This study is being performed to collect long-term safety and tolerability data of CK-3773274 on patients with obstructive hypertrophic cardiomyopathy (oHCM).

• Register: EUCTR
• Last refreshed on: 17 August 2021
• Main ID: EUCTR2020-003571-17-ES
• Date of registration: 14/07/2021
• Prospective Registration: Yes
• Primary sponsor: Cytokinetics, Inc.
• Public title: This study is being performed to collect long-term safety and tolerability data of CK-3773274 on patients with obstructive hypertrophic cardiomyopathy (oHCM).
• Scientific title: An Open-Label Study of CK-3773274 for Patients with Symptomatic Hypertrophic Cardiomyopathy (HCM) and Left Ventricular Outflow Tract Obstruction.
• Date of first enrolment: 11/08/2021
• Target sample size: 54
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-003571-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy, Spain, United States

Contacts

• Name: Medical Affairs
• Affiliation: Cytokinetics Inc

• Name: Medical Affairs
• Affiliation: Cytokinetics Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Patients are eligible to be included in the study only if all the following criteria apply:
1. Able to comprehend and willing to sign an ICF and willing to comply with all study procedures and restrictions for the duration specified in the Schedule of Activities.

2. Completion of a Cytokinetics trial investigating CK-3773274. If unable to complete due to circumstances not related to compliance or safety, Medical Monitor may review and determine eligibility.

3. Left ventricular ejection fraction = 55%.

4. Male patients are eligible to participate if they agree to the following during the study and for at least 10 weeks after the last dose of IP:
a. Refrain from donating sperm
Plus either:
b. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
OR
Must agree to use a male condom and, when his female partner is a woman of childbearing potential, have his female partner use a highly effective method of contraception (as described in Appendix 3 [Section 10.3] of the protocol)

5. A female patient is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
a. Is not a woman of childbearing potential (WOCBP; as described in Appendix 3 [Section 10.3] of the protocol)
OR
Is a WOCBP and using a highly effective method of contraceptive (as described in Appendix 3 [Section 10.3]) during the study and for at least 4 weeks after the last dose of IP.
b. A WOCBP must have a negative pregnancy test (urine or serum as required by local regulations) within 3 days before the first dose of study intervention.
Note: The Principal Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Contraceptive use by men or WOCBPs should be consistent with the guidance in Appendix 3 (Section 10.3) and local regulations regarding the methods of contraception for those participating in clinical studies.

6. Willing and able to complete all screening procedures.
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 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion criteria:
• Has taken any investigational study drug other than CK-3773274 within 30 days prior to screening.

• Since completion of a previous trial of CK-3773274 has:
- Developed new-onset paroxysmal or permanent atrial fibrillation requiring rhythm restoring treatment (eg, direct-current cardioversion, ablation procedure, or antiarrhythmic therapy) <30 days prior to screening. Patient may re-screen for CY 6022 after 30 days if heart rate (HR) <100 bpm and/or rhythm is stable >30 days.

- Undergone septal reduction therapy (surgical myectomy or transcatheter alcohol ablation).

• Has current obstructive coronary artery disease (>70% stenosis documented in one or more arteries).

• Has moderate or severe aortic valve stenosis.

• Had a confirmed LVEF <40% with an associated dose interruption during CY 6021. If data from the participant's cohort has been unblinded, the patient may be considered for entry into CY 6022 (see Section 6.6.1 of the protocol).

• Has been treated with drugs that have negative inotropic activity within 30 days prior to screening.

• History of syncope or sustained ventricular tachyarrhythmia with exercise within 30 days prior to screening.

• History of appropriate ICD shock within 30 days prior to screening.

• Has received treatment with mavacamten within 3 months prior to screening.


Exclusion Criteria for CMR sub-study:
• Inability to tolerate CMR.

• Has an implantable cardioverter-defibrillator (ICD).

• Has a cardiac pacemaker.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

obstructive hypertrophic cardiomyopathy (oHCM)
MedDRA version: 20.0 Level: PT Classification code 10020871 Term: Hypertrophic cardiomyopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Code: CK-3773274
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: CK-3773274
Current Sponsor code: CK-3773274
Other descriptive name: (R)-N-(5-(5-ETHYL-1,2,4-OXADIAZOL-3-YL)-2,3-DIHYDRO-1H-INDEN-1-YL)-1-METHYL-1H-PYRAZOLE-4-CARBOXAMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Code: CK-3773274
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: CK-3773274
Current Sponsor code: CK-3773274
Other descriptive name: (R)-N-(5-(5-ETHYL-1,2,4-OXADIAZOL-3-YL)-2,3-DIHYDRO-1H-INDEN-1-YL)-1-METHYL-1H-PYRAZOLE-4-CARBOXAMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: To determine the safety and tolerability of CK-3773274 in patients with symptomatic oHCM

Secondary Objective: To assess long-term effects of CK-3773274 on left ventricular outflow tract gradient (LVOT-G)

To assess steady-state PK during long-term administration of CK-3773274

Timepoint(s) of evaluation of this end point: End of participation

Primary end point(s): • Patient incidence of reported adverse events (AEs)

• Patient incidence of reported serious adverse events (SAEs)

• Patient incidence of left ventricular ejection fraction (LVEF) <50%

Secondary Outcome(s)

Secondary end point(s): 1. Change from baseline values at 12-week intervals through end of participation in:
- Peak LVOT-G at rest and with Valsalva provocation

- Proportion of patients with resting LVOT-G <50 mmHg

- Proportion of patients with resting LVOT-G <30 mmHg

- Proportion of patients with post-Valsalva LVOT-G <50 mmHg

- Proportion of patients with post-Valsalva LVOT-G <30 mmHg

- Proportion of patients with LVEF =50%, resting LVOT-G <30 mmHg, and post-Valsalva LVOT-G <50 mmHg

2. Time to the following event through last follow-up
- First resting LVOT-G <50 mmHg

- First resting LVOT-G <30 mmHg
- First post-Valsalva LVOT-G <50 mmHg

- First post-Valsalva LVOT-G <30 mmHg

- First LVEF =50%, resting LVOT-G <30 mmHg, and post-Valsalva LVOT-G <50 mmHg

3. C^trough at 12-week intervals through end of participation

Timepoint(s) of evaluation of this end point: End of participation

Secondary ID(s)

CY6022

Source(s) of Monetary Support

Cytokinetics, Inc.

Ethics review

Status: Approved
Approval date: 10/08/2021
Contact: