Clinical trial NCT04680026: A Study of IV HBI-3000 for the Conversion Recent Onset Atrial Fibrillation (AF)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Atrial Fibrillation
Keywords: cardioversion
Lead sponsor: HUYABIO International, LLC.
Sponsor class: INDUSTRY
First posted: 2020-12-22
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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.

Detailed 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.

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

Primary outcomes:
measure: 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)
timeFrame: 30 days
measure: 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)
timeFrame: 90 minutes
measure: 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)
timeFrame: 90 minutes
measure: 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
timeFrame: 24 hours
measure: The efficacy of intravenously (IV) administered HBI-3000 as measured by the proportion of patients with AF of recent onset who convert to SR
timeFrame: 120 minutes
Secondary outcomes:
measure: Evaluate the time to conversion to SR from start of infusion
timeFrame: 24 hours
measure: Evaluate the proportion of patients with sustained AF or late conversion to SR
timeFrame: 12 hours, 24 hours and 7 days
Other outcomes:
Locations:
city: Naples
country: United States
facility: NCH Research Institute
state: Florida
city: Springfield
country: United States
facility: Prairie Education & Research
state: Illinois
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Tyler
country: United States
facility: CHRISTUS Trinity Mother Frances Hospital - Tyler
state: Texas
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Center of the Republic of Srpska
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montréal
country: Canada
facility: Centre hospitalier de L'Universite de Montral (CHUM)
state: Quebec
city: Terrebonne
country: Canada
facility: Centre integre de sante et de services sociaux de Lanaudiere - Hopital Pierre-Le Gardeur
state: Quebec
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Wellington
country: New Zealand
facility: Wellington Regional Hospital
city: Niš
country: Serbia
facility: Niš University Clinical Center
state: Bulevar Doktora
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Dedinje Institute for Cardiovascular Diseases
city: Belgrade
country: Serbia
facility: University Hospital Medical Center Bezanijska kosa
Study officials:
References: