A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALV-100 in Participants With Overweight or Obesity With or Without Type 2 Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 180
- 试验地点
- 2
- 主要终点
- Safety and tolerability
研究概览
简要总结
A Study of ALV-100 to Assess Safety, Tolerability, and PK/PD in Overweight/Obese Participants with or without Type 2 Diabetes
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sponsor
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For Part A and B
- •Adult male and female participants, aged 18 to 65 years, inclusive, at the time of signing the informed consent form
- •Body mass index between 27.0 to 39.9 kg/m2 at Screening, both inclusive; overweight should be due to excess adipose tissue, as judged by the Investigator.
- •Have a stable body weight (< 5.0 kg/11 lbs self-reported change) within 90 days prior to Screening
- •Females must be surgically sterile (by means of bilateral salpingectomy, hysterectomy or bilateral oophorectomy) or be post-menopausal (defined as spontaneous cessation of menses for at least 1 year prior to Screening). Females who are post-menopausal and < 55 years must have a follicle-stimulating hormone level > 40 IU/L at Screening.
- •Males with female partners of child-bearing potential must be willing to practice abstinence or must agree to use condom as contraception throughout the duration of the study. This criterion may be waived for male participants who have had a documented successful vasectomy > 6 months before signing the ICF.
- •For Part B only
- •Diagnosis of Type 2 Diabetes for at least 180 days prior to Screening.
- •Glycemic control managed by diet and exercise alone or by stable treatment with metformin and/or sodium-glucose cotransporter 2 inhibitors (SGLT-2i), with no dose changes within 3 months prior to Screening.
- •Hemoglobin A1c (HbA1c) between 6.5 % and 9.0% (equivalent to 48-75 mmol/mol), both inclusive, at Screening.
排除标准
- •For Part A and B
- •History or presence of any clinically relevant respiratory, metabolic (including dyslipidemia, however screening total cholesterol below or equal to 302 mg/dL (7.8 mmol/L) and/or screening triglyceride below or equal to 500 mg/dL (5.65 mmol/L) is accepted), renal, hepatic, gastrointestinal, endocrinological conditions (except conditions associated with type 2 diabetes in Part B) at the discretion of the Investigator.
- •Participants with a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 or a personal history of nonfamilial medullary thyroid carcinoma.
- •Current or history of chronic or acute pancreatitis.
- •Obesity caused by known endocrinologic disorders (e.g., Cushing syndrome) or monogenetic or syndromic forms of obesity (for example, Melanocortin 4 Receptor deficiency or Prader Willi Syndrome).
- •History of major depressive disorder or other severe psychiatric disorder (for example, schizophrenia, bipolar disorder, or anxiety disorder).
- •Lifetime history of a suicide attempt or of any suicidal behavior by endorsement of (answered yes to) any of the items in the suicidal behavior section on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening.
- •Systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg at Screening.
- •History of or current cardiovascular disease, including but not limited to stable and unstable angina, myocardial infarction, congestive heart failure, transient ischemic attack, stroke, clinically significant arrhythmias and conduction disorders or venous thromboembolism.
- •Part A only
- •History or clinical evidence of Type 1 or Type 2 diabetes mellitus, including HbA1c ≥ 6.5% and/or a fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) at Screening (female participants with a history of gestational diabetes are allowed).
- •Part B only
- •Fasting plasma glucose (FPG) > 270 mg/dL (15.0 mmol/L) at Screening.
- •Proliferative retinopathy or maculopathy as judged by the investigator based on a recent (within1.5 years from Screening) ophthalmologic examination.
- •Severe neuropathy as judged by the investigator.
- •Advanced nephropathy (defined as albuminuria ≥ 300 mg/g).
- •History of severe hypoglycemia or hypoglycemic unawareness as judged by the investigator.
研究组 & 干预措施
Part A - Cohort 1 (ALV-100)
Participants with overweight or obesity without type 2 diabetes will receive ascending doses of ALV-100 by subcutaneous injection.
干预措施: ALV-100 (Drug)
Part A - Cohort 1 (Placebo)
Participants with overweight or obesity without type 2 diabetes will receive placebo by subcutaneous injection.
干预措施: Placebo (Drug)
Part B - T2D Cohort (ALV-100)
Participants with overweight or obesity with type 2 diabetes will receive ascending doses of ALV-100 by subcutaneous injection.
干预措施: ALV-100 (Drug)
Part A - Cohort 2 (ALV-100)
Participants with overweight or obesity without type 2 diabetes will receive ascending doses of ALV-100 by subcutaneous injection.
干预措施: ALV-100 (Drug)
Part A - Cohort 4 (ALV-100)
Participants with overweight or obesity without type 2 diabetes will receive ascending doses of ALV-100 by subcutaneous injection.
干预措施: ALV-100 (Drug)
Part A - Cohort 2 (Placebo)
Participants with overweight or obesity without type 2 diabetes will receive placebo by subcutaneous injection.
干预措施: Placebo (Drug)
Part A - Cohort 3 (ALV-100)
Participants with overweight or obesity without type 2 diabetes will receive ascending doses of ALV-100 by subcutaneous injection.
干预措施: ALV-100 (Drug)
Part A - Cohort 3 (Placebo)
Participants with overweight or obesity without type 2 diabetes will receive placebo by subcutaneous injection.
干预措施: Placebo (Drug)
Part A - Cohort 4 (Placebo)
Participants with overweight or obesity without type 2 diabetes will receive placebo by subcutaneous injection.
干预措施: Placebo (Drug)
Part B - T2D Cohort (Placebo)
Participants with overweight or obesity with type 2 diabetes will receive placebo by subcutaneous injection.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and tolerability
时间窗: From First Dose to Week 52
Incidence of treatment emergent adverse events (TEAEs)
次要结局
- Pharmacokinetics (PK) of intact ALV-100 and total ALV-100 - AUC(0-τ), MD(From First Dose to Week 52)
- Pharmacokinetics (PK) of intact ALV-100 and total ALV-100 - Cmax, MD(From First Dose to Week 52)
- Pharmacodynamic (PD) impact on body weight(Baseline, Week 32 and Week 52)
- Pharmacodynamic (PD) impact on body weight percentage(Baseline, Week 32 and Week 52)
- Immunogenicity(From Baseline to Week 52)
- Relationship between ALV-100 serum concentration and QTc interval changes (Part A Only)(From First Dose to Week 52)
- Paracetamol (acetaminophen) absorption test (PAT) (Part A Only)(From First Dose to Week 52)
- Pharmacodynamic (PD) impact of ALV-100 on antidiabetic medication (Part B Only)(From Baseline to Week 32)
- Pharmacodynamic (PD) impact of ALV-100 on glycemic parameters (Part B Only)(Week 32 and Week 52)
- Hypoglycemic Safety (Part B Only)(From Baseline to Week 52)