A Study to Evaluate the Safety, Tolerability, and Efficacy of IMB-1018972 in Patients With Refractory Angina

Inclusion Criteria

• •1. Is between the ages of 18 and 85 years, inclusive.
• •2. Is capable of understanding the written informed consent, and providing signed, dated, and witnessed written informed consent.
• •3. Has complied with and is willing to continue to comply with the specified procedures (eg, angina diary during screening) and complete specific follow-up evaluations.
• •4. Has coronary artery disease confirmed by at least one of the following:
• •* Documented prior MI, CABG surgery, or PCI -OR-
• •* Angiography performed within the 24 months prior to Visit 1 confirming CAD (eg, evidence of ≥70% stenosis of at least one major coronary artery or diffuse CAD).
• •5. Has evidence of stress induced ischemia documented by either:
• •* Protocol-specified ETT ECG demonstrating at least 0.5 mm exercise-induced ST segment depression with onset \<9 minutes on at least 1 of the screening ETTs -OR-
• •* Prior evidence of stress-induced reversible perfusion defect in the last 24 months (without intervening revascularization) identified by at least one of the following:
• •* Radionuclide imaging study
• •* Echocardiographic imaging study
• •* FFR \<0.8
• •* IFR \<0.89
• •* FFR CT \<0.8
• •* CFR \<2.5
• •6. Has a minimum 3 month history of exertional angina, including angina with a minimum frequency of 2 anginal episodes per week on average for the 2 weeks prior to enrolling in the study while on optimal guideline directed medical therapy for their angina.
• •7. Is on optimal, dual agent, antianginal therapy for their angina for at least 1 month prior to the first screening ETT. Consistent with ACC/AHA and ESC Class I guideline directed medical therapy (GDMT), criteria for optimal therapy include treatment with both: (a) a beta-adrenergic blocking agent and treatment with (b) a calcium channel blocker OR a long-acting nitrate. If unacceptable side effects are intolerable and documented with a therapy listed in (a) or (b), treatment with only 1 antianginal medication is acceptable. Additionally, patients should be treated with short-acting nitrates per GDMT.
• •8. Is currently not clinically indicated for coronary revascularization (ie, PCI or CABG) in the opinion of the principle investigator at the time of screening through 6 months after randomization.
• •9. Has a CCS score of II, III or stabilized IV for 1 month prior to screening.
• •10. Meets the following requirements after 2 screening modified Bruce protocol ETTs:
• •a. Stopping the treadmill test due to angina on each test b. Total exercise duration must fall between 3 and 9 minutes on each test c. To document inducible myocardial ischemia: i. For those patients with interpretable ECGs, at least 0.5 mm exercise induced ST segment depression must occur with onset \<9 minutes on at least 1 of the screening ETTs.
• •d. Difference in TED between the 2 qualifying ETTs must not exceed 20% of the longer test or 1 minute, whichever limit is smaller.
• •e. Consideration of a third ETT may be discussed by the investigator with the study medical monitor, who may authorize the performance of a third ETT a minimum of 5 days and no more than 10 days after the second ETT