Atrial FibrillationPhase 1AFGT01NCT05223725
Gene Therapy for Post-Operative Atrial Fibrillation
A Phase 1 study testing AdKCNH2-G628S in people with Atrial Fibrillation and Post-operative Atrial Fibrillation, run by University of Massachusetts, Worcester at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Post-operative Atrial Fibrillation
- What is being tested?
- AdKCNH2-G628S
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2023to Aug 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- paroxysmal AF
- hypertension
- chronic pulmonary disease
- diabetes mellitus
- clinical heart failure
- rheumatic heart disease
Who cannot join
- 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
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- 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
- Significant liver disease (active hepatitis, AST or ALT greater than twice the upper limit of normal, prior or current liver failure with Pugh-Child category A-C disease)
- Significant renal disease (GFR less than 30)
- Current pregnancy
- Childbearing potential unless participant agrees to prevent pregnancy prior to and for at least 3 months after virus delivery 10
- Any condition that limits life to < 12 months other than the condition to be treated with the planned surgery
- Participation in any other clinical trial within 30 days of surgery
- Incarcerated persons
- Individuals under the age of 18 years
- Unwillingness to undergo the study interventions and follow-up as outlined in the schedule of events
- Ongoing medical or other condition that is deemed by the Principal Investigator to interfere with the conduct or assessments of the study
- Lack of capacity to provide participant's own informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
UMass Memorial Hospital
Worcester, Massachusetts, 01655
About this study
Official title: AdKCNH2-G628S Gene Therapy for Post-Operative Atrial Fibrillation
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.
Read the detailed description
Post-operative AF (POAF) is a specific form of AF occurring in the days after cardiothoracic surgery. A unique element of POAF is the limited duration of risk, which peaks 3 days and dissipates 10 days after surgery. We propose gene therapy for POAF. Our hypothesis is that counteracting AF-related electrical remodeling will disrupt the reentrant electrical circuits integral to maintaining AF. We have extensive preclinical data showing safety and efficacy of adenoviral gene transfer using the gene mutation KNCH2-G628S. When delivered to the atria using adenoviruses and a novel gene painting technique, KCNH2-G628S effectively and specifically prolongs atrial action potential and prevents development of AF for the 10-14-day duration of post-operative AF risk. 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.
- Being tested
- AdKCNH2-G628S
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdKCNH2-G628SBiological
adenovirus containing the transgene KCNH2-G628S
| Study group | Role | What they receive |
|---|---|---|
| dose escalation | Experimental | initial phase, increasing dose Receives: Biological: AdKCNH2-G628S |
| low dose | Experimental | second phase, fixed dose 5x10(11) vp Receives: Biological: AdKCNH2-G628S |
| high dose | Experimental | second phase, fixed dose 2x10(12) vp Receives: Biological: AdKCNH2-G628S |
| control | No intervention | second phase, blinded, randomized with no intervention delivered but with testing and monitoring. |
What is being measured
The primary outcome is the main question the study is designed to answer.
proportion of patients having a post-operative complication relative to controls
proportion of patients having a post-operative complication relative to controls
Measured: 3 months
Secondary outcomes (1)
proportion of patients having post-operative atrial fibrillation
proportion of patients having post-operative atrial fibrillation
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2022
- Study start1 Oct 2023
- Primary completionAug 2025 (estimated)
- Study completionAug 2026 (estimated)
Why it stopped: Problems with receiving investigational agent and problems with funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by University of Massachusetts, WorcesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Massachusetts, Worcester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kevin Donahue, MD, Principal investigator, University of Massachusetts, Worcester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05223725
- Sponsor's protocol ID
- WIRB1333791
- Acronym
- AFGT01
- Status last verified
- Mar 2025
- First submitted
- 24 Jan 2022
- Last updated
- 1 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data from the clinical trial will be made available to the scientific community and the general public in the following ways: 1. As soon as final data are complete, verified and analyzed, manuscripts will be written and submitted to scientific journals with the highest possible impact factor to achieve the widest possible dissemination within the scientific community. 2. Presentations at scientific meetings within the disciplines of cardiac surgery, cardiology, cardiac electrophysiology and gene therapy will further disseminate the research information gained as a result of the proposed studies. 3. The research data will be uploaded to an openly available research website maintained by UMass for review and use by the scientific community. 4. The research results will be uploaded to clinicaltrials.gov. 5. Press releases, summaries of research findings and interviews with investigators will be released to the general public to publicize the information gained in the proposed research.
Publications
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.
PubMed 15642761Amit 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.
PubMed 20479154Liu 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.
PubMed 28676183
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AdKCNH2-G628S Gene Therapy for Post-Operative Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT05223725
- Acronym / sponsor ID
- AFGT01 / WIRB1333791
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Problems with receiving investigational agent and problems with funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Massachusetts, WorcesterUniversity, hospital or other
- Study start
- 1 Oct 2023 (actual)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 4 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Post-operative AF (POAF) is a specific form of AF occurring in the days after cardiothoracic surgery. A unique element of POAF is the limited duration of risk, which peaks 3 days and dissipates 10 days after surgery. We propose gene therapy for POAF. Our hypothesis is that counteracting AF-related electrical remodeling will disrupt the reentrant electrical circuits integral to maintaining AF. We have extensive preclinical data showing safety and efficacy of adenoviral gene transfer using the gene mutation KNCH2-G628S. When delivered to the atria using adenoviruses and a novel gene painting technique, KCNH2-G628S effectively and specifically prolongs atrial action potential and prevents development of AF for the 10-14-day duration of post-operative AF risk. 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| dose escalation | Experimental | Biological: AdKCNH2-G628Sinitial phase, increasing dose |
| low dose | Experimental | Biological: AdKCNH2-G628Ssecond phase, fixed dose 5x10(11) vp |
| high dose | Experimental | Biological: AdKCNH2-G628Ssecond phase, fixed dose 2x10(12) vp |
| control | No intervention | –second phase, blinded, randomized with no intervention delivered but with testing and monitoring. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdKCNH2-G628Sadenovirus containing the transgene KCNH2-G628S | Biological | dose escalation, high dose, low dose |
Primary outcome
proportion of patients having a post-operative complication relative to controls
Time frame: 3 months
proportion of patients having a post-operative complication relative to controls
1 secondary outcome
proportion of patients having post-operative atrial fibrillation
Time frame: 1 month
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
- Background: PubMed 15642761Kikuchi 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.
- Background: PubMed 20479154Amit 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.
- Background: PubMed 28676183Liu 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.
- Individual participant dataSharing planned: Yes. Data from the clinical trial will be made available to the scientific community and the general public in the following ways: 1. As soon as final data are complete, verified and analyzed, manuscripts will be written and submitted to scientific journals with the highest possible impact factor to achieve the widest possible dissemination within the scientific community. 2. Presentations at scientific meetings within the disciplines of cardiac surgery, cardiology, cardiac electrophysiology and gene therapy will further disseminate the research information gained as a result of the proposed studies. 3. The research data will be uploaded to an openly available research website maintained by UMass for review and use by the scientific community. 4. The research results will be uploaded to clinicaltrials.gov. 5. Press releases, summaries of research findings and interviews with investigators will be released to the general public to publicize the information gained in the proposed research.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Donahue, MD principal investigator
University of Massachusetts, Worcester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AdKCNH2-G628S in people with Atrial Fibrillation and Post-operative Atrial Fibrillation, run by University of Massachusetts, Worcester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
proportion of patients having a post-operative complication relative to controls (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05223725, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2025.