Gene Therapy for Post-Operative Atrial Fibrillation

NCT05223725 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: WIRB1333791
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial will have 2 components: a brief dose-ranging study and a randomized comparison of 2 doses of AdKCNH2-G628S with control cardiac surgery patients. The study will assess safety of the intervention in a population at increased risk for post-operative atrial fibrillation.

Conditions

Atrial Fibrillation; Post-operative Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

• proportion of patients having a post-operative complication relative to controls

  proportion of patients having a post-operative complication relative to controls

  3 months

Secondary Outcomes (1)

• proportion of patients having post-operative atrial fibrillation

  1 month

Study Arms (4)

dose escalation

EXPERIMENTAL

initial phase, increasing dose

Biological: AdKCNH2-G628S

low dose

EXPERIMENTAL

second phase, fixed dose 5x10(11) vp

Biological: AdKCNH2-G628S

high dose

EXPERIMENTAL

second phase, fixed dose 2x10(12) vp

Biological: AdKCNH2-G628S

control

NO INTERVENTION

second phase, blinded, randomized with no intervention delivered but with testing and monitoring.

Interventions

AdKCNH2-G628S BIOLOGICAL

adenovirus containing the transgene KCNH2-G628S

dose escalation; high dose; low dose

Eligibility Criteria

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

You may qualify if:

• Elective valve surgery (alone or with coronary artery bypass grafting surgery) and one of the risk factors listed below, or elective coronary artery bypass grafting surgery with two of the risk factors listed below.
• Risk factors:
• age greater than 70,
• increased left atrial size (\> 4 cm left atrial diameter or LA volume index \> 35 on echocardiogram).
• obesity (body mass index \> 30)
• history of:
• paroxysmal AF
• hypertension
• chronic pulmonary disease
• diabetes mellitus
• clinical heart failure
• rheumatic heart disease

You may not qualify if:

• persistent or permanent AF
• QTc \> 475 on pre-op ECG or any time in last year (unless due to QT prolonging drug that was stopped \> 5 half-lives before surgery with verification of QT normalization after discontinuing drug)
• QTc prolonging drug use (unless stopped \> 5 half-lives prior to surgery)
• Any antiarrhythmic drug use in last year (inclusive of Vaughan Williams class I and III drugs, not including β-blocker or calcium channel blocker drugs)
• Any history of inherited arrhythmia syndrome
• Any prior or current sustained ventricular arrhythmias
• Any prior or current clinically significant bradyarrhythmias unless already treated with pacemaker and ventricular pacing \<20% (to reliable measure QT interval during the study)
• Any prior gene therapy
• Left ventricular ejection fraction (LVEF) \< 35%
• Prior open chest surgery
• History of or current malignancy, unless documented to be cured
• History of or current chemotherapy, radiotherapy, or other immunosuppressive therapy within the past 30 days. Corticosteroid treatment may be permitted at the discretion of the Primary Investigator
• History of infection with human immunodeficiency virus (HIV), hepatitis A, B, or C, or tuberculosis
• Immunizations of any kind in the month prior to surgery
• Underlying defect in immune function or history of multiple or severe life-threatening infections

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead

Study Sites (1)

UMass Memorial Hospital

Worcester, Massachusetts, 01655, United States

Location

Related Publications (3)

• Kikuchi K, McDonald AD, Sasano T, Donahue JK. Targeted modification of atrial electrophysiology by homogeneous transmural atrial gene transfer. Circulation. 2005 Jan 25;111(3):264-70. doi: 10.1161/01.CIR.0000153338.47507.83. Epub 2005 Jan 10.

  PMID: 15642761 BACKGROUND

• Amit G, Kikuchi K, Greener ID, Yang L, Novack V, Donahue JK. Selective molecular potassium channel blockade prevents atrial fibrillation. Circulation. 2010 Jun 1;121(21):2263-70. doi: 10.1161/CIRCULATIONAHA.109.911156. Epub 2010 May 17.

  PMID: 20479154 BACKGROUND

• Liu Z, Hutt JA, Rajeshkumar B, Azuma Y, Duan KL, Donahue JK. Preclinical efficacy and safety of KCNH2-G628S gene therapy for postoperative atrial fibrillation. J Thorac Cardiovasc Surg. 2017 Nov;154(5):1644-1651.e8. doi: 10.1016/j.jtcvs.2017.05.052. Epub 2017 May 23.

  PMID: 28676183 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

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

Study Officials

• Kevin Donahue, MD

  University of Massachusetts Chan Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: participant is masked due to delivery during general anesthesia, outcomes assessors and investigators are fully masked to study group.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: February 4, 2022
• Study Start: October 1, 2023
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2026
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: as per plan description
• Access Criteria: as per plan description

Locations

US (1)