Coronary Artery DiseasePhase 1/2EXACTNCT04125732
Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (The EXACT Trial)
A Phase 1/2 study testing AdVEGFXC1 in people with Coronary Artery Disease and Ischemia, run by XyloCor Therapeutics, Inc. at 16 sites in United States.
Trial summary
The primary purpose of this trial is to determine the safety of XC001 (AdVEGFXC1) in patients who suffer from angina caused by coronary artery disease and have no other treatment options. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Artery Disease, Ischemia, Angina Refractory
- What is being tested?
- AdVEGFXC1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 16 sitesUnited States
- Study dates
- 24 Jan 2020to 30 May 2023
- Phase
- Phase 1/2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females, age 18 to 80 years
- Diagnosis of chronic angina due to obstructive coronary artery disease that is refractory to drug therapy and unsuitable for revascularization via coronary artery bypass graft or percutaneous coronary intervention
- Angina class II-IV based on Canadian Cardiovascular Society Classification of Angina Pectoris
- Adequate hematologic (hemoglobin ≥ 10 g/dL, absolute neutrophil count > 1.2 × 10^3 per μL and platelet count ≥ 75,000 per μL), hepatic (alanine aminotransferase and aspartate aminotransferase ≤ 3 x ULN; total bilirubin ≤ 2 x ULN), and renal function (glomerular filtration rate > 29 mL/minute/1.73 m2)
- Adequate birth control if of child-bearing potential
- Must be willing and able to provide informed consent
Who cannot join
- ST elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI) not requiring revascularization, transmural myocardial infarction or cerebral vascular accident within the past 30 days
- New York Heart Association Function Class III or IV or left ventricular ejection fraction < 25% within the 6 weeks prior to the screening visit
- HbA1c ≥ 8.5%, SBP <90 or >180 mmHg, DBP >100 mmHg
- Other concurrent medical conditions that could jeopardize the safety of the subject or objectives of the study
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Lehigh Valley Health Network
Allentown, Pennsylvania, 18103
Emory University
Atlanta, Georgia, 30322
The Christ Hospital / The Lindner Research Center
Cincinnati, Ohio, 45219
University of Cincinnati
Cincinnati, Ohio, 45267
Cleveland Clinic
Cleveland, Ohio, 44195
The Ohio State University
Columbus, Ohio, 43210
Cardiology Research Associates
Daytona Beach, Florida, 32117
Duke University
Durham, North Carolina, 27710
University of Florida
Gainesville, Florida, 32610
Houston Methodist
Houston, Texas, 77030
Texas Heart Institute
Houston, Texas, 77030
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, 55407
University of Washington
Seattle, Washington, 98195
Stanford University
Stanford, California, 94305
James A. Haley VA Medical Center
Tampa, Florida, 33612
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase 1/2 Trial of Direct Administration of AdVEGF-All6A+, a Replication Deficient Adenovirus Vector Expressing a cDNA/Genomic Hybrid of Human VEGF, to the Ischemic Myocardium of Subjects With Angina Pectoris
The primary purpose of this trial is to determine the safety of XC001 (AdVEGFXC1) in patients who suffer from angina caused by coronary artery disease and have no other treatment options. Subjects in this study will receive one of four intramyocardial doses of XC001 that expresses human vascular endothelial growth factor (VEGF) which induces therapeutic angiogenesis (revascularization).
Read the detailed description
This is a Phase 1/2, first-in-human, multicenter, open-label, single arm dose escalation trial of XC001. Approximately 12 subjects (N=3 per cohort) who have refractory angina will be enrolled into 4 ascending dose groups, followed by an expansion of the highest tolerated dose with 32 additional subjects. XC001 will be administered by a transthoracic epicardial procedure. Safety will be the focus for the initial 6 months after XC001 administration followed by one safety focused telephone evaluation at Month 12.
- Conditions
- Coronary Artery Disease, Ischemia, Angina Refractory, Cardiovascular Diseases, Heart Diseases
- Being tested
- AdVEGFXC1
- Keywords
- Refractory angina, Coronary Artery Disease, Gene Therapy
- Medical subject headings
- Coronary Artery Disease, Ischemia, Cardiovascular Diseases, Heart Diseases, Angina Pectoris
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdVEGFXC1Biological
Also called XC001
AdVEGFXC1 at one of 4 doses
| Study group | Role | What they receive |
|---|---|---|
| AdVEGFXC1 at 1x10^9 vp | Experimental | Not described Receives: Biological: AdVEGFXC1 |
| AdVEGFXC1 at 1x10^10 vp | Experimental | Not described Receives: Biological: AdVEGFXC1 |
| AdVEGFXC1 at 4x10^10 vp | Experimental | Not described Receives: Biological: AdVEGFXC1 |
| AdVEGFXC1 at 1x10^11 vp | Experimental | Not described Receives: Biological: AdVEGFXC1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Endpoint (adverse events)
Safety, as assessed by adverse events and serious adverse events
Measured: 6 months
Secondary outcomes (4)
Secondary Endpoint (Exercise tolerance test)
Exercise tolerance test
Measured: 6 months
Secondary Endpoint (Seattle Angina Questionnaire)
Seattle Angina Questionnaire
Measured: 6 months
Secondary Endpoint (Canadian Cardiovascular Society angina class)
Canadian Cardiovascular Society angina class
Measured: 6 months
Secondary Endpoint (Angina episodes)
Angina episodes
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2019
- Study start24 Jan 2020
- Primary completion31 Jan 2023
- Study completion30 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- XyloCor Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04125732
- Sponsor's protocol ID
- XC001-1001
- Acronym
- EXACT
- Status last verified
- Jan 2024
- First submitted
- 4 Oct 2019
- Last updated
- 30 Jan 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stewart DJ, Hilton JD, Arnold JM, Gregoire J, Rivard A, Archer SL, Charbonneau F, Cohen E, Curtis M, Buller CE, Mendelsohn FO, Dib N, Page P, Ducas J, Plante S, Sullivan J, Macko J, Rasmussen C, Kessler PD, Rasmussen HS. Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment. Gene Ther. 2006 Nov;13(21):1503-11. doi: 10.1038/sj.gt.3302802. Epub 2006 Jun 22.
PubMed 16791287Nakamura K, Henry TD, Traverse JH, Latter DA, Mokadam NA, Answini GA, Williams AR, Sun BC, Burke CR, Bakaeen FG, DiCarli MF, Chaitman BR, Peterson MW, Byrnes DG, Ohman EM, Pepine CJ, Crystal RG, Rosengart TK, Kowalewski E, Koch GG, Dittrich HC, Povsic TJ; EXACT Trial Investigators. Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial. Circ Cardiovasc Interv. 2024 May;17(5):e014054. doi: 10.1161/CIRCINTERVENTIONS.124.014054. Epub 2024 May 2.
PubMed 38696284Povsic TJ, Henry TD, Traverse JH, Anderson RD, Answini GA, Sun BC, Arnaoutakis GJ, Boudoulas KD, Williams AR, Dittrich HC, Tarka EA, Latter DA, Ohman EM, Peterson MW, Byrnes D, Pepine CJ, DiCarli MF, Crystal RG, Rosengart TK, Mokadam NA. EXACT Trial: Results of the Phase 1 Dose-Escalation Study. Circ Cardiovasc Interv. 2023 Aug;16(8):e012997. doi: 10.1161/CIRCINTERVENTIONS.123.012997. Epub 2023 Jul 28.
PubMed 37503661Povsic TJ, Henry TD, Ohman EM, Pepine CJ, Crystal RG, Rosengart TK, Reinhardt RR, Dittrich HC, Traverse JH, Answini GA, Mokadam NA. Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations. Am Heart J. 2021 Nov;241:38-49. doi: 10.1016/j.ahj.2021.06.013. Epub 2021 Jul 2.
PubMed 34224684
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Trial of Direct Administration of AdVEGF-All6A+, a Replication Deficient Adenovirus Vector Expressing a cDNA/Genomic Hybrid of Human VEGF, to the Ischemic Myocardium of Subjects With Angina Pectoris
- ClinicalTrials.gov ID
- NCT04125732
- Acronym / sponsor ID
- EXACT / XC001-1001
- Conditions
- Coronary Artery Disease, Ischemia, Angina Refractory, Cardiovascular Diseases, Heart Diseases
- Keywords
- Refractory angina, Coronary Artery Disease, Gene Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- XyloCor Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Jan 2020 (actual)
- Primary completion
- 31 Jan 2023 (actual)
- Study completion
- 30 May 2023 (actual)
- First posted
- 14 Oct 2019 (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.
The primary purpose of this trial is to determine the safety of XC001 (AdVEGFXC1) in patients who suffer from angina caused by coronary artery disease and have no other treatment options. Subjects in this study will receive one of four intramyocardial doses of XC001 that expresses human vascular endothelial growth factor (VEGF) which induces therapeutic angiogenesis (revascularization).
Detailed description
This is a Phase 1/2, first-in-human, multicenter, open-label, single arm dose escalation trial of XC001. Approximately 12 subjects (N=3 per cohort) who have refractory angina will be enrolled into 4 ascending dose groups, followed by an expansion of the highest tolerated dose with 32 additional subjects. XC001 will be administered by a transthoracic epicardial procedure. Safety will be the focus for the initial 6 months after XC001 administration followed by one safety focused telephone evaluation at Month 12.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AdVEGFXC1 at 1x10^9 vp | Experimental | Biological: AdVEGFXC1 |
| AdVEGFXC1 at 1x10^10 vp | Experimental | Biological: AdVEGFXC1 |
| AdVEGFXC1 at 4x10^10 vp | Experimental | Biological: AdVEGFXC1 |
| AdVEGFXC1 at 1x10^11 vp | Experimental | Biological: AdVEGFXC1 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Males and females, age 18 to 80 years
- Diagnosis of chronic angina due to obstructive coronary artery disease that is refractory to drug therapy and unsuitable for revascularization via coronary artery bypass graft or percutaneous coronary intervention
- Angina class II-IV based on Canadian Cardiovascular Society Classification of Angina Pectoris
- Adequate hematologic (hemoglobin ≥ 10 g/dL, absolute neutrophil count > 1.2 × 10^3 per μL and platelet count ≥ 75,000 per μL), hepatic (alanine aminotransferase and aspartate aminotransferase ≤ 3 x ULN; total bilirubin ≤ 2 x ULN), and renal function (glomerular filtration rate > 29 mL/minute/1.73 m2)
- Adequate birth control if of child-bearing potential
Key exclusion criteria (4 listed)
- ST elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI) not requiring revascularization, transmural myocardial infarction or cerebral vascular accident within the past 30 days
- New York Heart Association Function Class III or IV or left ventricular ejection fraction < 25% within the 6 weeks prior to the screening visit
- HbA1c ≥ 8.5%, SBP <90 or >180 mmHg, DBP >100 mmHg
- Other concurrent medical conditions that could jeopardize the safety of the subject or objectives of the study
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 |
|---|---|---|
| AdVEGFXC1Also: XC001AdVEGFXC1 at one of 4 doses | Biological | AdVEGFXC1 at 1x10^10 vp, AdVEGFXC1 at 1x10^11 vp, AdVEGFXC1 at 1x10^9 vp, AdVEGFXC1 at 4x10^10 vp |
Primary outcome
Primary Endpoint (adverse events)
Time frame: 6 months
Safety, as assessed by adverse events and serious adverse events
4 secondary outcomes
Secondary Endpoint (Exercise tolerance test)
Time frame: 6 months
Secondary Endpoint (Seattle Angina Questionnaire)
Time frame: 6 months
Secondary Endpoint (Canadian Cardiovascular Society angina class)
Time frame: 6 months
Secondary Endpoint (Angina episodes)
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2024.
- Background: PubMed 16791287Stewart DJ, Hilton JD, Arnold JM, Gregoire J, Rivard A, Archer SL, Charbonneau F, Cohen E, Curtis M, Buller CE, Mendelsohn FO, Dib N, Page P, Ducas J, Plante S, Sullivan J, Macko J, Rasmussen C, Kessler PD, Rasmussen HS. Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment. Gene Ther. 2006 Nov;13(21):1503-11. doi: 10.1038/sj.gt.3302802. Epub 2006 Jun 22.
- Derived from this study: PubMed 38696284Nakamura K, Henry TD, Traverse JH, Latter DA, Mokadam NA, Answini GA, Williams AR, Sun BC, Burke CR, Bakaeen FG, DiCarli MF, Chaitman BR, Peterson MW, Byrnes DG, Ohman EM, Pepine CJ, Crystal RG, Rosengart TK, Kowalewski E, Koch GG, Dittrich HC, Povsic TJ; EXACT Trial Investigators. Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial. Circ Cardiovasc Interv. 2024 May;17(5):e014054. doi: 10.1161/CIRCINTERVENTIONS.124.014054. Epub 2024 May 2.
- Derived from this study: PubMed 37503661Povsic TJ, Henry TD, Traverse JH, Anderson RD, Answini GA, Sun BC, Arnaoutakis GJ, Boudoulas KD, Williams AR, Dittrich HC, Tarka EA, Latter DA, Ohman EM, Peterson MW, Byrnes D, Pepine CJ, DiCarli MF, Crystal RG, Rosengart TK, Mokadam NA. EXACT Trial: Results of the Phase 1 Dose-Escalation Study. Circ Cardiovasc Interv. 2023 Aug;16(8):e012997. doi: 10.1161/CIRCINTERVENTIONS.123.012997. Epub 2023 Jul 28.
- Derived from this study: PubMed 34224684Povsic TJ, Henry TD, Ohman EM, Pepine CJ, Crystal RG, Rosengart TK, Reinhardt RR, Dittrich HC, Traverse JH, Answini GA, Mokadam NA. Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations. Am Heart J. 2021 Nov;241:38-49. doi: 10.1016/j.ahj.2021.06.013. Epub 2021 Jul 2.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AdVEGFXC1 in people with Coronary Artery Disease and Ischemia, run by XyloCor Therapeutics, Inc. at 16 sites 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 6 inclusion and 4 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: finished, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Primary Endpoint (adverse events) (time frame: 6 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 NCT04125732, which also lists 4 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 30 Jan 2024.