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: Stable coronary artery disease (CAD)/chronic coronary syndrome; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2020-004455-32-FI
• Lead Sponsor: Imbria Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-12-11
• Last Update Posted: 8 January 2024

Recruitment & Eligibility

• Status: ot Recruiting
• 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 and =80 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.Patients 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=40% 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-H2O 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 2.3 mL/min/g
may be eligible for randomization after discussion with the Sponsor taking into account other factors (e.g. anatomic extent of inducible ischemia, angina severity, known inducible ischemia, angina severity, known inducible wall motion abnormalities on DSE).
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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Clinically significant LMS or proximal LAD stenosis likely to warrant or planned for
revascularization during the study period in the opinion of the investigator.
2.For those patients planned for FDG-PET imaging, patients under 50 years old and with Type 2 diabetes mellitus requiring regular insulin or diabetes that is sub-optimally controlled (i.e. HbA1c > 8% or 64 mmol/l)
3.Patients 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 inhibitor 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. Severe renal impairment defined as 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, despite medical therapy, uncontrolled 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 >40 kg/m2, or body mass >180 kg that precludes imaging procedures.
18.History of alcohol or drug abuse within the prior 2 years
19.Female patients who are pregnant, of child-bearing potential or who are currently breast-feeding.
20.Male patients with partners who are currently breast-feeding or women of child-bearing potential unable or unwilling to use condoms as a method of birth control for the duration of the study and until 90 days after the last dose of study drug
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.
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 patient and/or would interfere with the evaluation of the results or any other reasons that, in the opinion of the investigator, make the patient 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