Principal Investigator: Vikas Sharma
Keywords: Atrial Fibrillation , Cardiac Surgery Department: Cardiothoracic Division
IRB Number: 00124130
Specialty: Cardiothoracic Surgery
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Margaret Carlson
margaret.carlson@hsc.utah.edu
8015853752

Brief Summary

POAF occurs at high rates despite standard-of-care therapies and is associated with problematic outcomes, eg, medical/procedural interventions, extended length of stay in the intensive care unit (ICU) and hospital, and rehospitalization. Non-clinical studies have demonstrated that injections of botulinum toxin type A into discrete regions of the heart can prevent AF and 2 clinical studies have demonstrated that botulinum toxin type A injections can prevent POAF with no noted safety issues.

This Phase 2, placebo-controlled study will evaluate the efficacy and safety of one-time injections of AGN-151607 125 U (25 U per fat pad) and 250 U (50 U per fat pad) distributed across each of the 5 major epicardial fat pads for the prevention of POAF in participants undergoing open-chest cardiac surgery. Injections will be administered during the open-chest cardiac surgery. Primary and secondary efficacy will be assessed for 30 days post-surgery; participants will be followed for additional efficacy and safety through Day 367 post-surgery.

Inclusion Criteria

1. Age

1.01 Participants must be 55 to 90 years of age, inclusive, at the time of signing the

informed consent.

2. Type of Participant and Surgical Characteristics

2.01 Participants who are scheduled to undergo open-chest cardiac surgery.

Includes: coronary artery bypass graft (CABG) and/or valve repair/replacement.

Inclusionary valve repair/replacement procedures for the primary reason for surgery

include:

 Aortic valve repair/replacement

 Mitral valve repair/replacement

 Combination of aortic and tricuspid valve repair/replacement

 Combination of mitral and tricuspid valve repair/replacement

 CABG/valve combination procedures (when valvular procedure is one of the

4 sub-bulleted procedures immediately above)

 Left Atrial Appendage (LAA) procedures are allowed if CABG and/or valve

repair or replacement is the qualifying surgical procedure, but is not a

qualifying surgical procedure on its own.

3. Sex

3.01 Male or female

4. Contraceptives

4.01 Male participants willing to minimize the risk of inducing pregnancy up to Day 60.

A male participant must agree to use contraception as detailed in Appendix 7,

Section 10.7 of this protocol until Day 60 and refrain from donating sperm during

this period.

4.02 Female participants willing to minimize the risk of inducing pregnancy up to

Day 60.

A female participant is eligible to participate if she is not pregnant (has a negative

urine pregnancy result prior to randomization) not breastfeeding, and at least 1 of the

following conditions applies:

a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 7,

Section 10.7

OR

b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 7,

Section 10.7 of this protocol until after Day 60.

5. Informed Consent

5.01 Capable of giving signed informed consent as described in Appendix 1,

Section 10.1, which includes compliance with the requirements and restrictions

listed in the informed consent form (ICF) and in this protocol.

5.02 Written informed consent from the participant has been obtained prior to any

study-related procedures.

5.03 Written documentation has been obtained in accordance with the relevant country

and local privacy requirements, where applicable (eg, Written Authorization for Use

and Release of Health and Research Study Information [US sites] and written Data

Protection consent (European Union [EU] sites).

6. Other

6.01 In sinus rhythm for the last 48 hours prior to randomization based on standard-of care

assessments and study ECGs (note: continuous ECG monitoring for 48 hours is

not required; prior history of paroxysmal AF is acceptable).

6.02 Willing to wear an ECG patch for a full 30 days post-surgery and for 7 days after

each study visit

6.03 Able, as assessed by the investigator, and willing to follow study instructions and

likely to complete required study visit.

Exclusion Criteria

1. Medical Conditions

1.01 Any uncontrolled clinically significant medical condition other than the one under study

that, in the investigator’s opinion, would put the participant at an unacceptable risk with

exposure to botulinum toxin type A.

1.02 Any medical condition that may put the participant at increased risk with exposure to

botulinum toxin type A, including diagnosed muscular dystrophy (eg, Duchenne’s

muscular dystrophy), myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral

sclerosis, mitochondrial disease, or any other significant disease which might interfere

with neuromuscular function.

1.03 Participants with presence or history of any of the following within 3 months prior to the

Day 1 visit that may indicate a vulnerable respiratory state per the investigator’s clinical

judgment: aspiration pneumonia, lower respiratory tract infections, uncontrolled asthma,

severe chronic obstructive pulmonary disease, or otherwise compromised respiratory

function.

1.04 Permanent/persistent AF

1.05 Has a known allergy or sensitivity to any botulinum toxin type A preparation

1.06 Has a known allergy or sensitivity to medical adhesive (eg, ECG patch adhesive;

hydrogel-based adhesive)

1.07 Severe (> 55 mm left atrial diameter) left atrial enlargement

1.08 Left ventricular ejection fraction (LVEF) < 25%

1.09 Presence or history of symptomatic atrioventricular block > 1st degree within the last

30 days (note: presence of a pacemaker is not exclusionary per se)

1.10 Exclusionary valve repair/replacement procedures include:

 Combination of aortic and mitral valve repair/replacement

 Isolated tricuspid valve repair/replacement

2. Prior/Concomitant Therapy

2.01 Class I or III antiarrhythmic drugs unless proper washout was documented

(Section 6.5.1)

2.02 Botulinum toxin type A (of any serotype) use within 6 months of randomization

2.03 Has been immunized for any botulinum toxin type A serotype as determined by

participant medical history

2.04 Preoperative need for inotropes/vasopressors or intra-aortic balloon pump

2.05 Prior open-chest, sternotomy cardiac surgery

2.06 History of ablation for AF

2.07 Planned ablation procedure for AF at the time of surgery

2.08 Emergency surgery

3. Prior/Concurrent Clinical Study Experience

3.01 Current enrollment in an investigational drug or device study or participation in such a

study within 30 days of entry into this study

4. Diagnostic Assessments

4.01 Participants have diagnostic assessments which in the opinion of the investigator prevent

participation in the study.

4.02 Impaired prognosis defined as EuroSCORE II > 7% perioperative mortality at screening

is exclusionary.

5. Other

5.01 Females who are pregnant, nursing, or planning a pregnancy during the study

5.02 The participant has a condition or is in a situation which, in the investigator’s opinion,

may put the participant at significant risk, may confound the study results, or may

interfere significantly with the participant’s participation in the study.