A Phase 1, Randomized, Double-blind, Placebo-controlled, Integrated Single Ascending Dose, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 691 in Healthy Participants and Participants With Mild-to-Moderate Asthma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Amgen
- 入组人数
- 21
- 试验地点
- 36
- 主要终点
- Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The main objective of this study is to assess the safety and tolerability of AMG 691 as single doses (healthy participants only) and multiple doses in healthy participants and participants with mild-to-moderate asthma.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion Part A and B
- •Participants must be capable of giving informed consent and have provided informed consent.
- •Participants must be 18 to 65, inclusive at time of signing of informed consent.
- •Participants must have a Body Mass Index between 18.0 to 30 kg/m^2 and total body weight ≥ 40 kg at screening.
- •Participants must be overtly healthy as determined by the investigator based on medical evaluation and study screening procedures.
- •Female participants must be of non-childbearing potential.
- •Inclusion Part C
- •Participants must be capable of giving informed consent and have provided informed consent.
- •Participants must be 18 to 70, inclusive at time of signing of informed consent.
- •Body mass index between 18.0 to 35 kg/m^2 and total body weight ≥ 40 kg at screening.
- •Participants must have documentation of physician diagnosed asthma for ≥ 12 months prior to screening.
- •Participants must have documented bronchodilator responsiveness of forced expiratory volume in 1 second (FEV1) ≥ 10% in the 10 years before screening or at the screening visit.
- •Participants must have a pre-bronchodilator percent predicted FEV1 ≥ 50% at screening visit and Day -
- •For participants on high-dose ICS, participants must have a percent-predicted FEV1 ≥ 70% at screening visit and on day -
- •Participants must have peripheral blood eosinophils ≥ 200 cells/μl at screening visit and Day -
- •Participants must have a fractional exhaled nitric oxide (FeNO) ≥ 25 ppb at screening visit and Day -
- •Participant must not use inhaled corticosteroids (ICS) or must be treated with low-dose, medium-dose, or high-dose ICS and on a stable dose for a minimum of 12 weeks prior to screening.
- •Exclusion (applicable to all study parts)
- •History of malignancy (except for in situ cervical cancer or surgically excised non-melanoma skin cancer occurring more than 5 years prior to randomization).
- •History of anaphylaxis or hypersensitivity to biologic therapy or sensitivity to mammalian derived products.
- •History of immunodeficiency or history of severe infection within the last 3 years requiring IV antibiotics.
- •History of tuberculosis (TB), TB symptoms, or positive interferon gamma release assay.
- •History of untreated or unresolved helminthic infection within 24 weeks of day
- •Positive human immunodeficiency virus (HIV) antibodies, hepatitis B core antigen, hepatitis B core antibody, or hepatitis C virus (HCV) ribonucleic acid (RNA).
- •Male participants unwilling to follow contraceptive requirements.
- •Additional Exclusion for Part C only
- •Female of childbearing potential not willing to use 2 methods of contraception with one being a highly effective method of contraception.
- •History of pulmonary disease that may interfere with interpretation of study results.
- •History of upper respiratory infection within 6 weeks of screening.
- •Asthma Control Questionnaire (ACQ-6) >
- •Asthma symptoms or exacerbations requiring 2 or more systemic corticosteroid bursts (≥10 mg/day prednisone or equivalent for ≥ 3 days each) in the previous 12 months.
- •More than one hospitalization or emergency department visit in the last year.
- •History of life-threatening asthma exacerbation after the 12 years age requiring admission to intensive care unit.
排除标准
- 未提供
研究组 & 干预措施
Part C: Multiple Dose
Participants with mild-to-moderate asthma will be randomized in a 2:1 ratio to receive either AMG 691 or placebo.
干预措施: AMG 691 (Drug)
Part A: Single Ascending Dose (SAD)
Healthy participants will be randomized in a 3:1 ratio to receive either AMG 691 or placebo.
干预措施: Placebo (Drug)
Part B: Multiple Ascending Dose (MAD)
Healthy participants will be randomized in a 3:1 ratio to receive either AMG 691 or placebo.
干预措施: Placebo (Drug)
Part C: Multiple Dose
Participants with mild-to-moderate asthma will be randomized in a 2:1 ratio to receive either AMG 691 or placebo.
干预措施: Placebo (Drug)
Part A: Single Ascending Dose (SAD)
Healthy participants will be randomized in a 3:1 ratio to receive either AMG 691 or placebo.
干预措施: AMG 691 (Drug)
Part B: Multiple Ascending Dose (MAD)
Healthy participants will be randomized in a 3:1 ratio to receive either AMG 691 or placebo.
干预措施: AMG 691 (Drug)
结局指标
主要结局
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to approximately 11 months
An adverse event (AE) is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurred after the participant received study treatment. Serious AEs (SAEs) are defined as any untoward medical occurrence that, meet at least 1 of the following serious criteria: Immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect. Includes AEs of interest (AEOI), and AEs leading to discontinuation.
次要结局
- Maximum Concentration (Cmax) of AMG 691(Up to approximately 11 months)
- Area Under the Curve (AUC) of AMG 691(Up to approximately 11 months)