Status:
WITHDRAWN
A Study to Evaluate the Safety, Tolerability, and Efficacy of IMB-1018972 in Patients With Refractory Angina
Lead Sponsor:
Imbria Pharmaceuticals, Inc.
Conditions:
Refractory Angina
Eligibility:
All Genders
18-85 years
Phase:
PHASE2
Brief Summary
The objectives of the study are to assess the safety, tolerability, and potential efficacy of IMB-1018972 on patients with refractory angina. Study will assess functional capacity employing a modified...
Eligibility Criteria
Inclusion
- Is between the ages of 18 and 85 years, inclusive.
- Is capable of understanding the written informed consent, and providing signed, dated, and witnessed written informed consent.
- 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.
- 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).
- 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
- 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.
- 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.
- 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.
- Has a CCS score of II, III or stabilized IV for 1 month prior to screening.
- 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
Exclusion
- If any of the following have occurred:
- Use of TMZ anytime in prior history
- In the prior 6 months:
- Diagnosis of NYHA Class 3 or 4 (heart failure)
- Hospitalization for heart failure
- Coronary artery bypass graft surgery
- Cardiac resynchronization therapy placement or adjustments to CRT parameters
- Implantable cardioverter defibrillator or biventricular pacemaker placement
- In the prior 3 months:
- Hospitalization for a cardiovascular indication
- Cerebral vascular accident
- Transient ischemic attack
- Percutaneous coronary intervention
- In the prior 1 month:
- Use of perhexiline or meldonium.
- Has a history of moderate to severe valvular heart disease defined as aortic stenosis (valve area \<1.5 cm2), aortic insufficiency, mitral stenosis (valve area \<1.5 cm2), or mitral valve regurgitation of grade 3 or worse.
- Has significant hepatic disease, with increased liver function tests such as total bilirubin, aspartate aminotransferase, or alanine aminotransferase more than 2 times of ULN at baseline (excluding patients with documented history of Gilbert syndrome).
- Has severe renal impairment (ie, creatinine clearance \<30 mL/min at screening, measured using 4-variable modification of diet in renal disease equation).
- Has a history of Parkinson disease, Parkinsonian symptoms, tremors, restless leg syndrome, or other related movement disorders.
- Has a history of vasospastic angina or microvascular angina.
- Has an exacerbating cause for angina (eg, anemia \[ie, hemoglobin \<10 g/dL\], uncontrolled hypertension \[ie, BP ≥160/90 mmHg\], hyperthyroid, or rapid AF \[ie, AF with average rate \>120 beats per minute\]) at screening.
- Has long-QT and life-threatening LV arrhythmia.
- Has comorbidities limiting life expectancy to less than 3 years.
- Is pregnant, planning pregnancy, or lactating.
- Has a history of alcohol abuse or drug addiction.
- Has a positive test for drugs (eg, opiates, methadone, cocaine, amphetamines \[including ecstasy\], or barbiturates) at screening.
- Has a positive test for HBsAg, HCV antibodies, or HIV1/2 antibodies at screening.
- Is participating in another research study.
- Is an employee or family member of the investigator or study site personnel.
Key Trial Info
Start Date :
May 1 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 1 2025
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT04306237
Start Date
May 1 2020
End Date
April 1 2025
Last Update
November 10 2025
Active Locations (1)
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1
Imbria Investigational Site
Boston, Massachusetts, United States, 02110