A Study of IV HBI-3000 for the Conversion Recent Onset Atrial Fibrillation (AF)

Atrial Fibrillation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04680026
• Other study ID #: HBI-3000-402
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 1, 2021
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: HUYABIO International, LLC.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

This is a two-stage study in patients with AF of recent onset:

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). For each dosing cohort, sentinel dosing is planned. Each patient may enroll only once in the study, will be enrolled into only one dose cohort and receive only a single dose treatment. In Stage A, 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. The actual dose levels may be modified, and additional dose levels may be considered based on the observed results at each cohort.

Stage B is the randomized, double-blind and placebo-controlled part of the study. Study drug for Stage B patients is either HBI-3000 or placebo. Two cohorts will be enrolled sequentially, lowest dose level first, with safety, efficacy, and available PK results evaluated by the Sponsor and iDMC prior to enrolling patients in the next/higher dose cohort. The dose level for the second cohort may be adjusted following interim review of results in the first cohort. Patients will be randomized to receive a single IV infusion of HBI 3000 or placebo over 30 minutes. In each of the dose cohorts, sequentially enrolled patients will be randomized at 2:1 ratio so that 40 patients will receive HBI 3000 infusion and 20 patients will receive placebo infusion. Each patient may enroll only once in the study, will be enrolled into only one dose cohort and receive only a single dose treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• HBI-3000
Small molecule, multi-ion channel blocker
• Placebo
Normal saline

Locations

Country	Name	City	State
Bosnia and Herzegovina	University Clinical Center of the Republic of Srpska	Banja Luka
Bosnia and Herzegovina	Cardiology Department, PHI Hospital Sveti Vracevi	Bijeljina
Bosnia and Herzegovina	University Clinical Center Tuzla	Tuzla
Canada	Centre hospitalier de L'Universite de Montral (CHUM)	Montréal	Quebec
Canada	Montreal Heart Institute	Montréal	Quebec
Canada	Centre integre de sante et de services sociaux de Lanaudiere - Hopital Pierre-Le Gardeur	Terrebonne	Quebec
New Zealand	Waikato Hospital	Hamilton
New Zealand	Wellington Regional Hospital	Wellington
Serbia	Clinical Hospital Center Zvezdara	Belgrade
Serbia	Dedinje Institute for Cardiovascular Diseases	Belgrade
Serbia	University Clinical Center of Serbia	Belgrade
Serbia	University Hospital Medical Center Bezanijska kosa	Belgrade
Serbia	Niš University Clinical Center	Niš	Bulevar Doktora
Serbia	Health Center Uzice	Užice
United States	AMG Heart and Vascular Center	Bartlesville	Oklahoma
United States	UofL Health - UofL Physicians, Cardiology Associates	Louisville	Kentucky
United States	NCH Research Institute	Naples	Florida
United States	HonorHealth Research Institute and Innovation	Scottsdale	Arizona
United States	Prairie Education & Research	Springfield	Illinois
United States	Ascension St. John Clinical Research Institute	Tulsa	Oklahoma
United States	North Mississippi Medical Center	Tupelo	Mississippi
United States	CHRISTUS Trinity Mother Frances Hospital - Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
HUYABIO International, LLC.

Countries where clinical trial is conducted

United States,  Bosnia and Herzegovina,  Canada,  New Zealand,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the safety of intravenously (IV) administered HBI-3000 in patients with Atrial Fibrillation (AF) of recent onset, as measured by the incidence of adverse events (AEs)	Evaluate the safety of intravenously (IV) administered HBI-3000 in patients with Atrial Fibrillation (AF) of recent onset, as measured by the incidence of adverse events (AEs)	30 days
Primary	Evaluate the safety of intravenously (IV) administered HBI-3000 in patients with Atrial Fibrillation (AF) of recent onset, as measured by changes in heart rate (HR)	Evaluate the safety of intravenously (IV) administered HBI-3000 in patients with Atrial Fibrillation (AF) of recent onset, as measured by change in heart rate (HR) from baseline (prior to Study Drug infusion) to study timepoints during and after Study Drug infusion, specifically: HR < 40 bpm for 2 minutes or longer within 90 minutes of initiation of the infusion; HR increase > 25 percent before conversion to SR (based on one minute averages compared between the event and the first minute of stable telemetry); HR > 120 bpm for one minute or longer after conversion to SR and within 90 minutes of initiation of the infusion	90 minutes
Primary	Evaluate the safety of intravenously (IV) administered HBI-3000 in patients with Atrial Fibrillation (AF) of recent onset, as measured by change in blood pressure (BP)	Evaluate the safety of intravenously (IV) administered HBI-3000 in patients with Atrial Fibrillation (AF) of recent onset, as measured by changes in blood pressure (BP) from baseline (prior to Study Drug infusion) to study timepoints during and after Study Drug infusion, specifically: Systolic BP < 90 mmHg for > 1 minute during SR and within 90 minutes of initiation of the infusion	90 minutes
Primary	Evaluate the safety of intravenously (IV) administered HBI-3000 in patients with Atrial Fibrillation (AF) of recent onset, as measured by ECG interval changes above a specific level	Evaluate the safety of intravenously (IV) administered HBI-3000 in patients with Atrial Fibrillation (AF) of recent onset, as measured by ECG interval changes from baseline (prior to Study Drug infusion) to 24 hour post-infusion, specifically: QTcF: > 500 msec and > 60 msec above the 24-hour post-conversion level during SR; PR: > 50 percent above the 24-hour post-conversion level during SR; QRS: = 33 percent above the 24-hour post-conversion level during SR	24 hours
Primary	The efficacy of intravenously (IV) administered HBI-3000 as measured by the proportion of patients with AF of recent onset who convert to SR	Evaluate the efficacy of intravenously (IV) administered HBI-3000 in patients with Atrial Fibrillation (AF) of recent onset as measured by the proportion of patients with AF of recent onset who convert to SR (for a duration of at least one minute) within 120 minutes of the start of infusion	120 minutes
Secondary	Evaluate the time to conversion to SR from start of infusion	Efficacy as measured by the time from the start of infusion to the time of conversion to SR for a duration of at least one minute	24 hours
Secondary	Evaluate the proportion of patients with sustained AF or late conversion to SR	Efficacy as measured by the proportion of patients with sustained or late conversion of AF of recent onset to SR at 12 hours, 24 hours and 7 days after start of infusion	12 hours, 24 hours and 7 days