NCT06401044进行中（未招募）1 期
A Phase 1/2, Randomized, Double-Masked, Placebo-Controlled, Multicenter Study to Assess the Safety, Pharmacokinetics, and Efficacy of AMG 732 in Healthy Subjects and Subjects With Moderate-to-Severe Active Thyroid Eye Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Amgen
- 入组人数
- 94
- 试验地点
- 44
- 主要终点
- Part A: Number of Participants With Treatment-emergent Adverse Events
研究概览
简要总结
The primary objective of Part A of this study is to investigate the safety and tolerability of AMG 732 after single subcutaneous (SC) doses. The primary objective of Part B of this study is to investigate the efficacy of AMG 732 in participants with Thyroid Eye Disease (TED) after multiple SC doses.
详细描述
Recruitment has ended for the Phase 1 portion of the study and will reopen when Phase 2 begins recruitment.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for Part A/Phase 1 only:
- •Participant has provided informed consent before initiation of any study-specific activities/procedures.
- •Male or female aged 18 to 55 years (Part A).
- •Female participants must be of non-childbearing potential.
- •Body mass index (BMI) between 18 and 30 kg/m^2, inclusive, at screening.
- •The participant has adequate venous access and can receive intravenous (IV) therapy.
- •The participant is considered by the investigator or designee to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead electrocardiogram (ECG) results, and physical examination findings at screening.
- •Healthy Japanese participants in cohort 4 only. Japanese participants must meet all the following as confirmed by interview: Descendants of 4 ethnic Japanese grandparents who were born in Japan; Both parents are ethnic Japanese who were born in Japan; Hold a Japanese passport or identity papers; Have lived outside Japan for less than 10 years at the time of screening and lifestyle including diet has not changed significantly since leaving Japan.
- •Inclusion criteria for Part B/Phase 2 only:
- •Male or female aged 18 to 65 years.
- •Moderate-to-severe active TED.
- •The participant had onset of active TED within 15 months prior to baseline.
- •Clinical diagnosis of Graves' disease associated with active TED with a Clinical Activity Score (CAS)≥3 for the most severely affected eye at screening and baseline.
- •Proptosis ≥18mm in the study eye at baseline.
- •Participants with baseline subjective binocular diplopia score >
- •Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the trial.
排除标准
- •for Part A and Part B:
- •Malignant condition in the past 12 months or major surgery within 8 weeks or plans to have an elective surgery from screening through end of study.
- •Active liver or kidney disfunction at screening.
- •Positive test for hepatitis B/C or Human immunodeficiency virus (HIV) serology at screening.
- •Glycated hemoglobin (HbA1c) > 6.5% and/or fasting glucose levels> 126 mg/dL (> 7 mmol/L) at screening.
- •Use of any steroid (IV, oral, steroid eye drops) within 3 weeks prior to the first dose. Steroids cannot be initiated during the trial. Exceptions include topical and inhaled steroids and steroids used to treat injection related reactions or short course of steroid for asthma control.
- •Known hypersensitivity to teprotumumab or any other monoclonal antibody products.
- •History of substance abuse within 12 months before screening.
- •Donated blood, or had significant blood loss, or received a transfusion of any blood or blood products within 60 days prior to day 1 dosing or received a plasma donation within 7 days prior to day 1 dosing.
- •Exclusion criteria for PartA/Phase 1 only
- •Blood pressure or ECG abnormalities at screening.
- •Exclusion criteria for Part B/Phase 2 only:
- •Use of any steroid or other non-steroid immunosuppressive agent, monoclonal antibody, within 3 months prior to the first injection of study drug.
- •Use of teprotumumab or any other IGF-1R inhibitor.
- •Prior orbital irradiation or decompression in the study eye.
- •History or existing inflammatory bowel disease (ulcerative colitis or Crohn's disease).
- •Other protocol-defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Part B: AMG 732 Medium Dose
Experimental
Participants will receive AMG 732 medium dose SC.
干预措施: AMG 732 (Drug)
Part B: Placebo
Placebo Comparator
Participants will receive placebo SC.
干预措施: Placebo (Other)
Part B: AMG 732 High Dose
Experimental
Participants will receive AMG 732 high dose SC.
干预措施: AMG 732 (Drug)
Part A: Placebo
Placebo Comparator
Participants in 6 cohorts will receive either AMG 732 or placebo in Single Ascending Doses (SAD).
干预措施: Placebo (Other)
Part A: AMG 732
Experimental
Participants in 6 cohorts will receive either AMG 732 or placebo in Single Ascending Doses (SAD).
干预措施: AMG 732 (Drug)
Part B: AMG 732 Low Dose
Experimental
Participants will receive AMG 732 low dose SC.
干预措施: AMG 732 (Drug)
结局指标
主要结局
Part A: Number of Participants With Treatment-emergent Adverse Events
时间窗: Day 1 through Week 36 (End of Study)
Part A: Number of Participants With Treatment-emergent Adverse Events
时间窗: Day 1 through Week 36 (End of Study)
Part B: Change from Baseline in Proptosis Measurement by an Exophthalmometer in the Study Eye
时间窗: Baseline to End of Treatment (EoT) (approximately 6 Months)
次要结局
- Part A: Maximum Observed Plasma Concentration (Cmax) of AMG 732(Up to Week 36)
- Part A: Time to Cmax (Tmax) of AMG 732(Up to Week 36)
- Part A: Area Under the Plasma Concentration-time Curve (AUC) of AMG 732(Up to Week 36)
- Part A: Half-life (t1/2) of AMG 732(Up to Week 36)
- Part A: Number of Participants With Anti-drug Antibodies (ADAs)(Up to Week 36)
- Part B: Number of Participants With Treatment-emergent Adverse Events(Up to Week 48)
- Part B: Cmax of AMG 732(Up to Week 48)
- Part B: Tmax of AMG 732(Up to Week 48)
- Part B: AUC of AMG 732 Over the Dosing Interval(Up to Week 48)
- Part B: Accumulation of AMG 732 Following Multiple Dosing(Up to Week 48)
- Part B: Half-life (t1/2) of AMG 732(Up to Week 48)
- Part B: Number of Participants With Anti-drug Antibodies (ADAs)(Up to Week 48)
- Part B: Mean Change from Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Visual Functioning (VF) Subscale Score(Baseline to EoT (approximately 6 Months))
- Part B: Mean Change from Baseline in the GO-QoL Appearance (A) Subscale Score(Baseline to EoT (approximately 6 Months))
- Part B: Proptosis Response Status in the Study Eye(EoT (approximately 6 Months))
- Part A: Maximum Observed Plasma Concentration (Cmax) of AMG 732(Up to Week 36)
- Part A: Time to Cmax (Tmax) of AMG 732(Up to Week 36)
- Part A: Area Under the Plasma Concentration-time Curve (AUC) of AMG 732(Up to Week 36)
- Part A: Half-life (t1/2) of AMG 732(Up to Week 36)
- Part A: Number of Participants With Anti-drug Antibodies (ADAs)(Up to Week 36)
- Part B: Number of Participants With Treatment-emergent Adverse Events(Up to Week 48)
- Part B: Cmax of AMG 732(Up to Week 48)
- Part B: Tmax of AMG 732(Up to Week 48)
- Part B: AUC of AMG 732 Over the Dosing Interval(Up to Week 48)
- Part B: Accumulation of AMG 732 Following Multiple Dosing(Up to Week 48)
- Part B: Half-life (t1/2) of AMG 732(Up to Week 48)
- Part B: Number of Participants With Anti-drug Antibodies (ADAs)(Up to Week 48)
- Part B: Proptosis Response Status in the Study Eye(EoT (approximately 6 Months))
- Part B: Mean Change from Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Visual Functioning (VF) Subscale Score(Baseline to EoT (approximately 6 Months))
- Part B: Mean Change from Baseline in the GO-QoL Appearance (A) Subscale Score(Baseline to EoT (approximately 6 Months))
研究者
研究点 (44)
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