Trial Details

A Phase 2, Two-Stage, Serial Cohort Dose Escalation and Expansion Study of a Single Intravenous Infusion of HBI 3000 for the Conversion of Atrial Fibrillation (AF) of Recent Onset

NCT04680026

ACTIVE_NOT_RECRUITING

DESCRIPTION

This Phase 2 study is a two-stage, serial cohort dose escalation and expansion study of a single 30-minute (IV) infusion of HBI-3000 for the conversion of patients with recent-onset atrial fibrillation (AF). Stage A is open label and all patients will receive HBI-3000. In each of three dose cohorts, up to 10 patients will receive HBI-3000 by IV infusion (30 minutes). Three different dose levels are planned to be administered serially, lowest to highest, with assessment of safety, tolerability, and efficacy prior to proceeding to the next dose level group. Following Stage A, the iDMC will recommend up to two doses of HBI-3000 to be further explored in Stage B. Stage B is a serial, randomized, double-blind and placebo-controlled cohort of two different doses of HBI-3000, with a dose decision after the first cohort. Stage B will be powered to show a difference between HBI-3000 and placebo in conversion rate at each of the two dose levels.

CONDITIONS

ELIGIBILITY CRITERIA

• Inclusion Criteria
• :
• 18 to 80 years of age
• Sustained AF of \> 2 hours and \< 72 hours duration
• Eligible for cardioversion (electrical and pharmacologic)
• On adequate anticoagulant therapy or eligible for anticoagulation during treatment and for at least 30 days duration after treatment if indicated by ACC/AHA/HRS or country specific national or international guidelines for thromboembolic risk reduction related to AF
• Exclusion Criteria
• :
• Atrial fibrillation \< 2 hours or \> 72 hours duration or with duration not reliably established at the time of dosing
• Hemodynamic instability that may require emergency electrical cardioversion
• Atrial flutter
• Moderate to severe HF
• Clinical or ECG signs of acute cardiac ischemia or digitalis toxicity
• Known or suspected hyperthyroidism
• Cardiac surgery, stroke, TIA, acute MI/ PCI, unstable angina, or persistent angina at rest within the previous 3 months
• Presence of LA thrombus by TEE or TTE
• Presence of concurrent myocarditis or endocarditis
• ECG abnormalities: Current QTcF \> 480 msec; QRS interval \> 120 msec and/or a complete bundle branch block (BBB)l Delta wave or other pre-excitation pattern consistent with WPW syndrome; Acute coronary ischemia patterns
• Use of medication that prolongs the QTc interval or history of: Long QT syndrome, congenital or acquired; Torsades de Pointes (TdP); Brugada Syndrome; Ventricular arrhythmia (not including infrequent isolated PVC)
• Concurrent treatment with Class I or III antiarrhythmic drugs, metformin or strong CYP2D6 inhibitors (unless the medication is discontinued \> 5 half-lives before enrollment)
• Treatment with oral amiodarone in the previous 3 months or IV amiodarone administered within 24 hours prior to planned Study Drug administration
• Use of vernakalant, or any experimental drug within 30 days or five half-lives (whichever is longer) of Study Drug administration, or use of an invasive investigational medical device within 2 months prior to Study Drug administration, or current enrollment in another study with investigational agent or procedure
• Clinically significant laboratory abnormalities