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Heart Failure study with Danicamtiv in patients with reduced heart function caused by gene mutation
EU CTIS ID: 2023-505492-68-00
What this study is testing
To establish preliminary safety and tolerability of treatment with danicamtiv in participants with myosin heavy chain 7 (MYH7) dilated cardiomyopathy (DCM) or titin (TTN)-DCM, or DCM by other causalities for Part A
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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
- I3_(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.
- I3_(c). DCM is not secondary to long-standing MYH7 or TTN-related hypertrophic cardiomyopathy (HCM) or left ventricle noncompaction cardiomyopathy, as determined by the Investigator.
- I3_(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).
- I3_(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.
- I3_(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
You likely can't join if
- Part A_E1. Inadequate echocardiographic acoustic windows.
- Part A_E18. Prior/Concurrent Clinical Study Experience: 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 the respective elimination half-life (whichever is longer).
- Part A_E19. WOCBP with a positive pregnancy test
- Part A_E10. Hypersensitivity to danicamtiv or any of the components of the danicamtiv formulation
- Part A_E20. Is employed by or is a first-degree relative of someone employed by the Sponsor, the investigator, or his/her staff or family
- Part A_E21. Currently placed in hospital or facility due to legal or administrative order
See the full eligibility criteria
Who can join
- 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
- I3_(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.
- I3_(c). DCM is not secondary to long-standing MYH7 or TTN-related hypertrophic cardiomyopathy (HCM) or left ventricle noncompaction cardiomyopathy, as determined by the Investigator.
- I3_(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).
- I3_(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.
- I3_(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
- Part A_I7. Male participants must use barrier method of contraception (whether or not the participant had vasectomy)
- Part A_I8. I8. For the cohort of primary DCM due to other causalities than MYH7 and TTN, participant must meet the following criteria in addition to I1, I2, I3 (g) and (h), I4, I5, I6, and I7. a. The cause of DCM is not related to MYH7 or TTN variants b. The cause of primary DCM is by variants of the other genes except MYH7 and TTN, or non-genetic cause.
- I3_(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 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 subject should <12%.
- I3_(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: β-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
- Part A_I4. Sinus rhythm or stable atrial or ventricular pacing or persistent atrial fibrillation that is adequately rate-controlled to allow PD assessments by TTE.
- Part A_I5. If multiple members of a family meet eligibility criteria, a maximum of 3 eligible subjects per family may enroll in the study
- Part A_I6. Female of childbearing potential (Appendix 6) must not be pregnant or lactating and, if sexually active, must use one of the following highlyeffective birth control methods from the Screening visit through 3 months after the last dose of study drug: -combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation or progestogenonly hormonal contraception associated with inhibition of ovulation by oral, implantable, or injectable route of administration -intrauterine device (IUD) -intrauterine system (IUS)-Female participant is surgically sterile (includes documented hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and/or bilateral tubal occlusion or ligation prior to Screening). -Female participant postmenopausal for 1 year - 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 partners of female participants must also use a contraceptive (eg, barrier, condom, or vasectomy)
- Part A_I2. Men or women 18 to 80 years of age (inclusive) at the Screening visit.
- Part A_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
- I3_(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.
What rules you out
- Part A_E1. Inadequate echocardiographic acoustic windows.
- Part A_E18. Prior/Concurrent Clinical Study Experience: 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 the respective elimination half-life (whichever is longer).
- Part A_E19. WOCBP with a positive pregnancy test
- Part A_E10. Hypersensitivity to danicamtiv or any of the components of the danicamtiv formulation
- Part A_E20. Is employed by or is a first-degree relative of someone employed by the Sponsor, the investigator, or his/her staff or family
- Part A_E21. Currently placed in hospital or facility due to legal or administrative order
- Part A_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.
- Part A_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
- Part A_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])
- Part A_E14. Serum potassium < 3.5 or > 5.5 mEq/L
- Part A_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.
- Part A_E4. HFrEF considered to be caused primarily by ischemic heart disease, chronic valvulopathy, or another condition, as determined by the Investigator
- Part A_E2. A participant has a QTcF interval > 480 msec (not attributable to ventricular pacing or prolonged QRS duration ≥ 120 msec, average of triplicate electrocardiograms (ECGs)
- Part A_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.
- Part B_E1. Recent (< 90 days) acute coronary syndrome or angina pectoris
- Part B_E2. Coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft) within prior 90 days
- Part B_E3. Recent (< 90 days) hospitalization for heart failure, use of intravenous diuretic or chronic intravenous inotropic therapy or other cardiovascular event (eg, cerebrovascular accident)
- Part B_E4. Active infection, indicated clinically as determined by the Investigator. In the case of SARS-CoV-2 (COVID-19) infection within 4 weeks prior to Part B Baseline Visit or Rescreening (if required), 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. Due to character limitation, for other exclusion criteria, please refer to the protocol
- Part A_E5. Recent (< 90 days) acute coronary syndrome or angina pectoris
- Part A_E6. Coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft) within prior 90 days
- Part A_E7. Recent (< 90 days) hospitalization for heart failure, use of intravenous diuretic or chronic intravenous inotropic therapy or other cardiovascular event (eg, cerebrovascular accident)
- Part A_E8. Known aortic stenosis of moderate or greater severity
- Part A_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
- Part A_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
- Part A_E17. A life expectancy of < 6 months
The study team makes the final eligibility decision.
Where it's taking place
- United Kingdom
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United Kingdom; United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.