A First-in-Human Phase 1/2 Study of ABCL635 in Healthy Participants and in Postmenopausal Women With Moderate-to-Severe Vasomotor Symptoms
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 136
- 试验地点
- 18
- 主要终点
- Frequency and severity of adverse events (AE)
研究概览
简要总结
The purpose of this study is to evaluate the effects of single and multiple doses of ABCL635 administered by subcutaneous (SC) injection to healthy men and to postmenopausal women with or without any vasomotor symptoms (VMS) or hot flashes, and to postmenopausal women with moderate-to-severe VMS associated with menopause. The safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) parameters of ABCL635 will be assessed in all study participants; the effects on frequency and severity of VMS will be assessed in postmenopausal women who experience moderate-to-severe symptoms.
详细描述
The study consists of 3 parts: Part A and Part B (Phase 1) and Part C (Phase 2). In Part A, single ascending doses (SAD) of ABCL635 or placebo will be administered to healthy male and female participants. In Part B, up to 3 multiple ascending doses (MAD) of ABCL635 or placebo will be administered to healthy postmenopausal women with or without VMS. In Part C, a single dose of ABCL635 or placebo will be administered to postmenopausal women experiencing moderate-to-severe VMS associated with menopause. In Part C, all participants will be offered to participate in an open label extension (OLE) cohort and receive a single dose of ABCL635 upon completion of a 12-week assessment.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Good general health as determined through a review of their medical history and after conducting a general physical examination
- •Body weight ≥ 45 to ≤ 120 kg
- •Body mass index (BMI) between 18.5 kg/m2 and 35.0 kg/m2
- •Non- or ex-smoker (an ex-smoker is defined as someone who completely stopped using nicotine products for at least 90 days prior to the first study drug administration)
- •Healthy man or a postmenopausal woman who is ≥ 40 and ≤ 75 years of age OR a postmenopausal woman with or without VMS and who is ≥ 40 and ≤ 75 years of age OR a postmenopausal woman who is ≥ 40 and ≤ 75 years of age seeking treatment for relief for VMS
- •If a woman:
- •has been compliant with local and/or national guidelines for breast cancer screening with documentation of a mammogram with normal/negative or no clinically significant findings. A screening mammogram may be conducted during study screening period, if needed
- •has spontaneous amenorrhea for at least 12 consecutive months; or spontaneous amenorrhea for at least 6 months with biochemical criteria of menopause (follicle-stimulating hormone [FSH] > 40 IU/L); or had a bilateral oophorectomy > 6 weeks prior to screening, or s/p hysterectomy at least 6 weeks prior to screening and meeting the biochemical criteria of menopause (FSH > 40 IU/L)
- •If a man:
- •possess a testosterone concentration of ≥ 15 nmol/L at the time of screening
- •can procreate and agree to use one of the acceptable contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last drug administration OR is unable to procreate; defined as surgically sterile
排除标准
- •Pregnancy and/or lactation.
- •Has endometrial hyperplasia or history of abnormal uterine bleeding without an identified cause in the past 6 months
- •Previous or current history of a malignant tumor, except for non-melanoma skin cancer.
- •Seated pulse rate less than 50 beats per minute (bpm) or more than 100 bpm or a seated blood pressure < 90/50 mmHg or > 140/90 mmHg
- •eGFR < 60 mL/min/1.73 m2
- •Severe hypersensitivity reactions (like angioedema) to any drugs.
- •Significant uncontrolled cardiovascular, pulmonary, gastrointestinal, hepatic, renal, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease.
- •Clinically significant ECG abnormalities
- •Presence or history of cardiogenic syncope in the past 6 months.
- •Use of any over-the-counter products (including supplements) containing testosterone or any medication (hormonal, prescription, over the counter, herbal, or natural) for the treatment of hot flashes during the screening period and throughout the study; must be discontinued at least 28 days prior to study drug administration
- •Employees of the sponsor or the investigator site and other individuals who are directly involved in the conduct of the study
研究组 & 干预措施
ABCL635 Part A
Part A: healthy male and female participants will receive a single dose of ABCL635 administered by subcutaneous (SC) injection
干预措施: ABCL635 (Biological)
ABCL635 Part C
Part C: postmenopausal women with moderate to severe VMS will receive a single dose of ABCL635 administered by SC injection
干预措施: ABCL635 (Biological)
ABCL635 Part C OLE
Part C open label extension (OLE): postmenopausal women with moderate to severe VMS who received placebo will receive a single dose of ABCL635 administered by SC injection upon completion of 12-week assessment.
干预措施: ABCL635 (Biological)
Placebo Part A
Part A: Healthy male and female participants will receive a single dose of placebo (dextrose 5% solution) administered by SC injection
干预措施: Placebo (Biological)
Placebo Part B
Part B: healthy postmenopausal women with or without VMS will receive up to 3 doses of placebo (dextrose 5% solution) administered by SC injection
干预措施: Placebo (Biological)
ABCL635 Part B
Part B: healthy postmenopausal women with or without VMS will receive up to 3 doses of ABCL635 administered by SC injection
干预措施: ABCL635 (Biological)
Placebo Part C
Part C: postmenopausal women with moderate to severe VMS will receive a single dose of placebo (dextrose 5% solution) administered by SC injection
干预措施: Placebo (Biological)
结局指标
主要结局
Frequency and severity of adverse events (AE)
时间窗: Day 0 to day 197
Number of participants with abnormalities in laboratory parameters, including general biochemistry, hematology, endocrinology, and urinalysis
时间窗: Day 0 to day 197
Number of participants with abnormalities in 12-lead safety electrocardiograms (ECG)
时间窗: Day 0 to day 197
Number of participants with abnormalities in physical examination
时间窗: Day 0 to day 197
次要结局
- Incidence of anti-ABCL635 antibodies(Day 0 to day 197)
- PK parameters; maximum plasma concentration (Cmax)(Day 0 to day 197)
- PK parameters; time to maximum plasma concentration (Tmax)(Day 0 to day 197)
- PK parameters; area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUC0-T)(Day 0 to day 197)
- PK parameters; terminal rate constant (λz)(Day 0 to day 197)
- PK parameters; apparent plasma clearance of drug after extravascular administration (CL/F)(Day 0 to day 197)
- PK parameters; apparent volume of distribution after extravascular administration (Vz/F)(Day 0 to day 197)
- Plasma concentrations of ABCL635(Day 0 to day 197)
- PK parameters; area under the plasma concentration-time curve from zero to hour 672 (AUC0-672)(Day 0 to day 197)
- PK parameters; area under the plasma concentration-time curve from zero to infinity (AUC0-∞)(Day 0 to day 197)
- PK parameters; percent of AUC obtained by extrapolation (%AUCextrap)(Day 0 to day 197)
- PK parameters; half-life (Thalf)(Day 0 to day 197)