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    Summary
    EudraCT Number:2016-000126-19
    Sponsor's Protocol Code Number:SPIHF-204
    National Competent Authority:Latvia - SAM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-07-25
    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 ConcernedLatvia - SAM
    A.2EudraCT number2016-000126-19
    A.3Full title of the trial
    A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Cardiac and Renal Effects of Short Term Treatment with Elamipretide in Patients Hospitalized with Congestion due to Heart Failure
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to Evaluate the Effect on the Heart and Kidneys of Short Term Treatment with Elamipretide in Patients Hospitalized with Congestion due to Heart Failure
    A.4.1Sponsor's protocol code numberSPIHF-204
    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 SponsorStealth BioTherapeutics Inc.
    B.1.3.4CountrySwitzerland
    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 supportStealth BioTherapeutics Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationStealth BioTherapeutics Inc.
    B.5.2Functional name of contact pointMatthew Millstein
    B.5.3 Address:
    B.5.3.1Street Address275 Grove Street, Suite 3-107
    B.5.3.2Town/ cityNewton, MA
    B.5.3.3Post code02466
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 617 762.2539
    B.5.5Fax number+1 508 733.7777
    B.5.6E-mailMatthew.Millstein@stealthbt.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 nameElamipretide
    D.3.2Product code MTP-131
    D.3.4Pharmaceutical form Powder and solution for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNelamipretide
    D.3.9.1CAS number 736992-21-5
    D.3.9.2Current sponsor codeMTP-131
    D.3.9.3Other descriptive nameBENDAVIA™, MTP-131, SS-31, SPI-31, SBT-31
    D.3.9.4EV Substance CodeSUB79599
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 placeboPowder for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Congestive heart failure
    E.1.1.1Medical condition in easily understood language
    Heart failure occurs when the heart muscle is weakened and cannot pump enough blood to meet the body's needs for blood and oxygen
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10010684
    E.1.2Term Congestive heart failure
    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 ability of elamipretide compared to placebo to improve cardiac function measured by a reduction in N-terminal pro-brain natriuretic peptide (NT-proBNP) up to Day 8 (or at discharge if earlier) in patients hospitalized with congestion due to heart failure
    E.2.2Secondary objectives of the trial
    _To evaluate the effect of elamipretide on changes between baseline and both Day 3 and Day8/Earlier Discharge on:
    o renal function (eGFR as per MDRD)
    o body weight
    o body weight per mg of furosemide administered
    _ Clinical status (e.g patients and physician global assessment and treatment failures) at Day 3 and Day 8
    _The average daily dose of diuretic (furosemide – adjusted for thiazide dose if administered) between baseline and Day 3 and Day 8/Early Discharge
    _The safety and tolerability of elamipretide
    _The plasma pharmacokinetics (PK) of elamipretide, its metabolites, and furosemide following a single dose and multiple doses of elamipretide in a selected number of
    patients
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Willing and able to provide signed informed consent form (ICF) prior to participation in any study-related procedures
    2. Aged ≥18 years
    3. history of chronic heart failure for at least 1 month
    4. Treated with ≥40 mg/day of furosemide or bumetanide ≥1 mg/day or torasemide ≥10 mg/day for at least 1 month
    5. In-hospital observation/admission and treatment for ≤72 hours and primary cause for admission is heart failure with persistent congestion in the opinion of the Investigator (i.e.
    at least +2 pitting oedema and/or an estimated 8 kg gain in weight over baseline over the past 4 weeks) requiring intravenous loop diuretic therapy
    6. Able to be weighed
    7. Sufficiently severe oedema to justify treatment by an intravenous infusion of furosemide of 10 mg/hour for at least 48 hours
    8. Systolic blood pressure ≥ 90 mmHg and considered to be haemodynamically stable, in the opinion of the Investigator
    9. History of left ventricular ejection fraction (LVEF) ≤40% confirmed in the last 18 months
    10. NT-proBNP >1500 pg/ml or BNP >500 pg/ml
    11. An eGFR of ≥30mL/min/1.73 m2 using the MDRD study equation
    12. Women of childbearing potential must agree to use 1 of the following methods of birth control from the date they sign the ICF until two months after the last dose of study drug:
    a. Abstinence, when it is in line with the preferred and usual lifestyle of the subject. Subject agrees to use an acceptable method of contraception should they become sexually active
    b. Maintenance of a relationship with a male partner who has been surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days prior to the Screening Visit or confirmed via sperm analysis)
    c. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream AND either hormonal contraception (oral, implanted, or injectable) or an intrauterine device or system
    13. Willing to adhere to the study requirements for the length of the trial
    E.4Principal exclusion criteria
    1. Completely bedridden for >2 weeks prior to admission. Patients should at least have been able to go the toilet and back and to get out of bed for meals at some time during this
    period
    2. Known intolerance of furosemide
    3. Acute coronary syndrome, stroke, or transient ischemic attack (TIA), coronary or peripheral revascularization procedures, valve procedures, OR any major surgical procedure within the previous 6 weeks
    4. Invasive cardiac investigation and/or treatment (i.e. coronary angiography, percutaneous coronary intervention [PCI] or surgery) or other surgical procedure planned in the next 4 weeks
    5. Use of intravenous radiographic contrast agent within 72 hours prior to screening or planned use during the study
    6. Severe, in the investigators opinion, uncorrected valve disease or congenital heart disease as the cause for cardiac decompensation
    7. Acute mechanical cause of decompensated heart failure such as papillary muscle rupture
    8. Obstructive or infiltrative cardiomyopathy (e.g. amyloid, sarcoid, etc), suspected acute myocarditis, or heart failure related to an untreated metabolic condition (e.g. haemochromatosis)
    9. Second or third degree heart block unless the subject has a ventricular pacemaker
    10. Atrial fibrillation/flutter with sustained ventricular response of >130 bpm
    11. Placement of a ventricular resynchronization device within the previous 6 weeks
    12. Treatment or planned treatment with intravenous inotropic agents other than digoxin at any time on this admission
    13. Receipt of intravenous vasodilator therapy ≤ 6 hours prior to randomization
    14. The presence of any mechanical assist device or listed for or a history of a heart transplant
    15. Suspected systemic infection or pneumonia and/or the need for antibiotic treatment between admission and time of consent. Patients given antibiotics without clear justification can be included as long as it is appropriate to discontinue the antibiotics
    16. Severe respiratory disease or anticipated need for mechanical respiratory support (i.e. mechanical ventilation)
    17. Anuric in the previous 24 hours
    18. Haemoglobin <9 g/dL at screening or planned blood transfusions in the next 30 days
    19. Serum potassium >5.5 mEq/L
    20. Marked proteinuria suggestive of nephrotic syndrome
    21. Estimated GFR (eGFR) as per MDRD equation <30 ml/min
    22. Serum albumin of < 2.8 g/dL
    23. Liver enzymes (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) elevation >5 times the upper limit of normal (ULN)
    24. Total bilirubin >2.0 times ULN in the absence of Gilbert’s Syndrome
    25. Known active hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection, or diagnosis of immunodeficiency
    26. Known active drug or alcohol abuse within 1 year of the Screening Visit at the discretion of the Investigator (i.e. 15 or more drinks for men per week or 8 or more for women).
    27. Currently receiving treatment with chemotherapeutic agents or immunosuppressant agents or having received prior radiation therapy to the chest
    28. Current or planned ultrafiltration, paracentesis, haemofiltration or dialysis
    29. Currently receiving treatment of any intravenous steroid or > 5 mg of oral prednisone (or equivalent)
    30. Recipient of stem cell or gene therapy or current therapeutic investigational devices
    31. Participation in another clinical trial with an investigative product within 3 months prior to the Screening Visit
    32. Any significant acute or chronic medical or psychiatric illness or social situation that, in the judgment of the Investigator, could compromise a subject’s safety, limit subject’s ability to complete the study and follow-up period, and/or compromise the objectives of the study
    33. Women who are pregnant, planning to become pregnant, or lactating
    34. Currently receiving treatment with therapeutic doses of any of the novel or direct oral anticoagulants (vitamin K antagonist are permitted)
    35. Currently receiving treatment with sacubitril (Entresto™)
    36. Hypersensitivity to elamipretide or any of its excipients
    E.5 End points
    E.5.1Primary end point(s)
    Change in NT-proBNP between Baseline and Day 8/Early Discharge
    E.5.1.1Timepoint(s) of evaluation of this end point
    At Day 8 or early discharge
    E.5.2Secondary end point(s)
    _Clinical Improvement
    a. Renal function (eGFR as per MDRD)
    b. Body weight
    c. Body weight per mg of furosemide administered
    d. Clinical status (e.g. patients and physician global assessment and treatment failures)
    e. The average dose of diuretic (furosemide – adjusted for thiazide dose if administered)
    _The plasma pharmacokinetics (PK) of elamipretide, its metabolites, and furosemide following a single dose and multiple doses of elamipretide in a selected number of patients
    _Pharmacokinetics
    The following plasma PK parameters will be determined for elamipretide (MTP-131), its metabolites (M1 and M2), and furosemide where possible and appropriate:
    Day 1: Cmax, Tmax, AUC(0-last), AUC(0-inf), AUC%extrap, t½, Cl, Vd, MRT
    Day 7: Cmin,ss, Cmax,ss, Tmax, AUC(0-tau),ss, AUC(0-last), AUC(0-inf), AUC%extrap, t½, Vd
    Additional Parameters: Cmax, Cmin on Days 2 - 6, P/T fluctuation (%) under steady state conditions, accumulation ratio for Cmax and AUC(0-tau)
    _ Treatment failures will be defined as any of the following criteria, should they occur before the assessment on Day 8/Early Discharge:
    a. Cardiovascular Death
    b. The need to increase the dose of IV furosemide to >10 mg/hour or equivalent
    c. The need to add new therapy or increase therapy of a thiazide or thiazide-like diuretic to a loop diuretic
    d. The need for intravenous inotropic agents (not including digoxin)
    e. The need for mechanical circulatory support
    f. The need for intubation and mechanical ventilation
    g. The need for renal replacement therapy or ultrafiltration
    h. Not medically fit for discharge at Safety Follow-Up Visit
    E.5.2.1Timepoint(s) of evaluation of this end point
    All secondary efficacy endpoints will assess changes from baseline to Day 3 and Day 8 or Early Discharge
    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 Yes
    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 No
    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 trial2
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA55
    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
    Belgium
    France
    Hungary
    Italy
    Latvia
    Netherlands
    Poland
    Serbia
    Spain
    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 years1
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 200
    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 state32
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 260
    F.4.2.2In the whole clinical trial 300
    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)
    all subjects will go on standard care specified by the responsible 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 Decision2016-08-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-27
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-12-27
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