Aficamten for Heart Rhythm in Healthy Subjects

Overseen By Study Director Cytokinetics, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Cytokinetics

Disqualifiers: Alcohol, Drug abuse, others

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how the drug aficamten affects the heart's electrical activity, specifically the QT/QTc interval, which measures heartbeats. In the first part, researchers will establish the correct dose of aficamten. In the second part, they will compare the effects of this dose with a placebo (a harmless substance resembling the drug) and moxifloxacin (an antibiotic known to affect heart rhythm). The study seeks healthy, non-smoking individuals without significant medical issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the study is for healthy participants, it's likely that you should not be on any regular medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that aficamten is generally safe and well-tolerated. Earlier studies reported no major heart-related side effects linked to aficamten. However, about 5.6% of patients experienced serious side effects. Over time, aficamten proved effective in easing heart-related symptoms. Overall, evidence suggests that aficamten is safe, with only a few reports of serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about aficamten because it offers a novel approach to managing conditions affecting the heart's electrical activity, specifically the QT/QTc interval. Unlike existing treatments that primarily focus on controlling symptoms or slowing disease progression, aficamten works by targeting cardiac myosin, potentially leading to more precise control over heart function. This targeted action may reduce the risk of side effects often associated with broader treatments. Additionally, with varied dosing options being explored, aficamten could provide flexibility in treatment plans, allowing for personalized care based on individual patient needs.

What evidence suggests that aficamten administration could be effective for evaluating the QT/QTc interval?

Research shows that aficamten effectively treats patients with obstructive hypertrophic cardiomyopathy, a condition where the heart muscle thickens. One study demonstrated that aficamten provided significant and lasting relief from symptoms and blockage for 48 weeks. Another study found that it greatly improved patients' ability to exercise and recover. Multiple studies reported that the treatment was well tolerated, with a good safety record. This trial will assess different doses of aficamten and its effects on heart rhythm in healthy participants. Existing evidence supports aficamten's effectiveness for its main use in heart conditions. ^{1 3 5 6 7}

Who Is on the Research Team?

Cytokinetics, MD

Principal Investigator

Cytokinetics

Are You a Good Fit for This Trial?

Inclusion Criteria

Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 at the screening visit.

Continuous non-smoker who has not used nicotine- and tobacco-containing products for at least 3 months prior to the first dosing based on participant self-reporting.

Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, and vital signs, as deemed by the PI or designee, including the following:

Exclusion Criteria

You have a history of using drugs or alcohol excessively in the past two years.

History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A: Dose Finding

Open-label, single ascending dose study to identify the dose for Part B

8 weeks

Part B: TQT Study

Randomized, double-blind, placebo- and positive-controlled, single-dose, 3-way crossover study to evaluate the effect of aficamten on QT/QTc interval

14.5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aficamten Administration

How Is the Trial Designed?

Group I: Part B (TQT Study): Aficamten Experimental Treatment 1 Intervention

Participants will receive a single oral dose of aficamten. The dose will be determined based on review of Part A PK parameters, echocardiogram parameters, safety, and tolerability for aficamten.

Group II: Part A (Dose Finding Cohort 3): Aficamten 100 mg Experimental Treatment 1 Intervention

Participants in this arm will receive a single oral dose up to 100 mg aficamten.

Group III: Part A (Dose Finding Cohort 2): Aficamten 75 mg Experimental Treatment 1 Intervention

Participants in this arm will receive a single oral dose up to 75 mg aficamten.

Group IV: Part A (Dose Finding Cohort 1): Aficamten 50 mg Experimental Treatment 1 Intervention

Participants in this arm will receive a single oral dose of 50 mg aficamten.

Group V: Part B (TQT Study): Moxifloxacin 400 mg Active Control 1 Intervention

Participants will receive a single oral dose of 400 mg moxifloxacin

Group VI: Part B (TQT Study): Aficamten-matching Placebo Placebo Group 1 Intervention

Participants in this arm will receive a single oral dose of aficamten-matching placebo.

Who Is Running the Clinical Trial?

Cytokinetics

Lead Sponsor

Trials

44

Recruited

17,500+

Published Research Related to This Trial

The recent fatal adverse event in the BIA-102474-101 clinical trial highlights significant limitations in the current safety review process for first-into-human trials, despite previous trials with similar compounds being conducted without incident.

To improve safety in future trials, it is crucial to implement sequential dosing strategies, thorough reviews of preclinical toxicity studies, and systematic risk assessments, especially for novel compounds that may pose higher risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of the BIA-102474-101 study for review of first-into-human clinical trials. Eddleston, M., Cohen, AF., Webb, DJ.[2021]

A review of 73 migraine drug trials published between 2010 and 2015 found that while a majority reported adverse events, only 41% included this information in their abstracts, highlighting a gap in transparency.

The study emphasizes the need for all randomized controlled trials on migraine treatments to consistently report adverse events in their abstracts to better assess the safety and tolerability of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the reporting of adverse events in controlled clinical trials conducted in 2010-2015 on migraine drug treatments. Tfelt-Hansen, P., Lindqvist, JK., Do, TP.[2019]

In a review of 24 Phase I studies involving 430 healthy male volunteers over 5 years, the overall incidence of adverse events was 13.5%, with a higher rate for active drug treatments (15.3%) compared to placebo (7.4%).

Severe adverse events occurred in 20 cases (0.36%), but there were no deaths or life-threatening incidents, indicating that while adverse events are common, they are generally not severe in Phase I trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase one studies: a study in 430 healthy volunteers. Sibille, M., Deigat, N., Olagnier, V., et al.[2019]

In a study involving 24 healthy premenopausal women, flibanserin taken at bedtime after moderate alcohol consumption was well-tolerated, showing no significant increase in hypotension or syncope compared to placebo.

The study found that common adverse effects of flibanserin, such as headaches and hypotension, occurred at similar rates regardless of alcohol consumption, indicating that the timing of flibanserin dosing may mitigate risks associated with alcohol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Evening Ethanol Consumption and Bedtime Administration of Flibanserin in Healthy Premenopausal Female Subjects. Millheiser, L., Clayton, AH., Parish, SJ., et al.[2020]

In a review of 231 randomized placebo-controlled clinical trials, it was found that a staggering 96.8% of adverse events (AEs) reported in patients taking active drugs were nonspecific, meaning they were not directly related to the medication.

The study revealed strong correlations between AE rates in placebo and active-drug groups, indicating that many reported AEs may not be caused by the drug itself, which raises concerns about the reliability of clinical trial data in assessing drug tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials. Mahr, A., Golmard, C., Pham, E., et al.[2022]

The study analyzed 345,662 spontaneous reports of adverse drug reactions (ADRs) submitted to the German Federal Institute for Drugs and Medical Devices, revealing a steady increase in reports since 1978, primarily due to stricter legal reporting requirements.

The most commonly reported ADRs were linked to drugs for nervous system disorders, with significant differences in reporting patterns between physicians and patients, suggesting a need for better patient education on potential ADRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent Adverse Drug Reactions, and Medication Groups under Suspicion. Dubrall, D., Schmid, M., Alešik, E., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40540987/

48-Week Results From FOREST-HCM Aficamten treatment over 48 weeks was well tolerated and associated with substantial and durable relief of obstruction and symptom burden.

2. ir.cytokinetics.com ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Presents-New-Data-Related-to-Aficamten-at-the-HFSA-Annual-Scientific-Meeting-2025/default.aspx

Cytokinetics Presents New Data Related to Aficamten at ... Additional Data from MAPLE-HCM Show Aficamten Significantly Improves Measures of Maximal and Submaximal Exercise Capacity and Recovery ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.038758

Safety and Efficacy of Mavacamten and Aficamten in ... Safety outcome measures included frequency of treatment‐emergent adverse events (TEAE), serious adverse events, LVEF <50%, heart failure ( ...

4. academic.oup.com academic.oup.com/eurheartj/article/46/40/4076/8133640

Efficacy of aficamten in patients with obstructive hypertrophic ... Aficamten was administered orally at 5 mg once daily with three subsequent opportunities to undergo dose increase in 5-mg increments (at Weeks 2, 4, and 6), to ...

5. jacc.org jacc.org/doi/10.1016/j.jacc.2024.09.003

Impact of Aficamten on Disease and Symptom ... - JACC For each clinical efficacy outcome, week 24 data were applied when available. For patients with missing data, the last available observation ...

6. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.035993

Dosing and Safety Profile of Aficamten in Symptomatic ... There were no major adverse cardiovascular events associated with aficamten treatment in SEQUOIA‐HCM. Serious AEs occurred in 8 patients (5.6%) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1071916425004312

A 96-Week Analysis From FOREST-HCM If aficamten is found to be effective, safe, and achieves regulatory approval, the intended use would be chronic, therefore; long-term safety ...