Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten in Adults With HCM

Официальное название

A Follow-Up, Open-Label, Research Evaluation of Sustained Treatment With Aficamten (CK-3773274) in Hypertrophic Cardiomyopathy (HCM)

Обзор

The purpose of this study is to collect long-term safety and tolerability data for aficamten.

Вмешательства

• Препарат Aficamten (5 - 20 mg)
  Aficamten tablets administered orally. During titration phase, clinic visits will occur approximately every 2-6 weeks. In the maintenance phase clinic visits will occur every 24 weeks, with safety check-in occurring every 12 weeks between visits by phone or, if desirable, in the clinic.

Первичные конечные точки

• Incidence of adverse events observed during dosing of aficamten in patients with HCM [Срок оценки: Baseline to End of study, up to 5 years]

Вторичные конечные точки (11)

• Incidence of serious adverse events observed during dosing of aficamten in patients with HCM [Срок оценки: Baseline to End of study, up to 5 years]
• Incidence of left ventricular ejection fraction (LVEF) < 50% observed during dosing of aficamten in patients with HCM [Срок оценки: Baseline to End of study, up to 5 years]
• Long-term effects of aficamten on left ventricular outflow tract gradient (LVOT G) in patients with oHCM [Срок оценки: Baseline through the end of participation at 12-24 week intervals]
• Long-term effects of aficamten on resting LVOT-G [Срок оценки: Baseline through the end of participation at 12-24 week intervals]
• Long-term effects of aficamten on post Valsalva LVOT-G [Срок оценки: Baseline through the end of participation at 12-24 week intervals]
• Long-term effects of aficamten on post Valsalva LVOT-G [Срок оценки: Baseline through the end of participation at 12-24 week intervals]
• Long-term effects of aficamten on left ventricular ejection fraction (LVEF) and post-Valsalva LVOT-G [Срок оценки: Baseline through the end of participation at 12-24 week intervals]
• Long-term effects of aficamten on time to first resting LVOT-G < 30 mmHg through last follow-up [Срок оценки: Time to the following event through last follow-up, up to 5 years]
• Long-term effects of aficamten on time to first post-Valsalva LVOT-G < 50 mmHg through last follow-up [Срок оценки: Time to the following event through last follow-up, up to 5 years]
• Long-term effects of aficamten on time to first post-Valsalva LVOT-G < 30 mmHg through last follow-up [Срок оценки: Time to the following event through last follow-up, up to 5 years]
• Long-term effects of aficamten on time to first LVEF ≥ 50%, resting LVOT-G < 30 mmHg, and post-Valsalva LVOT-G < 50 mmHg through last follow-up [Срок оценки: Time to the following event through last follow-up, up to 5 years]

Критерии участия

Критерии включения

• Completion of a Cytokinetics trial investigating aficamten
• LVEF ≥ 55% at the Screening Visit

Критерии исключения

• Has received treatment with mavacamten: (a) within 56 days prior to dosing and (b) has not received approval for participation from the Medical Monitor.
• 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.
• Since completion of a previous trial 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 (HR) < 100 bpm and/or rhythm is stable > 30 days
• Undergone septal reduction therapy (surgical myectomy or transcatheter alcohol ablation)
• Had a confirmed LVEF < 40% with an associated dose interruption during participation in a prior study with aficamten
• History of implantable ICD placement within 30 days prior to screening.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 52 центра

• University of Alabama at Birmingham — Birmingham
• Alaska Heart and Vascular Institute — Anchorage
• Mayo Clinic Building - Phoenix — Phoenix
• UC San Diego Health - Sulpizio Cardiovascular Center — La Jolla
• Cedar-Sinai Medical Center — Los Angeles
• Cedars-Sinai Medical Center (Smidt Heart Institute) — Los Angeles
• UCSF Medical Center — San Francisco
• Yale New Haven Hospital — New Haven
• … и ещё 44 центра

Испания · 12 центров

Список центров уточняется — проверьте первичный протокол.

Франция · 9 центров

• Hopital de la Timone Service de cardiologie — Marseille
• Clinique Du Millenaire — Montpellier
• CHU Montpellier - Hopital Arnaud de Villeneuve — Montpellier
• CHU de Nantes Institut Du Thorax et du systeme nerveux Clinique Cardiologique et des Malad — Nantes
• Hopital Lariboisiere — Paris
• Hopital Europeen Georges Pompidou — Paris
• Hopital cardiologique de Haut-Leveque — Pessac
• Centre hospitalier universitaire (CHU) de Rennes-Hopital Pontchaillou — Rennes
• … и ещё 1 центр

Великобритания · 8 центров

Список центров уточняется — проверьте первичный протокол.

Италия · 7 центров

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Германия · 6 центров

• Charite-Universitaetsmedizin Berlin — Berlin
• Universitaetsklinikum Essen — Essen
• Universitaetsmedizin Goettingen Klinik fur Kardiologie und Pneumologie — Goettigen
• Universitaesklinkum Heidelberg — Heidelberg
• Universitaetsklinikum Jena — Jena
• … и ещё 1 центр

Дания · 5 центров

• Department of Cardiology Aalborg University Hospital — Aalborg
• Department of Cardiology Aarhus University Hospital — Aarhus
• The Heart Center, Department of Cardiology — Copenhagen
• Copenhagen University Hospital — Copenhagen
• Odense University Hospital — Odense

Израиль · 5 центров

Список центров уточняется — проверьте первичный протокол.

Греция · 4 центра

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Португалия · 4 центра

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Австралия · 3 центра

• Flinders Medical Centre, Cardiology Research — Bedford Park
• The Prince Charles Hospital — Chermside
• Fiona Stanley Hospital, AHF Unit — Murdoch

Канада · 3 центра

• Institut universitaire de cardiologie et de pneumologie de Quebec-Universite Laval — Québec
• Royal Alexandra Hospital — Edmonton
• QEII Health Science Centre (Halifax Infirmary site) — Halifax

Нидерланды · 3 центра

Список центров уточняется — проверьте первичный протокол.

Венгрия · 2 центра

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Польша · 2 центра

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Аргентина · 1 центр

• Instituto Cardiovascular de Buenos Aires(ICBA) — Buenos Aires

Бразилия · 1 центр

• Instituto Dante Pazzanese de Cardiologia — São Paulo

Чехия · 1 центр

• Il. Interni klinika kardiologie a angiologie — Prague

Iceland · 1 центр

Список центров уточняется — проверьте первичный протокол.

Публикации

• Saberi S, Abraham TP, Choudhury L, Barriales-Villa R, Elliott PM, Nassif ME, Oreziak A, Owens AT, Tower-Rader A, Rader F, Garcia-Pavia P, Olivotto I, Coats CJ, Fifer MA, Sherrid MV, Solomon SD, Watkins H, Heitner SB, Jacoby DL, Kupfer S, Malik FI, Melloni C, Meng L, Wei J, Maron MS, Masri A; FOREST-HCM Steering Committee and Investigators. Aficamten Treatment for Symptomatic Obstructive Hypertroph PMID 40540987
• Masri A, Maron MS, Abraham TP, Nassif ME, Barriales-Villa R, Bilen O, Coats CJ, Elliott P, Garcia-Pavia P, Massera D, Olivotto I, Oreziak A, Owens AT, Saberi S, Solomon SD, Tower-Rader A, Heitner SB, Jacoby DL, Melloni C, Wei J, Sherrid MV; REDWOOD-HCM, SEQUOIA-HCM, and FOREST-HCM Investigators. Concomitant Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy. JACC Hea PMID 40285763
• Masri A, Choudhury L, Barriales-Villa R, Elliott P, Maron MS, Nassif ME, Oreziak A, Owens AT, Saberi S, Tower-Rader A, Rader F, Garcia-Pavia P, Olivotto I, Nagueh SF, Wang A, Heitner SB, Jacoby DL, Kupfer S, Malik FI, Melloni C, Meng L, Wei J, Sherrid MV, Abraham TP; FOREST-HCM Investigators. Standard-of-Care Medication Withdrawal in Patients With Obstructive Hypertrophic Cardiomyopathy Receiving PMID 39477631

Идентификаторы

NCT: NCT04848506 · CY 6022 · 2020-003571-17 · 2023-508963-58-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗