Congestive heart failure MedDRA version: 19.0 Level: LLT Classification code 10010684 Term: Congestive heart failure System Organ Class: 100000004849
Conditions
Interventions
Product Name: Elamipretide
Product Code: MTP-131
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: elamipretide
CAS Number: 736992-21-5
Current Sponsor code: MTP
Sponsors
Stealth BioTherapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
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 5.5 mEq/L 20. Marked proteinuria suggestive of nephrotic syndrome 21. Estimated GFR (eGFR) as per MDRD equation 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 medica
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: _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;Primary end point(s): Change in NT-proBNP between Baseline and Day 8/Early Discharge;Timepoint(s) of evaluation of this end point: At Day 8 or early discharge | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(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;Secondary 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 | — |
Countries
Belgium, Bulgaria, France, Hungary, Italy, Latvia, Netherlands, Poland, Serbia, Spain, United Kingdom
Contacts
Public ContactMatthew Millstein
Stealth BioTherapeutics Inc.
Outcome results
None listed