Summary

Eligibility
for people ages 18-85 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
completion around

Description

Summary

This study will evaluate the efficacy of TNX-103 (levosimendan) compared with placebo in subjects with PH-HFpEF as measured by the change in 6-Minute Walk Distance (6 MWD; Day 1 to Week 12).

Official Title

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction (PH-HFpEF)

Details

This is a Phase 3, double-blind, randomized, placebo-controlled study of levosimendan in patients with PH-HFpEF. There will be a Screening Period of up to 30 days. Subjects will provide written informed consent prior to completing any study procedures. Upon meeting all eligibility criteria, patients will continue to the 12-week randomized, double-blind treatment phase. Approximately 152 subjects will be randomized in a 1:1 ratio to receive an oral dose of levosimendan or placebo 2 mg/day for Weeks 1 to 4 and 3 mg/day for Weeks 5 to 12. Subjects will return to the clinical site at Weeks 4, 8, and 12.

All randomized subjects will have the option to enter the 92-week OLE following the completion of all study events at Week 12.

Keywords

Pulmonary Hypertension, HFpEF, Pulmonary hypertension group 2, PH-HFpEF, Hypertension, TNX-103

Eligibility

You can join if…

Open to people ages 18-85

  1. Men or women, greater than or equal to18 to 85 years of age.
  2. NYHA Class II or III or ambulatory NYHA class IV symptoms.
  3. A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying hemodynamics
  4. A qualifying Baseline RHC performed within 120 days. The RHC can be a historical RHC done prior to study consent.
  5. A qualifying echocardiogram performed within 30 days showing an LVEF greater than or equal to 40%
  6. A qualifying 6-MWD of at least 100 meters, but not more than 450 meters at Screening
  7. A 48-hour ambulatory cardiac rhythm monitor during the Screening Period to establish the resting heart rate (HR) and rhythm.
  8. Chronic medications for heart failure with preserved ejection fraction (HFpEF) or other serious underlying cardiac or pulmonary conditions should be administered at a stable dose for greater than or equal to 30 days prior to the day of the Baseline 6-MWT.
  9. Female subjects of childbearing potential must have a negative urine pregnancy test result at the Screening Visit and a negative urine pregnancy test and must not be pregnant, lactating, or planning a pregnancy from the Screening Visit to 7 months after the last dose of study drug.

    10. Female subjects of childbearing potential will be included if they are either sexually

    inactive (abstinent) for 90 days prior to the first dose of study drug, or are using a highly effective birth control method

    11. Female subjects of nonchildbearing potential will be included if they meet the

    following definition of nonchildbearing potential: are either surgically sterile or postmenopausal.

    12. Male patients with female partners of childbearing potential must use highly effective

    methods of birth control during their participation in the study and for a period of 4 months after the last dose of study drug.

    13. Patients must agree to abstain from egg or sperm donation through 7 months for female

    patients and 4 months for male patients after administration of the last dose of study drug.

    14. Ability to adhere to study visit schedule and understand and comply with all protocol

    requirements.

    15. Signed informed consent document indicating that they understand the purpose and

    procedures required for the study and are willing to participate in the study.

You CAN'T join if...

  1. A diagnosis of PH WHO Groups 1, 3, 4, or 5.
  2. Walking activity that is limited by anything other than shortness of breath or fatigue attributed to PH-HFpEF.
  3. Echocardiographic evidence for hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or infiltrative cardiomyopathy
  4. Structural heart repair or replacement of the aortic valve or mitral valve (surgical or percutaneous) within the past 12 months. OR, planned valve intervention in the next 6 months. OR, the presence of echocardiographic findings of significant valve disease as assessed from the qualifying echocardiogram
  5. Any of the following clinical laboratory values within 30 days as specified:
    1. Hemoglobin <10 g/dL
    2. Serum alanine aminotransferase or aspartate aminotransferase levels >3× upper limit of normal (ULN) or total bilirubin >3× ULN.
    3. Electrocardiogram (ECG) with a QTcF >450 msec for males and >470 msec for females at Screening and Baseline in the absence of right bundle branch block.
    4. Platelet count <75,000/mm3.
  6. A diagnosis of pre-existing lung disease
  7. Recent documentation of significant underlying lung disease
  8. Documentation of pulmonary thromboembolism in the last 12 months
  9. Cardiovascular co-morbidities

    10. Receipt of any approved pulmonary arterial hypertension-specific therapies 11. Hospitalization for any indication within 30 days 12. Receipt of any intravenous (IV) inotropes within 30 days 13. Body mass index greater than or equal to 45 kg/m2. 14. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 15. Known history of chronic liver disease 16. Prior exposure to levosimendan 17. Current enrollment in or completion of any other investigational product study within

    30 days of Screening.

    18. Initiation of an exercise program for cardiopulmonary rehabilitation within 45 days 19. History of severe allergic or anaphylactic reaction or hypersensitivity to the

    excipients in the investigational product.

    20. Major surgery within 60 days. Subjects must have completely recovered from any

    previous surgery.

    21. Prior heart, lung, or heart-lung transplants or life expectancy of <12 months 22. Pregnancy or breastfeeding in females 23. History of active malignancy, with the exception of fully treated basal cell

    carcinoma, cervical carcinoma in situ, or squamous cell carcinomas of the skin.

    24. History of clinically significant other diseases that may limit or complicate

    participation in the study.

Locations

  • UCSF- Heart and Vascular Center accepting new patients
    San Francisco California 94143 United States
  • University of Nebraska Medical Center accepting new patients
    Omaha Nebraska 68198 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Tenax Therapeutics, Inc.
ID
NCT05983250
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 152 study participants
Last Updated