AZD8601 Study in CABG Patients

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03370887

Enrollment

Registered

2017-12-13

Start date

2018-02-05

Completion date

2021-06-30

Last updated

2024-10-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure

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.

Interventions

DRUGAZD8601

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

DRUGPlacebo

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

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 99 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Subjects With Adverse Events	From baseline to end of follow up at 6 months	—
Pulse Rate (Vital Sign)	From baseline to end of follow up at 6 months	—
Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant	From baseline to end of follow up at 6 months	—
Number of Subjects With High Values of Leukocytes, Particle Concentration	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Oxygen Saturation (Vital Sign)	From baseline to end of follow up at 6 months	—
Systolic Blood Pressure (Vital Sign)	From baseline to end of follow up at 6 months	—
Number of Subjects With High Values of Erythrocytes, Particle Concentration	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Diastolic Blood Pressure (Vital Sign)	From baseline to end of follow up at 6 months	—
Number of Subjects With High Values of Erythrocyte, Volume Fraction	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Erythrocytes, Mean Cell Volume	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Hemoglobin	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Neutrophils	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Lymphocytes	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Monocytes	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Eosinophils	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Basophils	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Platelets	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Reticulocytes	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Prothrombin Complex INR	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Activated Partial Thromboplastin Time	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Fibrinogen	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Sodium	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Potassium	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Urea	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Creatinine	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Albumin	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Calcium	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Phosphate	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Alkaline Phosphatase	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Alanine Aminotransferase	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Aspartate Aminotransferase	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.
Number of Subjects With High Values of Bilirubin, Total	From baseline to end of follow up at 6 months	Values are classified as high if they are above the normal reference range, based on local lab reference ranges.

Countries

Finland, Germany, Netherlands, Sweden, United States

Participant flow

Recruitment details

This study was conducted at 4 clinical research centers in Finland and Germany First subject enrolled (First subject first visit/first consent signed date): 2018. Last subject last visit: 2021.

Pre-assignment details

The study was to include two dose cohorts, which were to receive a total dose of 3 or 30 mg ofAZD8601. However, due to low recruitment levels, only 7 participants receiving a total dose of 3 mg AZD8601 and 4 participants receiving placebo completed dosing, according to the randomisation scheme

Participants by arm

Arm	Count
AZD8601 3mg AZD8601 3mg	7
Placebo Placebo	4
Total	11

Baseline characteristics

Characteristic	Placebo	Total	AZD8601 3mg
Age, Continuous	67.8 Years STANDARD_DEVIATION 10.8	68.1 Years STANDARD_DEVIATION 7.45	68.3 Years STANDARD_DEVIATION 5.8
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	4 Participants	11 Participants	7 Participants
Sex: Female, Male Female	2 Participants	2 Participants	0 Participants
Sex: Female, Male Male	2 Participants	9 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 7	0 / 4
other Total, other adverse events	7 / 7	4 / 4
serious Total, serious adverse events	3 / 7	1 / 4