NCT04306237撤回2 期
A Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of IMB-1018972 in Patients With Refractory Angina
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 640
- 试验地点
- 1
- 主要终点
- Modified Bruce Protocol Treadmill ETT
研究概览
简要总结
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 Bruce Protocol treadmill ETT, patient reports of angina symptoms via an electronic diary, and activity using an accelerometer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
IMB-1018972
Experimental
Participants will receive IMB-1018972 (200 mg) MR tablets twice daily for 16 weeks
干预措施: IMB-1018972 (Drug)
Placebo
Placebo Comparator
Participants will receive matching placebo tablets twice daily for 16 weeks
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Modified Bruce Protocol Treadmill ETT
时间窗: 8 weeks
Change from baseline to Week 8 in total exercise duration (seconds)
Safety and Tolerability of IMB-1018972 in Patients with Refractory Angina
时间窗: 16 weeks
Incidence of AEs, changes from baseline in physical examinations, vital signs, clinical laboratories, and ECG
次要结局
- Assess the benefit of IMB-1018972 on patient report of angina symptoms employing an electronic diary(16 weeks)
- Assess the potential treatment benefit of IMB-1018972 on patient activity employing a wearable device(16 weeks)
- Assess the potential treatment benefit of IMB-1018972 on patient report of rescue NTG use employing an electronic diary(16 weeks)
研究者
研究点 (1)
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