NCT06401044
Recruiting
Phase 1
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
Overview
- Phase
- Phase 1
- Intervention
- AMG 732
- Conditions
- Thyroid Eye Disease
- Sponsor
- Amgen
- Enrollment
- 88
- Locations
- 30
- Primary Endpoint
- Part A: Number of Participants With Treatment-emergent Adverse Events
- Status
- Recruiting
- Last Updated
- 23 days ago
Overview
Brief Summary
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.
Detailed Description
Recruitment has ended for the Phase 1 portion of the study and will reopen when Phase 2 begins recruitment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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
Arms & Interventions
Part B: AMG 732 Medium Dose
Participants will receive AMG 732 medium dose SC.
Intervention: AMG 732
Part B: AMG 732 High Dose
Participants will receive AMG 732 high dose SC.
Intervention: AMG 732
Part B: Placebo
Participants will receive placebo SC.
Intervention: Placebo
Part A: Placebo
Participants in 6 cohorts will receive either AMG 732 or placebo in Single Ascending Doses (SAD).
Intervention: Placebo
Part B: AMG 732 Low Dose
Participants will receive AMG 732 low dose SC.
Intervention: AMG 732
Part A: AMG 732
Participants in 6 cohorts will receive either AMG 732 or placebo in Single Ascending Doses (SAD).
Intervention: AMG 732
Outcomes
Primary Outcomes
Part A: Number of Participants With Treatment-emergent Adverse Events
Time Frame: Day 1 through Week 36 (End of Study)
Part A: Number of Participants With Treatment-emergent Adverse Events
Time Frame: Day 1 through Week 36 (End of Study)
Part B: Change from Baseline in Proptosis Measurement by an Exophthalmometer in the Study Eye
Time Frame: Baseline to End of Treatment (EoT) (approximately 6 Months)
Secondary Outcomes
- 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: Time to Cmax (Tmax) of AMG 732(Up to Week 36)
- Part A: Maximum Observed Plasma Concentration (Cmax) 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))
Study Sites (30)
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