AZD8601 Study in CABG Patients

NCT ID: NCT03370887

Last Updated: 2024-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-05
• Study Completion Date: 2021-06-30

Brief Summary

This is a randomized, double-blind, placebo-controlled, sequential design, multicentre study in patients with moderately impaired systolic function undergoing CABG surgery. Twenty four (24) patients scheduled for elective bypass surgery will be randomized (up to approximately 33 patients if replacements are needed). The objective is to investigate safety and tolerability of AZD8601 following epicardial injection in patients undergoing Coronary Artery Bypass Grafting (CABG) surgery with moderately impaired systolic function. At Visit 3 patients will receive either AZD8601 or placebo as epicardial injections and will then be followed up at 14 days (telephone visit) and 1, 3 and 6 months (on-site) post-surgery.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Low dose AZD8601 (3 mg)

8 patients will be randomised to receive 3 mg AZD8601

Group Type: EXPERIMENTAL

AZD8601

Intervention Type: DRUG

AZD8601 solution for injection, 0,5 mg/mL and 5 mg/mL will be given as 30 injections of 0.1 mg (3 mg per patient), or 1 mg (30 mg per patient) respectively on a single occasion

High dose AZD8601 (30 mg)

8 patients will be randomised to receive 30 mg AZD8601

Group Type: EXPERIMENTAL

AZD8601

Intervention Type: DRUG

AZD8601 solution for injection, 0,5 mg/mL and 5 mg/mL will be given as 30 injections of 0.1 mg (3 mg per patient), or 1 mg (30 mg per patient) respectively on a single occasion

Placebo

8 patients will be randomised to receive placebo injections

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo for AZ8601 injection for solution will be given as 30 injections per patient on a single occasion

Interventions

AZD8601

AZD8601 solution for injection, 0,5 mg/mL and 5 mg/mL will be given as 30 injections of 0.1 mg (3 mg per patient), or 1 mg (30 mg per patient) respectively on a single occasion

Intervention Type: DRUG

Placebo

Placebo for AZ8601 injection for solution will be given as 30 injections per patient on a single occasion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

For inclusion in the study patients should fulfil the following criteria at Visit 1 and/or 2:

1. Provision of signed and dated informed consent prior to any study specific procedures

Males and females:

1. Males must be surgically sterile or using an acceptable method of contraception

2. Females must be of non-childbearing potential confirmed at screening by fulfilling one of the following criteria a) postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the postmenopausal range, b) documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 3. Age >18 years 4. Indication for elective CABG surgery enrolled at least 15 days before the planned surgery 5. Moderately reduced global LVEF at rest (30% ≤ LVEF ≤ 50%) from medical records 6. If patient is on statin, ACE inhibitor/ARB, and/or beta-blocker, the dose should be stable at least 2 weeks prior to Visit 1 7. Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of AZD8601.

Exclusion Criteria

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2. Previous randomisation in the present study 3. Participation in another clinical study with an investigational product during the last 3 months 4. BMI > 35 kg/m2 OR poor image window for echocardiography 5. Need for CABG emergency operation. (Emergency operation is defined as significant symptom status worsening in CAD, such as crescendo angina, unstable angina or ACS requiring rescheduling the revascularization. CAD should be stable at least 3 months prior to Visit 3.) 6. History of ventricular arrhythmia (≥ Lown III) without Implantable Cardiac Defibrillator (ICD) History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study 8. Severe co-morbidities that can interfere with the execution of the study, interpretation of study results or affect the safety of the patient, in judgement of the investigator 9. eGFR ≤ 30 mL/min (derived from creatinine clearance, calculated by local lab) 10. For CFVR (Visit 1) and sMBF (Visit 2) measurement:

• Known severe adverse reactions to adenosine
• Known elevated intracranial pressure
• AV block ≥ second degree and/or sick sinus syndrome in patient without pacemaker
• Heart rate < 40 bpm (ECG verified)
• Systolic blood pressure < 90 mmHg
• Asthma or COPD with strong reactive component in judgement of investigator
• Treatment with dipyridamole (e.g. Persantin or Asasantin), theophyllamine or fluvoxamine that cannot be paused 11. Inability to comply with the protocol 12. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar chemical structure or class as study drugs 13. Patients unable to give their consent or communicate reliably with the investigator or vulnerable patients e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order 14. Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody or human immunodeficiency virus, at Visit 1 15. Known history of drug or alcohol abuse 16. Any concomitant medications that are known to be associated with Torsades de Pointes 17. History of QT prolongation associated with other medications that required discontinuation of that medication 18. Congenital long QT syndrome 19. History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3).

20. Current atrial fibrillation as well as paroxysmal atrial fibrillation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vesa Anttila, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Heart Center, Turku University, Finland

Locations

Research Site

New Haven, Connecticut, United States

Research Site

Kuopio, , Finland

Research Site

Tampere, , Finland

Research Site

Turku, , Finland

Research Site

München, , Germany

Research Site

München, , Germany

Research Site

Amsterdam, , Netherlands

Research Site

Groningen, , Netherlands

Research Site

Gothenburg, , Sweden

Research Site

Uppsala, , Sweden

Countries

United States; Finland; Germany; Netherlands; Sweden

References

Anttila V, Saraste A, Knuuti J, Hedman M, Jaakkola P, Laugwitz KL, Krane M, Jeppsson A, Sillanmaki S, Rosenmeier J, Zingmark P, Rudvik A, Garkaviy P, Watson C, Pangalos MN, Chien KR, Fritsche-Danielson R, Collen A, Gan LM. Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting. Mol Ther. 2023 Mar 1;31(3):866-874. doi: 10.1016/j.ymthe.2022.11.017. Epub 2022 Dec 17.

Reference Type: DERIVED

PMID: 36528793 (View on PubMed)

Anttila V, Saraste A, Knuuti J, Jaakkola P, Hedman M, Svedlund S, Lagerstrom-Fermer M, Kjaer M, Jeppsson A, Gan LM. Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial. Mol Ther Methods Clin Dev. 2020 Jun 1;18:464-472. doi: 10.1016/j.omtm.2020.05.030. eCollection 2020 Sep 11.

Reference Type: DERIVED

PMID: 32728595 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

D9150C00003

Identifier Type: -

Identifier Source: org_study_id