Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten (CK-3773274) in Adults With Hypertrophic Cardiomyopathy (HCM)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cytokinetics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

31 Jan 2022 → ongoing

Decision date (initial)

2024-07-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Cytokinetics, Inc.

External identifiers

EU CT number

2023-508963-58-00

EudraCT number

2020-003571-17

ClinicalTrials.gov

NCT04848506

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic

To determine the safety and tolerability of aficamten in patients with symptomatic HCM

Secondary objectives 1

1. Assess long-term effects of aficamten on left ventricular outflow tract gradient (LVOT-G) in patients with obstructive HCM (oHCM)

Conditions and MedDRA coding

Symptomatic hypertrophic cardiomyopathy (HCM)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. 1. Completion of a Cytokinetics study investigating aficamten. If unable to complete due to circumstances not related to compliance or safety, Medical Monitor may review and determine eligibility.
2. 2. Left ventricular ejection fraction (LVEF) ≥ 55%.

Exclusion criteria 5

1. 1. Has received treatment with mavacamten: (a) within 56 days prior to dosing and (b) has not received approval for participation from the Medical Monitor.
2. 2. Has participated in another investigational device or drug study or received an investigational device or drug < 1 month (or 5 half-lives for drugs, whichever is longer) prior to screening. Other investigational procedures while participating in this study are not permitted.
3. 3. Since completion of a previous study of aficamten 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 < 100 bpm and/or rhythm is stable > 30 days. - Undergone septal reduction therapy (surgical myectomy or transcatheter alcohol ablation).
4. 4. Had a confirmed LVEF < 40% with an associated dose interruption during participation in a prior study with aficamten.
5. 5. History of implantable cardioverter-defibrillator (ICD) placement within 30 days prior to screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 1. Patient incidence of reported adverse events (AEs)
2. 2. Patient incidence of reported serious adverse events (SAEs)
3. 3. Patient incidence of left ventricular ejection fraction (LVEF) <50%

Secondary endpoints 2

1. 1. Change from baseline values through end of participation in: − Peak LVOT-G at rest and with Valsalva provocation − 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. 2. Time to the following event through last follow-up - 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cytokinetics Inc.

Sponsor organisation

Cytokinetics Inc.

Address

350 Oyster Point Boulevard

City

South San Francisco

Postcode

94080-1912

Country

United States

Scientific contact point

Organisation

Cytokinetics Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Cytokinetics Inc.

Contact name

Medical Affairs

Third parties 7

Locations

12 EU/EEA countries · 58 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 107 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

18 submissions — initial application plus substantial / non-substantial modifications