A research study to determine the safety of IMB-1018972 and how it helps your heart use energy more efficiently to improve angina

Phase 1

Conditions: Coronary artery disease (CAD)
MedDRA version: 20.0Level: LLTClassification code 10028601Term: Myocardial ischemiaSystem Organ Class: 100000004849
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2020-004455-32-DK

Lead Sponsor: Imbria Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 65

Inclusion Criteria

1.Provide written informed consent before any screening procedures.
2.Able and willing to comply with all study procedures and requirements.
3.Male or female aged =35 years at screening
4.History of stable angina (CCS grading I-III) or anginal equivalent
within 12 months prior to screening
5.Regular use of at least 1 anti-anginal medication for symptomatic
treatment of angina (e.g. ß-blocker or calcium channel blocker) for at
least 2 weeks prior to start of dosing of study drug and likely to remain
on this therapy as background anti-anginal treatment at envisaged
stable doses for duration of study.
6.Subjects on regular beta blockade must be able to safely abstain from
beta blockers for 48 hours prior to DSE examinations in the opinion of
the Investigator.
7.LVEF= 45% by any imaging modality.
8. History (e.g. within past 5 years) of obstructive CAD or stress-induced
myocardial ischemia documented by any of the following:
• CT or invasive angiography demonstrating =50% diameter stenosis in
=1 major coronary artery OR in the setting of significant diffuse
atheroma
• Prior percutaneous coronary intervention (PCI)
• Prior coronary artery bypass graft (CABG) surgery
• PET myocardial perfusion imaging demonstrating MBF<2.4 mL/min/g
in =2 ischemic contiguous segments or involving =10.0% of the
myocardium(MBF must be <2.0 mL/min/g if it was obtained in the 3
months prior to screening)
• Stress echo or stress CMR demonstrating =2 ischemic contiguous
segments
• SPECT myocardial perfusion imaging demonstrating inducible
perfusion defect in =2 ischemic contiguous segments
9. Evaluable acoustic windows during contrast-enhanced, resting
echocardiography
10. Current 15O-H20 PET perfusion imaging demonstrating inducible
ischemia defined as hyperemic MBF<2.0 mL/min/g in =2 ischemic
contiguous segments and/or involving =10% of the myocardium.
Patients with a hyperemic MBF of 2.0 to 2.4 mL/min/g
may be eligible for randomization after discussion with the Sponsor

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 33
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion Criteria

1.Clinically significant LMS or proximal LAD stenosis likely to warrant
revascularization during the study period in the opinion of the
investigator
2.For those subjects planned for FDG-PET imaging, subjects with Type 2
diabetes mellitus requiring regular insulin or diabetes that is suboptimally
controlled (i.e. HbA1c > 8% or 64 mmol/l)
3.Subjects with Type 1 insulin dependent diabetes mellitus (IDDM)
4.Known allergy/intolerance/absolute contra-indication to trimetazidine
(TMZ), adenosine, dobutamine or atropine (e.g. glaucoma),
echocardiography contrast agent, or excipients of the IMP.
5.If any of the following have occurred:
•Any prior treatment with trimetazidine (TMZ)
•In the 4 months prior to screening:
i. NYHA functional class 3 or 4 HF
ii. CABG
•In the 2 months prior to screening:
i. acute coronary syndrome
ii. PCI
iii. stroke/TIA
•In the 1 month prior to screening, use of:
i. perhexiline
ii. meldonium
6.Ongoing treatment with heparin or heparin derivatives
7.SGLT2 and/or GLP-1 agonist therapy change (initiated or dose
changed) within 2 months prior to Visit 1
8.Presence of pacemaker, cardiac resynchronization therapy and/or
implantable cardioverter defibrillator
9. Severe valvular heart disease
10.eGFR < 30 ml/min/1.73 m2 (calculated by CKD-EPI).
11.ALT /AST and/or bilirubin > 2 x ULN at baseline
12.History of Parkinson's disease, Parkinsonian symptoms, or clinically
significant restless legs syndrome.
13. Exacerbating reversible medical cause for angina (e.g. severe anemia,
sustained hypertension defined as persistent BP > 160/90 mmHg,
hyperthyroidism).
14. Long QT duration at screening (QTcF duration >470 ms for males, and
>480 ms for females), or previously diagnosed long QT syndrome, or
first degree relative with diagnosed long QT syndrome.
15. Permanent atrial fibrillation (AF).
16. Left bundle branch block (LBBB)
17. BMI =18, or body mass >180 kg that precludes imaging procedures.
18. History of alcohol or drug abuse within the prior 2 years
19. Female subjects who are of child-bearing potential or who are
currently breast
feeding
20. Male subjects with female partners of child-bearing potential unable
and unwilling to
practice an approved method of birth control for the duration of the
study and until 90
days after the last dose of study drug (see section 6.3.1for approved
methods)
21. Any malignancy currently under active treatment (e.g. chemotherapy,
radiation). Patients with a history or concurrent malignancy may be
discussed on a case by case basis with the Sponsor. currently under
active treatment (e.g. chemotherapy,
radiation). Patients with a history or concurrent malignancy may be
discussed on a case by case basis with the Sponsor
22. Currently participating in or have participated in any other
investigational drug or implantable medical device trial within 3 months
prior to entry into this study.
23. Any major surgical procedure planned during the study period
24. Evidence of clinically significant renal, hepatic, hematological,
gastrointestinal, pulmonary, metabolic-endocrine, neurological,
urogenital or psychiatric disease that may constitute a health risk for the
subject and/or would interfere with the evaluation of the results or any
other reasons that, in the opinion of the investigator, make the subject
unsuitable for enrollment. Specifically, site specific requirements for
COVID must be followed

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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