reno, Nevada, 89502, United States

RECRUITING

Tenax Investigational Site

New York, New York, 10032, United States

NOT YET RECRUITING

Tenax Investigational Site

Winston-Salem, North Carolina, 27101, United States

RECRUITING

Tenax Investigational Site

Allentown, Pennsylvania, 18105, United States

NOT YET RECRUITING

Tenax Investigational Site

Wynnewood, Pennsylvania, 19096-3450, United States

NOT YET RECRUITING

Tenax Investigational Site

Nashville, Tennessee, 37205, United States

RECRUITING

Tenax Investigational Site

Austin, Texas, 78705, United States

RECRUITING

Tenax Investigational Site

Dallas, Texas, 75390, United States

RECRUITING

Tenax Investigational Site

Houston, Texas, 77002, United States

RECRUITING

Tenax Investigational Site

Norfolk, Virginia, 23507-1904, United States

NOT YET RECRUITING

Tenax Investigational Site

Marshfield, Wisconsin, 54449, United States

NOT YET RECRUITING

Tenax Investigational Site

Buenos Aires, Buenos Aires F.D., 1280, Argentina

NOT YET RECRUITING

Tenax Investigational Site

Corrientes, Corrientes Province, W3400AMZ, Argentina

NOT YET RECRUITING

Tenax Investigational Site

San Luis, San Luis Province, D5702JRS, Argentina

NOT YET RECRUITING

Tenax Investigational Site

Braunau am Inn, 5280, Austria

NOT YET RECRUITING

Tenax Investigational Site

Graz, 8036, Austria

NOT YET RECRUITING

Tenax Investigational Site

Klagenfurt, 9020, Austria

NOT YET RECRUITING

Tenax Investigational Site

Sankt Pölten, 3100, Austria

NOT YET RECRUITING

Tenax Investigational Site

Vienna, 1100, Austria

NOT YET RECRUITING

Tenax Investigational Site

Salvador, Estado de Bahia, 40170-130, Brazil

NOT YET RECRUITING

Tenax Investigational Site

Belo Horizonte, Minas Gerais, 30220, Brazil

NOT YET RECRUITING

Tenax Investigational Site

Curitiba, Paraná, 80215-901, Brazil

NOT YET RECRUITING

Tenax Investigational Site

Ribeirão Preto, São Paulo, 14026-020, Brazil

NOT YET RECRUITING

Tenax Investigational Site

Pleven, 5800, Bulgaria

NOT YET RECRUITING

Tenax Investigational Site

Sofia, 1407, Bulgaria

NOT YET RECRUITING

Tenax Investigational Site

Sofia, 1431, Bulgaria

NOT YET RECRUITING

Tenax Investigational Site

Sofia, 1750, Bulgaria

NOT YET RECRUITING

Tenax Investigational Site

Ostrava, 72880, Czechia

NOT YET RECRUITING

Tenax Investigational Site

Prague, 10034, Czechia

NOT YET RECRUITING

Tenax Investigational Site

Prague, 15006, Czechia

NOT YET RECRUITING

Tenax Investigational Site

Le Kremlin-Bicêtre, 94270, France

NOT YET RECRUITING

Tenax Investigational Site

Montpellier, 34295, France

NOT YET RECRUITING

Tenax Investigational Site

Nantes, 44007, France

NOT YET RECRUITING

Tenax Investigational Site

Nice, 06001, France

NOT YET RECRUITING

Tenax Investigational Site

Pau, 64000, France

NOT YET RECRUITING

Tenax Investigational Site

Bad Bevensen, 29549, Germany

NOT YET RECRUITING

Tenax Investigational Site

Bad Nauheim, 61231, Germany

NOT YET RECRUITING

Tenax Investigational Site

Berlin, 12683, Germany

NOT YET RECRUITING

Tenax Investigational Site

Dresden, 01307, Germany

NOT YET RECRUITING

Tenax Investigational Site

Hamburg, 20251, Germany

NOT YET RECRUITING

Tenax Investigational Site

Jena, 07747, Germany

NOT YET RECRUITING

Tenax Investigational Site

Budapest, 1122, Hungary

NOT YET RECRUITING

Tenax Investigational Site

Budapest, 1134, Hungary

NOT YET RECRUITING

Tenax Investigational Site

Debrecen, 4032, Hungary

NOT YET RECRUITING

Tenax Investigational Site

Szeged, 6275, Hungary

NOT YET RECRUITING

Tenax Investigational Site

Acquaviva delle Fonti, 70021, Italy

NOT YET RECRUITING

Tenax Investigational Site

Messina, 98125, Italy

NOT YET RECRUITING

Tenax Investigational Site

Milan, 20132, Italy

NOT YET RECRUITING

Tenax Investigational Site

Milan, 20138, Italy

NOT YET RECRUITING

Tenax Investigational Site

Milan, 20149, Italy

NOT YET RECRUITING

Tenax Investigational Site

Pavia, 27100, Italy

NOT YET RECRUITING

Tenax Investigational Site

Pisa, 56126, Italy

NOT YET RECRUITING

Tenax Investigational Site

Roma, 00168, Italy

NOT YET RECRUITING

Tenax Investigational Site

Rozzano, 20089, Italy

NOT YET RECRUITING

Tenax Investigational Site

Poznan, 61848, Poland

NOT YET RECRUITING

Tenax Investigational Site

Wroclaw, 50556, Poland

NOT YET RECRUITING

Tenax Investigational Site

Wroclaw, 50891, Poland

NOT YET RECRUITING

Tenax Investigational Site

Cheongju-si, 28644, South Korea

NOT YET RECRUITING

Tenax Investigational Site

Gwangju, 61469, South Korea

NOT YET RECRUITING

Tenax Investigational Site

Incheon, 21565, South Korea

NOT YET RECRUITING

Tenax Investigational Site

Seoul, 03080, South Korea

NOT YET RECRUITING

Tenax Investigational Site

Seoul, 08308, South Korea

NOT YET RECRUITING

Tenax Investigational Site

Wŏnju, 26426, South Korea

NOT YET RECRUITING

Tenax Investigational Site

Barcelona, 08003, Spain

NOT YET RECRUITING

Tenax Investigational Site

Barcelona, 08035, Spain

NOT YET RECRUITING

Tenax Investigational Site

Barcelona, 08036, Spain

NOT YET RECRUITING

Tenax Investigational Site

Lugo, 27003, Spain

NOT YET RECRUITING

Tenax Investigational Site

Madrid, 28041, Spain

NOT YET RECRUITING

Tenax Investigational Site

Madrid, 28046, Spain

NOT YET RECRUITING

Tenax Investigational Site

Madrid, 28055, Spain

NOT YET RECRUITING

Tenax Investigational Site

Marbella, 29603, Spain

NOT YET RECRUITING

Tenax Investigational Site

Málaga, 29010, Spain

NOT YET RECRUITING

Tenax Investigational Site

Pamplona, 31008, Spain

NOT YET RECRUITING

Tenax Investigational Site

Salamanca, 37007, Spain

NOT YET RECRUITING

Tenax Investigational Site

Seville, 41009, Spain

NOT YET RECRUITING

Tenax Investigational Site

Toledo, 45007, Spain

NOT YET RECRUITING

Tenax Investigational Site

Valencia, 46010, Spain

NOT YET RECRUITING

Tenax Investigational Site

Valencia, 46020, Spain

NOT YET RECRUITING

Tenax Investigational Site

Kaohsiung City, 80756, Taiwan

NOT YET RECRUITING

Tenax Investigational Site

Kaohsiung City, 813414, Taiwan

NOT YET RECRUITING

Tenax Investigational Site

Taipei, 10449, Taiwan

NOT YET RECRUITING

Tenax Investigational Site

Taipei, 110, Taiwan

NOT YET RECRUITING

Tenax Investigational Site

Taoyuan District, 33305, Taiwan

NOT YET RECRUITING

Tenax Investigational Site

Cambridge, CB233RE, United Kingdom

NOT YET RECRUITING

Tenax Investigational Site

Swindon, SN36BB, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Central Study Contacts

Akshata Ashokkumar

CONTACT

(919) 855-2118; a.ashokkumar@tenaxthera.com

Katelyn Jansson

CONTACT

(919) 855-2119; k.jansson@tenaxthera.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: December 17, 2025
• Study Start: March 3, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

PL (3); FR (5); AR (3); CZ (3); BR (4); AU (5); DE (6); KR (6); IT (9); US (18); GB (2); TW (5); BU (4); HU (4); ES (15)