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

NCT04680026 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HBI-3000-402
• Study Type: interventional
• Target: 150
• Locations: 5 countries
• Sites: 14

Brief 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.

Conditions

Atrial Fibrillation

Keywords

cardioversion

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (2)

• Evaluate the time to conversion to SR from start of infusion

  24 hours

• Evaluate the proportion of patients with sustained AF or late conversion to SR

  12 hours, 24 hours and 7 days

Study Arms (5)

Drug: HBI-3000, Stage A Dose Level 1

EXPERIMENTAL

Stage A Open Label HBI-3000 Dose Level 1: 200 mg

Drug: HBI-3000

Drug: HBI-3000, Stage A Dose Level 2

EXPERIMENTAL

Stage A Open Label HBI-3000 Dose Level 2: 350 mg planned

Drug: HBI-3000

Drug: HBI-3000, Stage A Dose Level 3

EXPERIMENTAL

Stage A Open Label HBI-3000 Dose Level 2: 500 mg planned

Drug: HBI-3000

Drug: HBI-3000, Stage B Dose Level 1

EXPERIMENTAL

Stage B Double-blind placebo controlled, Cohort 1 HBI-3000 Dose Level 1: Selected based on Stage A results

Drug: HBI-3000; Drug: Placebo

Drug: HBI-3000, Stage B Dose Level 2

EXPERIMENTAL

Stage B Double-blind placebo controlled, Cohort 2 HBI-3000 Dose Level 2: Selected based on Stage A, and Stage B Cohort 1 results

Drug: HBI-3000; Drug: Placebo

Interventions

HBI-3000 DRUG

Small molecule, multi-ion channel blocker

Also known as: sulcardine sulfate

Drug: HBI-3000, Stage A Dose Level 1; Drug: HBI-3000, Stage A Dose Level 2; Drug: HBI-3000, Stage A Dose Level 3; Drug: HBI-3000, Stage B Dose Level 1; Drug: HBI-3000, Stage B Dose Level 2

Placebo DRUG

Normal saline

Drug: HBI-3000, Stage B Dose Level 1; Drug: HBI-3000, Stage B Dose Level 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• HUYABIO International, LLC.: lead

Study Sites (14)

NCH Research Institute

Naples, Florida, 34102, United States

Location

Prairie Education & Research

Springfield, Illinois, 62701, United States

Location

North Mississippi Medical Center

Tupelo, Mississippi, 38801, United States

Location

CHRISTUS Trinity Mother Frances Hospital - Tyler

Tyler, Texas, 75701, United States

Location

University Clinical Center of the Republic of Srpska

Banja Luka, 78000, Bosnia and Herzegovina

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Centre hospitalier de L'Universite de Montral (CHUM)

Montreal, Quebec, H2X 0C1, Canada

Location

Centre integre de sante et de services sociaux de Lanaudiere - Hopital Pierre-Le Gardeur

Terrebonne, Quebec, J6V 2H2, Canada

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Wellington Regional Hospital

Wellington, 6021, New Zealand

Location

Niš University Clinical Center

Niš, Bulevar Doktora, 18108, Serbia

Location

University Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Dedinje Institute for Cardiovascular Diseases

Belgrade, 11040, Serbia

Location

University Hospital Medical Center Bezanijska kosa

Belgrade, 11080, Serbia

Location

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

sulcardine sulfate

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Allocation: Stage A: non-randomized; Stage B: randomized, double-blind and placebo-controlled Intervention Model: Two-stage study Masking: None; Stage A (open label); Stage B: randomized, double-blind and placebo-controlled

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 22, 2020
• Study Start: June 1, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: December 2, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); BO (1); CA (3); SE (4); NZ (2)