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AZD8601 Study in CABG Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03370887
Recruitment Status : Recruiting
First Posted : December 13, 2017
Last Update Posted : November 5, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE November 16, 2017
First Posted Date  ICMJE December 13, 2017
Last Update Posted Date November 5, 2020
Actual Study Start Date  ICMJE February 5, 2018
Estimated Primary Completion Date January 27, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2017)
  • Serious Adverse Events [ Time Frame: Up to 9 months; from signing of ICF at Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP. ]
    To assess safety and tolerability of AZD8601 given as epicardial injections
  • Adverse event [ Time Frame: 6 months, from receiving IP at Visit 3 until 6 months after receiving IP. ]
    To assess safety and tolerability of AZD8601 given as epicardial injections
  • Electrocardiogram (ECG, number of patients with ECG results exceeding ICH reference ranges) [ Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP. ]
    To assess safety and tolerability of AZD8601 given as epicardial injections
  • Left ventricular ejection fraction (LVEF) change from baseline (%) [ Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP. ]
    To assess safety and tolerability of AZD8601 given as epicardial injections
  • Changes in physical examination (number of abnormal findings in physical examination) [ Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP. ]
    To assess safety and tolerability of AZD8601 given as epicardial injections
  • Changes in vital signs - blood pressure (mmHg) [ Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP. ]
    To assess safety and tolerability of AZD8601 given as epicardial injections
  • Changes in vital signs - pulse (bpm) [ Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP. ]
    To assess safety and tolerability of AZD8601 given as epicardial injections
  • Changes in laboratory values - hematology [ Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP. ]
    To assess safety and tolerability of AZD8601 given as epicardial injections
  • Changes in laboratory values - clinical chemistry [ Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP. ]
    To assess safety and tolerability of AZD8601 given as epicardial injections
  • Changes in laboratory values - urinalysis [ Time Frame: Up to 9 months; from Visit 1, maximum 90 days before investigational product (IP) administration, until 6 months after receiving IP. ]
    To assess safety and tolerability of AZD8601 given as epicardial injections
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AZD8601 Study in CABG Patients
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Multi-centre, Sequential Design, Phase IIa Study to Evaluate Safety and Tolerability of Epicardial Injections of AZD8601 During Coronary Artery Bypass Grafting Surgery
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Heart Failure
Intervention  ICMJE
  • Drug: 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
  • Drug: Placebo
    Placebo for AZ8601 injection for solution will be given as 30 injections per patient on a single occasion
Study Arms  ICMJE
  • Experimental: Low dose AZD8601 (3 mg)
    8 patients will be randomised to receive 3 mg AZD8601
    Intervention: Drug: AZD8601
  • Experimental: High dose AZD8601 (30 mg)
    8 patients will be randomised to receive 30 mg AZD8601
    Intervention: Drug: AZD8601
  • Placebo Comparator: Placebo
    8 patients will be randomised to receive placebo injections
    Intervention: Drug: Placebo
Publications * Anttila V, Saraste A, Knuuti J, Jaakkola P, Hedman M, Svedlund S, Lagerström-Fermér 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 16, 2020)
24
Original Estimated Enrollment  ICMJE
 (submitted: December 6, 2017)
33
Estimated Study Completion Date  ICMJE January 27, 2023
Estimated Primary Completion Date January 27, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Finland,   Germany,   Netherlands,   Sweden
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT03370887
Other Study ID Numbers  ICMJE D9150C00003
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Vesa Anttila, MD, PhD Heart Center, Turku University, Finland
PRS Account AstraZeneca
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP