A Randomized, Participant- and Investigator-blinded, Sponsor Open-label, Placebo-controlled, Single and Multiple Dose Study to Investigate the Safety and Tolerability of XXB750 in Heart Failure Participants With Reduced or Mildly Reduced Ejection Fraction (HFrEF/HFmrEF)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 4
- 主要终点
- Adverse events, which may include abnormal vital signs, safety lab tests, or ECG parameters that induce clinical signs or symptoms, are considered clinically significant or require therapy
研究概览
简要总结
This is a multi-center, randomized, sponsor open-label, participant- and investigator-blinded, placebo-controlled, single and multiple dose study to investigate the safety and tolerability of XXB750 in HFrEF/HFmrEF.
详细描述
A screening period of up to 29 days will be used to assess participants' eligibility. This study will consist of 2 cohorts. Cohort 1 will include participants on stable therapies of ACEi/ARB and beta-blockers, in addition to other standard of care medications. Cohort 2 will consist of participants treated with sacubitril/valsartan and beta-blockers, in addition to other standard of care medications.
For Cohort 1 participants will be randomized in a 2:1 ratio to receive a single dose of subcutaneous (s.c) XXB750 or placebo. For Cohort 2, participants will be randomized in a 3:1 ratio to receive three doses of either s.c. XXB750 or placebo.
Cohort 1: After an initial domiciling period following study drug administration, participants will be followed for 13 weeks post-dosing for safety, tolerability and PK until the End of Study visit on Day 91.
Cohort 2: After a domiciling period following first study drug administration of XXB750 or placebo, participants will be followed for 27 days post dosing for safety, tolerability and PK. On Day 28, participants will be re domiciled and receive a second dose of either XXB750 or placebo. Participants will be followed for another 27 days post-dosing for safety and tolerability. On Day 56, participants will be re-domiciled and receive a third dose of either XXB750 or placebo. After the third domiciling period, participants will be followed for 13 weeks post-dosing for safety, tolerability and PK until the End of Study visit on Day 146.
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
- Double (Participant, Care Provider)
盲法说明
Site will have masked and unmasked investigators. An unmasked investigator will prepare and administer dose while a masked investigator will perform all assessments.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •NYHA functional class II-III
- •LVEF ≤ 50% documented at screening
- •Systolic blood pressure 110 - 160 mmHg (cohort 1) or 105-160 mmHg (cohort 2), and heart rate between 50-90 beats per minute, inclusive
- •Treatment with a stable dose of a beta blocker.
- •Cohort 1: Treatment with a stable dose of ACE inhibitor or ARB
- •Cohort 2: Treatment with a stable dose of sacubitril/valsartan.
- •Key Exclusion Criteria
- •Acute decompensated heart failure within 3 months prior to screening. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid, or other major cardiovascular surgery, PCI, or carotid angioplasty within the 6 months prior to screening
- •Hemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to LV dilatation at screening
- •Implantation of a CRT device within 3 months prior to screening or intent to implant a CRT during the study period
- •History of severe pulmonary disease (e.g. COPD) requiring chronic supplemental oxygen therapy or pulmonary hypertension requiring pharmacology treatment at Screening
- •eGFR <45 mL/min/1.73 m2 at screening
- •Cohort 1 only: Treatment with sacubitril/valsartan currently or within 4 weeks from screening
- •Cohort 2: Treatment with ACE inhibitor or ARB currently or within 4 weeks from screening
- •BMI >40 kg/m2
- •Other protocol-specific criteria may apply.
排除标准
- 未提供
研究组 & 干预措施
XXB750 Cohort 1
XXB750, single dose
干预措施: XXB750 (Drug)
Placebo Cohort 1
Placebo, single dose
干预措施: Placebo (Drug)
XXB750 Cohort 2
XXB750, multiple doses
干预措施: XXB750 (Drug)
Placebo Cohort 2
Placebo, multiple doses
干预措施: Placebo (Drug)
结局指标
主要结局
Adverse events, which may include abnormal vital signs, safety lab tests, or ECG parameters that induce clinical signs or symptoms, are considered clinically significant or require therapy
时间窗: 91 days (Cohort 1), 146 days (Cohort 2)
To evaluate the safety and tolerability of XXB750 in adult participants with chronic stable heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF).
次要结局
- Pharmacokinetics parameters CL/F(91 days (Cohort 1), 146 days (Cohort 2))
- Pharmacokinetics parameters T1/2(91 days (Cohort 1), 146 days (Cohort 2))
- Pharmacokinetics parameters AUCinf for Cohort 1(91 days)
- Pharmacokinetics parameters Vz/F(91 days (Cohort 1), 146 days (Cohort 2))
- Pharmacokinetics parameters Tmax(91 days (Cohort 1), 146 days (Cohort 2))
- Pharmacokinetics parameters AUCtau for Cohort 2(146 days)
- Pharmacokinetics parameters AUClast for Cohort 1(91 days)
- Pharmacokinetics parameters Cmax(91 days (Cohort 1), 146 days (Cohort 2))