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LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF (LEVEL)

Primary Purpose

Pulmonary Hypertension

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
TNX-103
Placebo
Sponsored by
Tenax Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Hypertension focused on measuring HFpEF, Pulmonary hypertension group 2, PH-HFpEF

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Men or women, greater than or equal to18 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 A qualifying Baseline RHC performed within 120 days. The RHC can be a historical RHC done prior to study consent. A qualifying echocardiogram performed within 30 days showing an LVEF greater than or equal to 40% A qualifying 6-MWD of at least 100 meters, but not more than 450 meters at Screening A 48-hour ambulatory cardiac rhythm monitor during the Screening Period to establish the resting heart rate (HR) and rhythm. 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. 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. 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 Female subjects of nonchildbearing potential will be included if they meet the following definition of nonchildbearing potential: are either surgically sterile or postmenopausal. 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. 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. Ability to adhere to study visit schedule and understand and comply with all protocol requirements. Signed informed consent document indicating that they understand the purpose and procedures required for the study and are willing to participate in the study. Exclusion Criteria: A diagnosis of PH WHO Groups 1, 3, 4, or 5. Walking activity that is limited by anything other than shortness of breath or fatigue attributed to PH-HFpEF. 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) 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 Any of the following clinical laboratory values within 30 days as specified: Hemoglobin <10 g/dL per local laboratory. Serum alanine aminotransferase or aspartate aminotransferase levels >3× upper limit of normal (ULN) or total bilirubin >3× ULN. 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. Platelet count <75,000/mm3. A diagnosis of pre-existing lung disease Recent documentation of significant underlying lung disease Documentation of pulmonary thromboembolism in the last 12 months Cardiovascular co-morbidities Receipt of any approved pulmonary arterial hypertension-specific therapies Hospitalization for any indication within 30 days Receipt of any intravenous (IV) inotropes within 30 days Body mass index greater than or equal to 50 kg/m2. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 Known history of chronic liver disease Prior exposure to levosimendan Current enrollment in or completion of any other investigational product study within 30 days of Screening. Initiation of an exercise program for cardiopulmonary rehabilitation within 45 days History of severe allergic or anaphylactic reaction or hypersensitivity to the excipients in the investigational product. Major surgery within 60 days. Subjects must have completely recovered from any previous surgery. Prior heart, lung, or heart-lung transplants or life expectancy of <12 months Pregnancy or breastfeeding in females History of active malignancy, with the exception of fully treated basal cell carcinoma, cervical carcinoma in situ, or squamous cell carcinomas of the skin. History of clinically significant other diseases that may limit or complicate participation in the study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Active Comparator

    Arm Label

    Placebo

    TNX-103

    Arm Description

    Placebo

    levosimendan

    Outcomes

    Primary Outcome Measures

    Six-minute walk distance from Baseline to Week 12

    Secondary Outcome Measures

    KCCQ
    Change in KCCQ - Overall Summary Score
    Clinical Worsening Events
    Change in NT-proBNP
    Decreases in NT-proBNP may indicate an improvement insymptoms
    Change NYHA functional class
    On a scale of I-IV. Lower scores may indicate improvement in symptoms

    Full Information

    First Posted
    August 1, 2023
    Last Updated
    August 30, 2023
    Sponsor
    Tenax Therapeutics, Inc.
    Collaborators
    Medpace, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05983250
    Brief Title
    LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF
    Acronym
    LEVEL
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 2023 (Anticipated)
    Primary Completion Date
    March 2027 (Anticipated)
    Study Completion Date
    July 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Tenax Therapeutics, Inc.
    Collaborators
    Medpace, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief 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).
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pulmonary Hypertension
    Keywords
    HFpEF, Pulmonary hypertension group 2, PH-HFpEF

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    Double blind, randomized, placebo controlled
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    The blind is maintained by the use of a matching placebo.
    Allocation
    Randomized
    Enrollment
    152 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo
    Arm Title
    TNX-103
    Arm Type
    Active Comparator
    Arm Description
    levosimendan
    Intervention Type
    Drug
    Intervention Name(s)
    TNX-103
    Intervention Description
    levosimendan 1 mg
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo
    Primary Outcome Measure Information:
    Title
    Six-minute walk distance from Baseline to Week 12
    Time Frame
    12 weeks
    Secondary Outcome Measure Information:
    Title
    KCCQ
    Description
    Change in KCCQ - Overall Summary Score
    Time Frame
    12 weeks
    Title
    Clinical Worsening Events
    Time Frame
    12 weeks
    Title
    Change in NT-proBNP
    Description
    Decreases in NT-proBNP may indicate an improvement insymptoms
    Time Frame
    12 weeks
    Title
    Change NYHA functional class
    Description
    On a scale of I-IV. Lower scores may indicate improvement in symptoms
    Time Frame
    12 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Men or women, greater than or equal to18 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 A qualifying Baseline RHC performed within 120 days. The RHC can be a historical RHC done prior to study consent. A qualifying echocardiogram performed within 30 days showing an LVEF greater than or equal to 40% A qualifying 6-MWD of at least 100 meters, but not more than 450 meters at Screening A 48-hour ambulatory cardiac rhythm monitor during the Screening Period to establish the resting heart rate (HR) and rhythm. 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. 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. 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 Female subjects of nonchildbearing potential will be included if they meet the following definition of nonchildbearing potential: are either surgically sterile or postmenopausal. 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. 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. Ability to adhere to study visit schedule and understand and comply with all protocol requirements. Signed informed consent document indicating that they understand the purpose and procedures required for the study and are willing to participate in the study. Exclusion Criteria: A diagnosis of PH WHO Groups 1, 3, 4, or 5. Walking activity that is limited by anything other than shortness of breath or fatigue attributed to PH-HFpEF. 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) 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 Any of the following clinical laboratory values within 30 days as specified: Hemoglobin <10 g/dL per local laboratory. Serum alanine aminotransferase or aspartate aminotransferase levels >3× upper limit of normal (ULN) or total bilirubin >3× ULN. 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. Platelet count <75,000/mm3. A diagnosis of pre-existing lung disease Recent documentation of significant underlying lung disease Documentation of pulmonary thromboembolism in the last 12 months Cardiovascular co-morbidities Receipt of any approved pulmonary arterial hypertension-specific therapies Hospitalization for any indication within 30 days Receipt of any intravenous (IV) inotropes within 30 days Body mass index greater than or equal to 50 kg/m2. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 Known history of chronic liver disease Prior exposure to levosimendan Current enrollment in or completion of any other investigational product study within 30 days of Screening. Initiation of an exercise program for cardiopulmonary rehabilitation within 45 days History of severe allergic or anaphylactic reaction or hypersensitivity to the excipients in the investigational product. Major surgery within 60 days. Subjects must have completely recovered from any previous surgery. Prior heart, lung, or heart-lung transplants or life expectancy of <12 months Pregnancy or breastfeeding in females History of active malignancy, with the exception of fully treated basal cell carcinoma, cervical carcinoma in situ, or squamous cell carcinomas of the skin. History of clinically significant other diseases that may limit or complicate participation in the study.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Kevin Crawford
    Phone
    19198552145
    Email
    k.crawford@tenaxthera.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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