ReVeRA-301: Etripamil in Atrial Fibrillation Phase 3

NCT06716021 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: MSP-2017-5002
• Study Type: interventional
• Target: 750
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multi-national, multi-center, randomized, double-blind, placebo-controlled study to evaluate the effects of etripamil NS in patients with atrial fibrillation (AF). This study includes Screening Visit, Randomization Visit, a Treatment Period with scheduled Follow-up Visits (Monthly Follow-up and Post-treatment Follow-up Visits), a Final Study Visit, and an End of Study Telephone Follow up Visit. Each patient will be randomized 1:1 to receive placebo or 70 mg Etripamil NS regimens. Patients will self-administer study drug for a perceived episode of AF with RVR with an initial dose of placebo or 70 mg etripamil NS, followed by an optional second dose of the same study drug 10 minutes after the first dose if the patient continues to experience symptoms. Patients may treat up to a maximum of 4 episodes in the study. Informed consent will be obtained prior to any study procedures.

Conditions

Atrial Fibrillation

Keywords

Atrial Fibrillation; Rapid Ventricular Rate; Rapid Ventricular Response; Ventricular Rate Control

Outcome Measures

Primary Outcomes (1)

• Demonstrate the efficacy of etripamil NS over placebo in patients with AF.

  The maximum reduction in ventricular rate, measured from ECG CMS recordings, within 30 minutes from first drug administration

  30 minutes from first drug administration

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients will self-administer an initial dose of placebo for a perceived episode of AF with RVR, followed by an optional second dose 10 minutes later if symptoms persist.

Drug: Placebo

Etripamil

EXPERIMENTAL

Patients will self-administer an initial dose of etripamil for a perceived episode of AF with RVR, followed by an optional second dose 10 minutes later if symptoms persist.

Drug: Etripamil

Interventions

Placebo DRUG

The formulation of placebo will consist of water, sodium acetate, disodium EDTA, and sulfuric acid to reproduce the same pH as the etripamil formulation.

Placebo

Etripamil DRUG

The formulation of etripamil is for IN administration and will consist of etripamil, water, acetic acid, disodium ethylene-diamine-tetra-acetic acid (EDTA), and sulfuric acid. The dose of etripamil to be evaluated in this study is 70 mg with an optional second dose of 70 mg 10 minutes after the first dose if symptoms persist.

Also known as: MSP-2017

Etripamil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years and over.
• Provision of written informed consent.
• Documented history of symptomatic AF (paroxysmal, persistent, or permanent) with a ventricular rate of ≥110 bpm.
• Documentation: electrocardiogram (ECG) tracing (including 12-lead ECG or ECG strip) showing AF with ventricular rate ≥110 beats per minute (bpm). This ECG documentation (anonymized with study Patient ID only) will be submitted to the Sponsor after screening and prior to randomization to confirm diagnosis of AF with RVR and eligibility to be randomized in the study. Patients who have undergone a prior ablation procedure for AF or for an AF-trigger must have documented AF with RVR post-ablation for study eligibility.
• Documented history of repeated (at least 2 within the prior 12 months) and prolonged (at least 20 minutes) symptomatic episodes of AF with elevated (perceived or measured) heart rate (HR).
• Documentation: Patient description, other history, or medical records. Patients who have undergone a prior ablation procedure for AF or for an AF-trigger must fulfill this criterion post-ablation for study eligibility.
• Receiving appropriate antithrombotic/anticoagulation therapy as per applicable national and/or local guidelines for AF management.
• Women of childbearing potential must have a negative pregnancy test at Screening and agree to use at least 1 highly effective form of contraception from time of randomization until 7 days after the last administration of study drug and must be willing to discontinue from the study should they become or plan to become pregnant.

You may not qualify if:

• Patients with a primary diagnosis of atrial flutter (typical or atypical) or atrial tachycardia. Patients with AF who have been observed to also experience atrial flutter within the same episode (i.e., "AFib/Flutter" or an admixture of AF and flutter within the same episode) are eligible.
• History of any of the following within the last 6 months: Class 3 or 4 angina per Canadian Cardiovascular Society (CCS) criteria; ischemic chest pain during AF episodes; acute coronary syndrome, unless the patient has been successfully revascularized; coronary artery bypass grafting or open-chest valve surgery.
• History of heart failure (HF) New York Heart Association (NYHA) classification ≥Class III within the last 3 months.
• The etiology of any HF should have been previously evaluated and addressed.
• HF with a reduced ejection fraction and/or HF with a preserved ejection fraction are acceptable.
• History of hemodynamic instability during AF, i.e., symptoms or signs of severe hypotension, or syncope due to a pause upon conversion from AF to sinus rhythm (SR).
• History of unexplained syncope.
• History of, or ECG evidence at the screening visit, of: sick sinus syndrome, Mobitz II second- or third-degree atrioventricular (AV) block bradycardia (\<40 bpm) or pauses \>3 seconds during waking hours, without a pacemaker.
• History of, or ECG evidence at the Screening visit, of: torsades de pointes, ventricular fibrillation, or ventricular tachycardia, Brugada syndrome, an antegrade conducting accessory bypass tract (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndromes), or long QT syndrome.
• History of stroke, transient ischemic attack or peripheral embolism within the last 3 months.
• CHA2DS2-VASc score of \>5.
• Planned AF or AV node ablation within the next 3 months.
• Uncorrected, severe aortic or mitral stenosis.
• Hypertrophic cardiomyopathy with outflow tract obstruction.
• History of sensitivity to verapamil or to any components of the investigational product.

Sponsors & Collaborators

• Milestone Pharmaceuticals Inc.: lead

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

etripamil

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• James E. Ip, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leonid Kokovin-Sher

CONTACT

450-912-6783; lkokovin-sher@milestonepharma.com

Silvia Shardonofsky, MD

CONTACT

450-912-6777; sshardonofsky@milestonepharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2024
• First Posted: December 4, 2024
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share