Milestone Enrolls First Canadian Patient in ReVeRA-301 Phase 3 Trial of Etripamil Nasal Spray for AFib-RVR
核心洞察
The Montreal Heart Institute (搜索), the first activated Canadian site for the ReVeRA-301 Phase 3 pivotal trial, has enrolled its first patient, advancing the multinational study toward a target of 150 treated AFib-RVR events.
ReVeRA-301 is a randomized, double-blind, placebo-controlled study of a self-administered 70 mg repeat-dose etripamil regimen, the same regimen FDA-approved for PSVT as CARDAMYST.
The primary endpoint is reduction in ventricular rate within 30 minutes, with symptom improvement measured by patient-reported outcomes as a key secondary endpoint.
Milestone Pharmaceuticals announced that the Montreal Heart Institute (搜索), recently activated as the first Canadian clinical trial site for the ReVeRA-301 Phase 3 pivotal trial, has enrolled its first patient. The trial is evaluating etripamil nasal spray for the treatment of atrial fibrillation with rapid ventricular rate (搜索) (AFib-RVR). The Canadian enrollment follows the recent first enrolled patient in the United States and advances the multinational study toward its target of 150 patients with treated AFib-RVR events.
"Activating clinical trial sites and enrolling study participants in Canada are important steps toward advancing ReVeRA-301 and reflect the momentum behind our global enrollment efforts following the recent first enrolled patient in the United States," said David Bharucha, M.D., PhD, FACC, Chief Medical Officer of Milestone Pharmaceuticals. "We are honored to continue our work with the strong Canadian community of cardiovascular investigators and centers with deep experience in atrial fibrillation research."
Trial Design and Dosing
ReVeRA-301 is a Phase 3 multinational, multi-center, randomized, double-blind, placebo-controlled study designed to evaluate etripamil nasal spray in approximately 150 patient events with AFib-RVR. Prompted by symptoms, patients self-administer the drug in a medically unsupervised setting, such as at home. The regimen is the same 70 mg dose and repeat-dose schedule that supports the current FDA indication for the treatment of paroxysmal supraventricular tachycardia (搜索) (PSVT).
The primary endpoint is reduction in ventricular rate (VR) within 30 minutes. The study will also evaluate a key secondary endpoint of symptom improvement via patient-reported outcomes. Clinical trial sites and enrollment information are listed at clinicaltrials.gov.
Based on safety data demonstrated to date, Milestone is currently pursuing a single-study supplemental new drug application (sNDA) registration pathway for the treatment of AFib-RVR.
"The ability to intervene promptly with a self-administered therapy outside of the emergency department could represent a meaningful change for patients living with this condition," said Adrian Petzl, M.D., Cardiologist-Electrophysiologist at the Montreal Heart Institute (搜索) and an investigator on ReVeRA-301. "Following the promising Phase 2 data, we are pleased to advance etripamil into this pivotal Phase 3 trial in AFib-RVR."
Phase 2 Foundation
ReVeRA-301 advances research from ReVeRA-201, a multi-center Phase 2 randomized controlled study of the efficacy and safety of etripamil nasal spray for the acute reduction of symptomatic AFib-RVR in an emergency room setting. That trial showed that a single 70 mg dose of etripamil nasal spray reduced VR and improved both relief of symptoms and treatment satisfaction.
Disease Burden and Current Management
Atrial fibrillation is the most common sustained arrhythmia, affecting over 6 million people in the United States. The Canadian Cardiovascular Society estimates that AFib affects approximately 1 to 2 percent of the population in Canada, up to approximately 800,000 people, and represents a substantial and growing public health burden. AFib presents with an irregular heart rate and is classified as paroxysmal, persistent, or permanent; a rapid heart rate during AFib is referred to as AFib-RVR.
Market research indicates that 30 to 40 percent of patients with AFib experience at least one episode of RVR per year requiring urgent medical attention. These episodes commonly cause palpitations, shortness of breath, and weakness. While AFib is rarely life-threatening, it is a serious condition that often requires treatment and increases the risk of serious complications if not properly managed. Current options for acute AFib-RVR management are limited and often involve an emergency department visit for IV beta blockers, IV calcium channel blockers, or electrical cardioversion.
Approved PSVT Indication and Pipeline
CARDAMYST (etripamil) nasal spray is approved by the U.S. Food and Drug Administration for the conversion of acute symptomatic episodes of PSVT to sinus rhythm in adults. It is a novel calcium channel blocker nasal spray designed as a self-administered rapid response therapy, bypassing the need for immediate medical oversight. The product is intended to give health care providers a new treatment option to enable on-demand care and patient self-management.
CARDAMYST is supported by a robust clinical trial program that includes a completed Phase 3 clinical-stage program for the treatment of PSVT. Etripamil is currently in Phase 2 development for the treatment of PSVT in pediatric patients and in Phase 3 development for control of acute AFib-RVR in adults.
The most common side effects of CARDAMYST include nasal discomfort, nasal congestion, runny nose, throat irritation, and nosebleed. The label also carries a warning for fainting due to the drug's effects on blood pressure, heart rate, and electrical activity of the heart, and lists contraindications including moderate to severe heart failure, Wolff-Parkinson-White syndrome, Lown-Ganong-Levine syndrome, pre-excitation on ECG, sick sinus syndrome without a permanent pacemaker, and second degree or higher atrioventricular block.