Heart Failure study in patients with reduced heart function.
- Conditions
- Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]Heart Failure with Reduced Ejection Fraction
- Registration Number
- EUCTR2018-002239-11-PL
- Lead Sponsor
- MyoKardia Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 56
1. Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent according to federal, local, and institutional guidelines before the first study-specific procedure.
2. Men or women 18 to 80 years of age at the Screening visit.
3. Body mass index (BMI) 18 to 40 kg/m2, inclusive, at the Screening visit and all required assessments can be reliably performed.
4. Sinus rhythm or stable atrial pacing with mean resting heart rate (HR) 50-95 beats per minute (bpm), inclusive. (Patient will be ineligible to dose if, on Day 1, the predose HR measurement is = 95 bpm. Heart rate is the mean of 3 measurements taken 1 minute apart. A single measurement would not make a patient ineligible).
5. Has stable, chronic HFrEF of moderate severity as defined by all of the
following:
• For the first 3 patients in each multiple-ascending dose (MAD) cohort
testing a new (higher) daily dose: documented LVEF 25% to 35% during
Screening (as confirmed by ECHO Central Lab).
• For other patients in the MAD Cohorts (and all patients in SAD
Cohorts): documented LVEF 15% to 35% during Screening (as confirmed
by ECHO Central Lab).
• LVEF must be confirmed with second screening ECHO to be performed at least 7 days after initial screening ECHO. Results of both must meet
inclusion criteria and must be received from core lab prior to dosing. In the event of extended screening windows due to SRC reviews, effort
should be made to ensure second ECHO is near planned time of randomization.
• Chronic medication for the treatment of heart failure consistent with current guidelines that has been given at stable doses for = 2 weeks with no plan to modify during the study. This includes treatment with at least one of the following unless not tolerated or contraindicated: betablocker, angiotensin converting enzyme (ACE) inhibitor/angiotensin
receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI).
6. Female patients must not be pregnant or lactating. Male patients (including men who have had vasectomies), as there may be a risk of drug being secreted in the ejaculate, should use barrier methods for the duration of the study and for 3 months after the last dose of study medication. All patients, if sexually active, must be using one of the following highly-effective birth control methods from the Screening visit through 3 months after the last dose of investigational medicinal product (IMP):
• Hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), or intrauterine hormone-release system (IUS) plus barrier (eg, male using condom or female using diaphragm or cervical cap).
• Vasectomy plus barrier.
• Female is surgically sterile for 6 months or postmenopausal for 1 year. Permanent sterilization includes hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and/or documented bilateral tubal occlusion at least 6 months prior to Screening. Females are considered postmenopausal if they have had amenorrhea for at least 1 year or more following cessation of all exogenous hormonal treatments, and follicle-stimulating hormone (FSH) levels are in the postmenopausal range.
• Male patients with postmenopausal partners.
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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
1. Inadequate echocardiographic acoustic windows.
2. Any of the following ECG abnormalities (a) QTcF > 480 ms (Fridericia’s correction, not attributable to pacing or prolonged QRS duration, average of triplicate Screening ECGs) or (b) second-degree atrioventricular block type II or higher in a patient who has no pacemaker.
3. Hypersensitivity to MYK-491 or any of the components of the MYK-491 formulation.
4. Active infection as indicated clinically as determined by the investigator.
5. History of malignancy of any type within 5 years prior to Screening, with the exception of the following surgically excised cancers occurring more than 2 years prior to Screening: in situ cervical cancer, nonmelanomatous skin cancers, ductal carcinoma in situ, and nonmetastatic prostate cancer.
6. Positive serologic test at Screening for infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
7. Hepatic impairment (defined as alanine aminotransferase [ALT]/ aspartate aminotransferase [AST] > 3 times upper limit of normal [ULN] and/or total bilirubin [TBL] > 2 times ULN).
8. Severe renal insufficiency (defined as current estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m2 by simplified Modification of Diet in Renal Disease equation [sMDRD]).
9. Serum potassium < 3.5 or > 5.5 mEq/L.
10. Any persistent out-of-range safety laboratory parameters (chemistry, hematology, urinalysis), considered by the investigator and medical monitor to be clinically significant.
11. History or evidence of any other clinically significant disorder, condition, or disease (including substance abuse) that, in the opinion of the investigator or MyoKardia physician would pose a risk to patient safety or interfere with the study evaluation, procedures, completion, or lead to premature withdrawal from the study.
12. Participated in a clinical trial in which the patient received any investigational drug (or is currently using an investigational device) within 30 days prior to Screening, or at least 5 times the respective elimination half-life (whichever is longer).
13. Previous participation in a clinical trial with MYK-491, with the
exception that patients that participated or were screen failures in one part of this trial may participate in the other part, ie patients may enroll in Part 1 (SAD) followed by Part 2 (MAD) or Part 2 (MAD) followed by
Part 1 (SAD), with the following caveats:
• If the patient has an ongoing adverse event (AE), has had a serious
adverse event (SAE), or has met any stopping criteria, the investigator should contact the Sponsor prior to enrolling the patient in a subsequent cohort.
• Patients must have at least 1 week washout after the end of MAD
dosing prior to SAD dosing, or at the end of SAD dosing prior to MAD
dosing.
• Patients do not need to rescreen if MAD screening occurred within 12 weeks of the first SAD dosing, or if SAD screening occurred within 12 weeks of the first MAD dosing. Investigators should verify that patients are clinically stable and no exclusions have occurred during the interim; if > 12 weeks have elapsed or there is clinical instability, then patients should be rescreened.
14. Unable to comply with the study restrictions/requirements, including, in particular, the number of required overnight stays at the clinical site.
15. Is employed by, or is a first-degree relative of someone employed by, MyoKardia or Sanofi, the investigator, or his/her staff or family.
1
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method