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    Summary
    EudraCT Number:2017-005093-19
    Sponsor's Protocol Code Number:AT251-G-17-005
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-12-06
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2017-005093-19
    A.3Full title of the trial
    A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of JTT-251 Administered for 24 Weeks to Participants with Heart Failure with Reduced Ejection Fraction
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate the efficacy and safety of an oral investigational drug JTT-251, in patients with heart failure with reduced ejection fraction.
    A.3.2Name or abbreviated title of the trial where available
    BEAT-CHF
    A.4.1Sponsor's protocol code numberAT251-G-17-005
    A.5.4Other Identifiers
    Name:US IND Number Number:137287
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAkros Pharma Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAkros Pharma Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAkros Pharma Inc.
    B.5.2Functional name of contact pointKala Patel
    B.5.3 Address:
    B.5.3.1Street Address302 Carnegie Center, Suite 300
    B.5.3.2Town/ cityPrinceton
    B.5.3.3Post code NJ 08540
    B.5.3.4CountryUnited States
    B.5.4Telephone number+16099196131
    B.5.5Fax number+16099199575
    B.5.6E-mailpatel@akrospharma.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameJTT-251 monohydrate
    D.3.2Product code JTT-251
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot available
    D.3.9.2Current sponsor codeJTT-251
    D.3.9.3Other descriptive nameJTT-251 MONOHYDRATE
    D.3.9.4EV Substance CodeSUB191298
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameJTT-251 monohydrate
    D.3.2Product code JTT-251
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot available
    D.3.9.2Current sponsor codeJTT-251
    D.3.9.3Other descriptive nameJTT-251 MONOHYDRATE
    D.3.9.4EV Substance CodeSUB191298
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Heart Failure with Reduced Ejection Fraction (HFrEF)
    E.1.1.1Medical condition in easily understood language
    HFrEF or systolic (it's phase of the heartbeat when the heart pumps out the blood) heart failure is a condition where the left ventricle doesn't pump blood out to the body as normal during a systole.
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10078289
    E.1.2Term Heart failure with reduced ejection fraction
    E.1.2System Organ Class 100000004849
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To evaluate the efficacy of JTT-251 in participants with Heart Failure with Reduced Ejection Fraction (HFrEF)
    - To evaluate the safety and tolerability of JTT-251 following administration for 24 weeks in participants with HFrEF
    - To evaluate the exposure-response of the efficacy and safety of JTT-251 in participants with HFrEF
    - To evaluate the PK of JTT-251 in participants with HFrEF
    E.2.2Secondary objectives of the trial
    Not Applicable
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    To qualify for the study, the participant must satisfy the following criteria:
    1. Male or female, age 18 to 85 years (inclusive), at the Screening Visit;
    2. Participants with a clinical diagnosis of symptomatic HF ≥3 months prior to the Screening Visit;
    3. Participants with NYHA functional class II or III at the Screening Visit;
    4. Participants must be on stable, guideline-directed medical therapy for HF, consistent with AHA, ACC, HFSA or ESC guidelines for at least 30 days prior to the Screening Visit. These therapies include an ACEI or ARB with/without a neprilysin inhibitor, in combination with an evidence-based β-blocker and a MRA, in appropriate participants
    5. Participants must have a documented history of LVEF ≤35% within 6 months prior to the Screening Visit using any of the following modalities: echocardiography, single-photon emission computed tomography (SPECT), multigated acquisition (MUGA), computed tomography (CT) scanning, magnetic resonance imaging (MRI) or ventricular angiography; if more than one measurement was performed, then the most recent one should be used for eligibility;
    Note: If LVEF measurement was obtained >6 months prior to the Screening Visit, a local echocardiography measurement and interpretation will be used to determine eligibility (i.e., LVEF ≤35%).
    6. Participants with a plasma NT-pro-BNP level ≥900 pg/mL at the Screening Visit;
    7. Females may participate if they meet one of the following criteria:
    • surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or
    • post-menopausal, as defined by permanent cessation of menstruation for ≥12 months without an alternative medical cause at the Screening Visit.
    a. practice abstinence, or
    b. have same-sex partner, and not planning a pregnancy, or
    c. use one highly effective contraceptive method of birth control, which includes intrauterine devices, male partner sterilization (at least six months prior to screening with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate, and the vasectomized male partner should be the sole partner for that participant), tubal ligation, intrauterine hormone-releasing systems, or
    d. use a double-barrier method of birth control, which includes a combination of male condom with either diaphragm, cervical cap or vaginal sponge, all with spermicide.
    All other females will be considered of childbearing potential and must either:
    Note: Periodic abstinence (calendar, symptothermal, post ovulation
    methods), withdrawal (coitus interruptus), spermicides only, and
    concomitant use of a female and male condom are not acceptable
    methods of contraception.
    8. Males must either practice sexual abstinence, have same-sex partner, use a barrier contraceptive method with spermicide (for the duration of the treatment period and until 28 days after the last dose of study drug), or be sterilized at least six months prior to screening (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
    Notes: Males who are sterile or who have sterile or post-menopausal female partners are not required to use contraception if said female partner is the sole partner for that participant. Males must not donate sperm for the duration of the study and for 28 days after the last dose of study drug.
    If the female partner is of childbearing potential, she must agree to use
    at least one of the acceptable forms of birth control listed above (in
    addition to the method utilized by the male subject) for the duration of
    the study and for at least 28 days after the participant takes the last
    dose of study drug.
    9. Able and willing to give written informed consent.
    E.4Principal exclusion criteria
    The following criteria will exclude a participant from participating in the study:
    1. Participants with confirmed acute MI (i.e., Type 1) within 30 days prior to the Screening Visit or unstable angina, a history of coronary revascularization (percutaneous coronary intervention and/or coronary artery bypass grafting) or other cardiovascular surgery within 90 days prior to the Screening Visit;
    2. Participants whose HF is due to congenital heart disease, active myocarditis or constrictive pericarditis;
    3. Participants who have received a heart transplant or are on a transplant list or who have a history of LV assist device implantation;
    4. Participants with severe stenotic valvular disease or severe outflow tract obstruction;
    5. Participants with a history of stroke or cerebral transient ischemic attack within 30 days prior to the Screening Visit;
    6. Participants who started cardiac resynchronization therapy within 90 days prior to the Screening Visit;
    Note: Implantable cardioverter defibrillator (ICD) placement alone or generator change is acceptable.
    7. Participants with planned cardiovascular surgery and/or cardiac resynchronization therapy during the double-blind treatment period;
    8. Participants who were admitted to hospital for HF within 30 days prior to Visit 2;
    9. Participants with known active liver disease or with aminotransferases (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) >3.0x upper limit of normal (ULN) or total bilirubin >1.5x ULN at the time of screening;
    Note: Participants with documented benign liver condition that can result in elevated bilirubin levels (e.g., Gilbert’s Syndrome) are eligible to participate in the study.
    10. Participants unable to perform a six minute walk distance (6MWD) test at Visit 2;
    11. Participants with resting symptomatic hypotension or uncontrolled hypertension (i.e., systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg) at the Screening Visit;
    12. Participants with clinically significant chronic renal insufficiency (i.e., estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2 using the 4-variable Modification of Diet in Renal Disease [MDRD] formula) or who are on or indicated to start renal dialysis within the next 90 days;
    eGFR (in mL/min/1.73 m2) = 175 × Serum Creatinine -1.154 × age -0.203 × 1.212 (for black participant) × 0.742 (for female participant)
    13. Diabetic participants with hemoglobin A1c (HbA1c) >10% measured at the Screening Visit;
    14. Participants with hemoglobin <8 g/dL at the Screening Visit;
    15. Participants currently receiving or have received an investigational product (including an investigational drug or other investigational therapeutic intervention) within 28 days, five half-lives or twice the duration of the biological effect of the investigational product, if known (whichever is longer) prior to the Screening Visit;
    16. Participants with a history of recreational drug abuse within six months of the Screening Visit;
    Note: Medical marijuana prescribed by a physician is acceptable.
    17. Participants with a history of alcohol abuse within six months of the Screening Visit;
    18. Participants with an ANC <1200/μL at the Screening Visit;
    19. Participants with systemic effects of untreated active infection(s) (e.g., fever ≥100.4°F [38.0°C]) at Visit 2;
    Note: Participants with successfully treated infections or infections that required antibiotics will be permitted if resolved >7 days prior to Visit 2.
    20. Participants who test positive for human immunodeficiency virus (HIV) antibodies at the Screening Visit;
    21. Participants with current malignancies or who are receiving or require active cancer treatment (exceptions include adequately treated or excised non-metastatic basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ);
    22. Participants who have unstable physical or major psychiatric conditions (e.g., schizophrenia, clinically unstable major psychiatric disorder) that would put the participant at risk, or would interfere with study procedures according to the Investigator’s clinical judgement;
    23. Females who are pregnant as determined by a positive serum human chorionic gonadotropin (hCG) test result at the Screening Visit or urine hCG at Visit 2;
    Note: Any positive urine pregnancy test result at Visit 2 must be verified with a serum pregnancy test prior to randomization.
    24. Females who are lactating at the Screening Visit or at Visit 2;
    25. Participants who are unwilling or unable to comply with the requirements of the study.
    E.5 End points
    E.5.1Primary end point(s)
    • Change from baseline to end of treatment (EOT) in:
    - Left ventricular ejection fraction (LVEF), Left ventricular end systolic volume (LVESV) index and Left ventricular end diastolic volume (LVEDV) index as assessed by two-dimensional echocardiography (2D-echo)
    - NT-pro-BNP
    - 6MWD test
    - NYHA functional class
    • JTT-251 trough plasma levels at Weeks 4, 12 and 24 and JTT-251 plasma concentrations (post-dose) at Week 4
    • Relationship between JTT-251 exposure and efficacy, and safety parameters
    • Safety
    - Number of participants with adverse events (AEs), type and severity of AEs
    - Change from baseline in safety laboratory, vital sign and electrocardiogram (ECG) parameters
    - AEs leading to permanent discontinuation of study drug.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 0, 1, 2, 4, 8, 12, 16, 20, 24, 28
    E.5.2Secondary end point(s)
    • Change from baseline to EOT in:
    - Supplementary cardiac function estimates as determined by echocardiography
    - Health-related quality of life (QoL) assessment as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ)
    - HbA1c and fasting plasma glucose
    - Branched-chain amino acids (BCAAs), alanine, pyruvic and lactic acid
    - Cardiac troponin I, suppression of tumorigenicity 2 (ST2) and galectin 3
    - eGFR and cystatin C
    - Albumin-to-creatinine ratio (ACR)
    - Serum myostatin and brain-derived neurotrophic factor (BDNF)
    • All deaths (cardiovascular or non-cardiovascular) and cardiovascular hospitalizations up to Week 28 as defined in the Clinical Events Committee (CEC) charter
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 0, 1, 2, 4, 8, 12, 16, 20, 24, 28
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA58
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Chile
    Denmark
    Germany
    Hungary
    Israel
    Netherlands
    Poland
    Romania
    Russian Federation
    Serbia
    Ukraine
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months9
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 120
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 280
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 284
    F.4.2.2In the whole clinical trial 400
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Post study participation, the subject will be released into local standard of care as advised by treating physician.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-12-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-02-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-04-29
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