What side effects are associated with this type of intervention?

Treatments for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) that target and repair leaky Ryanodine Receptor calcium release channels, such as S48168 (ARM210), can have side effects including arrhythmias, hypotension, and potential exacerbation of heart failure symptoms. As these are often novel therapies, there may also be risks of off-target effects, immune reactions, or other unforeseen complications. Careful monitoring is essential to manage these side effects effectively.

What prior FDA approvals exist?

There is no specific mention of prior FDA approvals for drugs treating Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) that repair leaky Ryanodine Receptor calcium release channels in the provided context. Generally, CPVT is managed with beta-blockers, calcium channel blockers, and in some cases, implantable cardioverter-defibrillators (ICDs). The novel small molecule drug S48168 (ARM210) represents a potential new approach by directly targeting and repairing the defective calcium channels.

What other types of research exist?

A-1048400 is a novel, orally active, state-dependent neuronal calcium channel blocker that produces dose-dependent antinociception without altering hemodynamic function. It has shown efficacy in blocking calcium channels and reversing tactile allodynia in preclinical models. Another potential alternative is SB 201823-A, a non-peptide Ca2+ channel antagonist that has demonstrated neuroprotective effects in models of cerebral ischemia. Both compounds represent promising alternatives for CPVT treatment in 2024.

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Small Molecule Drug

ARM210 for Ventricular Tachycardia

Phase 2

Waitlist Available

Led By Michael J Ackerman, MD PhD

Research Sponsored by Armgo Pharma, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants have a confirmed genetic diagnosis of CPVT1 and supporting clinical phenotype, including residual ventricular ectopy on a stable standard-of-care, CPVT1-directed treatment regimen

Is a woman of non-childbearing potential

Must not have

Is mentally or legally incapacitated at the time of screening visit

Is unable to take orally administered tablets

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 days

Summary

This trial tests a new drug, S48168 (ARM210), for people with a heart condition called CPVT1. The drug aims to fix faulty heart cell channels caused by genetic mutations, helping patients live normal lives without dangerous heart rhythms.

Who is the study for?

Adults aged 18-65 with a confirmed genetic diagnosis of CPVT1 and related symptoms, who can follow the study plan and are not pregnant or breastfeeding. They must have a BMI ≤ 36 kg/m2, no recent drug abuse, controlled diabetes if present, no significant heart issues in the past five years, and agree to avoid certain medications and blood donations before and during the trial.

What is being tested?

The trial is testing S48168 (ARM210), which aims to fix leaky calcium channels caused by CPVT1 mutations that lead to dangerous heart rhythms. Participants will either receive this new drug or a placebo without knowing which one they're getting to compare effectiveness.

What are the potential side effects?

While specific side effects for S48168 (ARM210) aren't listed here, common ones for new drugs targeting heart conditions may include dizziness, headache, nausea, potential allergic reactions or changes in blood pressure or heart rhythm.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have CPVT1 with symptoms, even on my current treatment.

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I cannot become pregnant.

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I am between 18 and 65 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not mentally or legally able to make decisions at the time of screening.

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I cannot take pills by mouth.

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My diabetes is not under control, with an HbA1c over 7% or I have diabetic neuropathy.

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I can avoid drugs affecting CYP2C8 enzymes for 28 days before and during the study.

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I have had a heart attack in the last 5 years or have heart failure.

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I do not have significant heart issues apart from high blood pressure.

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My kidney function is reduced, with a creatinine clearance below 40 mL/min.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 28 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~28 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 28 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

The effect of S48168 (ARM210) treatment on the amount and complexity of exercise-• Change in ectopy score from baseline to Day 28 versus placebo (pre-dose Period 1 baseline to Day 28 Period 1 versus Day 28 Period 2

Secondary study objectives

Incidence of Treatment-Emergent Adverse Events

Other study objectives

Evaluation of a novel expanded ectopy scale in exercise stress tests which qualifies both the ectopy and the heart rate at which it occurs.

Evaluation of heart rhythm throughout treatment periods

The pharmacokinetics (PK) of a 28-day administration of S48168 (ARM210) in patients

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Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: S48168 (ARM210) once daily for 28 daysExperimental Treatment1 Intervention

Oral dose of S48168 (ARM210) once daily on top of standard of care regimen for 28 days.

Group II: Matching Placebo once daily for 28 daysPlacebo Group1 Intervention

Oral dose of placebo once daily on top of standard of care regimen for 28 days.

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a condition characterized by abnormal heart rhythms triggered by physical activity or stress, often due to mutations in the Ryanodine Receptor (RyR2) calcium release channels. These mutations cause the channels to become 'leaky,' leading to abnormal calcium handling in heart cells, which can precipitate dangerous arrhythmias. Treatments for CPVT aim to stabilize these channels and prevent arrhythmias. Beta-blockers are commonly used to reduce the heart's response to adrenaline, thereby lowering the risk of arrhythmias. Flecainide, an antiarrhythmic drug, can also be used to block abnormal electrical activity. The novel drug S48168 (ARM210) specifically targets and repairs the leaky RyR2 channels, addressing the root cause of CPVT. This mechanism is crucial as it directly corrects the defective calcium handling, potentially offering a more effective and targeted treatment option for CPVT patients.