A study of aficamten (CK-3773274) in adults with symptomatic non-obstructive hypertrophic cardiomyopathy (ACACIA)

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] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

13 Sep 2024 → 27 Feb 2026

Decision date (initial)

2024-03-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Cytokinetics Inc.

External identifiers

EU CT number

2023-505797-15-00

ClinicalTrials.gov

NCT06081894

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To evaluate the effect of aficamten compared with placebo on participant health status and maximal exercise capacity

Secondary objectives 5

1. To evaluate the effect of aficamten compared with placebo on NYHA Functional Classification
2. To evaluate the effect of aficamten compared with placebo on maximal and sub-maximal exercise capacity
3. To evaluate the effect of aficamten compared with placebo on a biomarker of cardiac wall stress
4. To evaluate the effect of aficamten compared with placebo on echocardiographic measures of structural remodeling
5. To evaluate the effect of aficamten compared with placebo on cardiovascular events

Conditions and MedDRA coding

SYMPTOMATIC NON-OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Between 18–85 years of age at screening
2. Body mass index < 40 kg/m2
3. Diagnosed with nHCM and has a screening echocardiogram with the following: • End-diastolic LV wall thickness: − ≥ 15 mm in one or more myocardial segments OR − ≥ 13 mm in one or more wall segments AND a known disease-causing gene mutation or positive family history of HCM AND − Resting LVOT-G < 30 mmHg AND Valsalva LVOT-G < 50 mmHg AND − LVEF ≥ 60% • Participants with a history of intracavitary obstruction are eligible
4. New York Heart Association (NYHA) class II or III
5. Respiratory exchange ratio of ≥ 1.00 at screening by CPET and predicted peak oxygen uptake (pVO2) of ≤ 90% for age and sex
6. KCCQ-CSS score ≤ 85
7. N-terminal prohormone brain natriuretic peptide (NT-proBNP) of: • ≥ 300 pg/mL or ≥ 900 pg/mL if in atrial fibrillation or atrial flutter OR • For Black participants, ≥ 225 pg/mL or ≥ 675 pg/mL if in atrial fibrillation or atrial flutter
8. Hemoglobin ≥ 10 g/dL

Exclusion criteria 14

1. Significant valvular heart disease (per Investigator judgment) • Moderate or severe valvular aortic stenosis or fixed subaortic obstruction • Moderate or severe mitral regurgitation
2. Received prior treatment with aficamten
3. Received treatment with mavacamten within 3 months prior to screening (must be discussed with the medical monitor prior to screening)
4. Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics nHCM (e.g., Noonan syndrome, Fabry disease, amyloidosis)
5. Known current unrevascularized coronary artery stenosis of ≥ 70% or documented history of Type 1 myocardial infarction.
6. History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy
7. Inability to exercise on a treadmill or bicycle (e.g., orthopedic limitations)
8. Documented room air oxygen saturation reading < 90% at screening or history of significant chronic obstructive pulmonary disease or severe/significant pulmonary hypertension
9. History of the following events with exercise within 3 months prior to screening • syncope, • symptomatic ventricular arrhythmia, or • sustained ventricular tachyarrhythmia
10. History of resistant hypertension (persistently elevated blood pressure despite maximal doses of 3 or more classes of medications for hypertension control)
11. Screening diastolic blood pressure ≥ 100 mmHg
12. Undergone septal reduction therapy < 6 months prior to screening
13. Is being considered for or is likely to be considered for heart transplant listing or left ventricular assist device placement during the study period
14. Paroxysmal or permanent atrial fibrillation is excluded only if: • rhythm restoring treatment (e.g., direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤ 3 months prior to randomization • rate control and anticoagulation have not been achieved for at least 3 months prior to screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Dual primary endpoints of: • Change in KCCQ-CSS from baseline to Week 36 • Change in pVO2 from baseline to Week 36

Secondary endpoints 5

1. Proportion of participants with ≥ 1 class improvement in NYHA Functional Class from baseline to Week 36
2. Change in the composite of two Z-scores of CPET parameters from baseline to Week 36: – pVO2 (maximal exercise capacity) – VE/VCO2 slope (sub-maximal exercise capacity)
3. Change in NT-proBNP from baseline to Week 36
4. Change in LAVI from baseline to Week 36 in participants without atrial fibrillation or flutter at baseline on ECG.
5. Time to first event of cardiovascular death, heart transplantation or left ventricular assist device, aborted sudden cardiac death, non-fatal stroke, heart failure hospitalization, or cardiac arrhythmia (atrial fibrillation or ventricular tachyarrhythmia) requiring treatment or hospitalization

Investigational products

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

Test 1

Placebo 1

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

Cytokinetics Inc. Medical Affairs

Public contact point

Organisation

Cytokinetics Inc.

Contact name

Cytokinetics Inc. Medical Affairs

Third parties 12

Locations

11 EU/EEA countries · 48 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 133 files

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

Application history

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