Heart Failure study with Danicamtiv in patients with reduced heart function caused by gene mutation.

Phase 1

• Conditions: Primary Dilated Cardiomyopathy Due to Either MYH7 or TTN Variants.; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2019-003626-24-DE
• Lead Sponsor: MyoKardia Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-01-08
• Last Update Posted: 30 January 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Participants must complete Part A before opting in and starting Part B.
Part A:
I1.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.
I2. Men or women 18 to 80 years of age (inclusive) at the Screening visit.
I3. For MYH7 and TTN cohorts, diagnosis of primary DCM, clinically stable and associated with probably disease-causing variant MYH7 or TTN as defined by (a) through (f) of the following, All study participants, regardless of the cohort, must meet (g) and (h) criteria:
a. Primary DCM participants that have no identified etiology other than variant in MYH7 or TTN as determined by the Investigator. Participants with a diagnosis of heart failure with reduced ejection
fraction should be on Guideline Directed Medical Therapy as tolerated.
b. Pathogenic or likely pathogenic variants submitted in the form of final official genetic laboratory reports will be reviewed centrally by the Sponsor and coordinating investigator for eligibility. Some variants designated VUS may also be permitted upon central review.
c. DCM is not secondary to long-standing MYH7 or TTN-related HCM or left ventricular noncompaction cardiomyopathy, as determined by the Investigator.
d. Participants with DCM related to pathogenic or likely pathogenic variants of TTN must not also have a diagnosis of peripartum DCM (DCM diagnosed initially in the last month of pregnancy or the 6 months following delivery).
e. In participants with DCM related to pathogenic or likely pathogenic variants of TTN, DCM must not be secondary to significant exposure to cardiotoxic chemotherapy agents as determined by the investigator.
f. In participants with DCM related to pathogenic or likely pathogenic variants of TTN, DCM must not be due to a history of significant alcohol abuse as determined by the investigator.
g. Documented left ventricular ejection fraction (LVEF) 15-45% (on 2 occasions), including at least once during Screening and confirmed by the Echo Core Laboratory.
If a participant's most recent prior TTE (within past 12 months) documents a LVEF =45%, then only a single screening visit confirming LVEF =45% by the Echo Core Laboratory is required.
If no prior documented LVEF =45% by TTE within the past 12 months is available, then 2 screening TTEs are needed at least one week (7 days) apart.
In addition, the absolute difference between the 2 LVEF values qualifying the participant should be <12%.
h. Participant receives chronic medication for the treatment of heart failure reflecting current guidelines, including at least one of the following, unless not tolerated or contraindicated: ß-blocker, angiotensin converting enzyme inhibitor, angiotensin receptor blocker, or angiotensin receptor neprilysin inhibitor. Such treatments should have been given at stable doses for = 2 weeks with no plan to modify during the study.
I4. Sinus rhythm or stable atrial or ventricular pacing or persistent atrial fibrillation that is adequately rate-controlled to allow PD assessments by TTE.
I5. If multiple members of a family meet eligibility criteria, a maximum of 3 eligible participants per family may enroll in the study.
I6. Female participants of childbearing potential (Appendix 6) must not be pregnant or lactating and, if sexually active, must use one of the following highly-effective birth control metho

Exclusion Criteria

Part A:
E1. Inadequate echocardiographic acoustic windows.
E2. A participants has a QTcF interval >480 msec, not attributable to ventricular pacing or has prolonged QRS duration = 120 msec, average of triplicate electrocardiograms (ECG).
E3. a. For MYH7 and TTN cohorts, participants with known pathogenic variant of another gene implicated in DCM at screening
b. For the cohort of participants with primary DCM due to other causalities than MYH7 and TTN, known in MYH7 or TTN variants implicated in DCM at Screening.
E4. HFrEF considered to be caused primarily by ischemic heart disease, chronic valvulopathy, or another condition, as determined by the Investigator.
E5. Recent (< 90 days) acute coronary syndrome or angina pectoris.
E6. Coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft) within prior 90 days.
E7. Recent (< 90 days) hospitalization for heart failure, use of intravenous diuretic or chronic intravenous inotropic therapy or other cardiovascular event (eg, cerebrovascular accident).
E8. Known aortic stenosis of moderate or greater severity.
E9. Presence of disqualifying cardiac rhythms that would preclude echocardiographic assessments, as determined by the Investigator, including: (a) rapid, inadequately rate-controlled atrial fibrillation or (b) frequent premature ventricular contractions that might interfere with reliable echocardiographic measurements of left ventricular function.
E10. Hypersensitivity to danicamtiv or any of the components of the danicamtiv formulation.
E11. Active infection, indicated clinically as determined by the investigator. In the case of SARS-CoV-2 (COVID-19) infection within 4 weeks prior to and during Screening, symptoms must have completely resolved and based on Investigator assessment in consultation with the Clinical Trial Physician, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment. The methods to assess SARS-CoV-2 (COVID-19) infection include PCR, antigen test and serology tests. Each study site should follow requirements per local institutional or regulatory guidance if any.
E12. 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.
E13. 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]).
E14. Serum potassium < 3.5 or > 5.5 mEq/L.
E15. Any persistent (2 or more) out-of-range laboratory parameters (chemistry, hematology) at Screening, considered by the investigator and the medical monitor to be clinically significant.
E16. History or evidence of any other clinically significant disorder, condition, or disease (including substance abuse) that, in the opinion of the investigator or the Sponsor Physician would pose a risk to participant safety or interfere with the study evaluation, procedures, completion, or lead to premature withdrawal from the study.
E17. A life expectancy of < 6 months.
Prior/Concurrent Clinical Study Experience:
E18. Participated in a clinical trial in which the participant received any investigational drug (or is currently using an investigational device) within 30 days prior to Screening, or at least 5 times

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified