Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 157 in Subjects With Mild Atopic Asthma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Amgen
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Time-Adjusted Area Under the Curve for the Percent Decrease From Pre-Allergen Challenge in Forced Expiratory Volume in 1 Second (FEV1) From 3 to 7 Hours Post Allergen Challenge
Study Overview
Brief Summary
The purpose of this study is to assess the late and early asthmatic response after an allergen inhalation challenge in adults with mild atopic asthma after receiving multiple doses of tezepelumab (AMG 157), as well as the safety, tolerability, immunogenicity, and pharmacokinetics of multiple doses of tezepelumab in adults with mild atopic asthma.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female subjects with history of mild atopic asthma between 18 and 60 years-of-age
- •Body mass index (BMI) between 18 and 35 kg/m^2
- •Normal or clinically acceptable physical examination (PE), clinical laboratory values, and electrocardiogram (ECG); clinically acceptable PE includes history of mild atopic asthma
- •Used only inhaled short-acting β2-agonists infrequently to treat asthma
- •No current exposure to allergens to which subject experiences asthmatic responses
- •No other lung disease, exacerbations of asthma or lower respiratory tract infections for at least 6 weeks prior to screening
- •Positive skin prick test to common aeroallergens at screening
- •Additional inclusion criteria apply
Exclusion Criteria
- •History or evidence of a clinically significant disorder (including psychiatric), condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion;
- •History or current medical conditions that are contraindicated for methacholine challenge, such as myocardial infarction or stroke within previous 3 months, known cardiac disease, uncontrolled hypertension and aortic or cerebral aneurysm
- •Evidence of active or suspected bacterial, viral, fungal or parasitic infections within past 6 weeks
- •Subject has know type I/II diabetes
- •History of residential exposure to tuberculosis or has a positive purified protein derivative (PPD) or QuantiFERON test within 4 weeks before randomization
- •Subject who has history of malignancy of any type within 5 years prior to enrollment
- •Subjects tested positive for drugs/alcohol or nicotine use at screening
- •Subjects tested positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C
- •Additional exclusion criteria apply
Arms & Interventions
Placebo
Participants received placebo to tezepelumab administered by intravenous infusion on study days 1, 29, and 57.
Intervention: Placebo (Drug)
Tezepelumab 700 mg
Participants received 700 mg tezepelumab administered by intravenous infusion on study days 1, 29, and 57.
Intervention: Tezepelumab (Biological)
Outcomes
Primary Outcomes
Time-Adjusted Area Under the Curve for the Percent Decrease From Pre-Allergen Challenge in Forced Expiratory Volume in 1 Second (FEV1) From 3 to 7 Hours Post Allergen Challenge
Time Frame: Days 42 and 84 at pre-challenge and at 180, 240, 300, 360, and 420 minutes (3-7 hours) post challenge
Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 3 to 7 hours post challenge to assess late asthmatic response (LAR). The percent change in FEV1 from pre-challenge was calculated to each time point between 3 to 7 hours post challenge. The area under the curve for the percent change at each time point was calculated using the linear trapezoidal rule, then time adjusted by dividing by the length of time over which the AUC was calculated.
Maximum Percentage Decrease in Forced Expiratory Volume in 1 Second (FEV1) at 3 to 7 Hours Post Allergen Challenge
Time Frame: Days 42 and 84 at pre-allergen challenge and at 180, 240, 300, 360, and 420 minutes (3-7 hours) post allergen challenge
Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction (measured by a fall in FEV1). FEV1 was measured prior to the challenge and between 3 to 7 hours post allergen challenge to assess late asthmatic response (LAR). The percent change in FEV1 from pre-challenge was calculated to each time point between 3 to 7 hours post challenge. The maximum percent decrease in FEV1 from pre-allergen challenge is the percent change in FEV1 representing the largest percentage decrease (or minimum percentage increase) from pre-allergen challenge FEV1 during late (3-7 hour) asthmatic response time frame.
Secondary Outcomes
- Number of Participants With Grade ≥ 3 Laboratory Values(Up to 169 days)
- Number of Participants Who Developed Anti-tezepelumab Antibodies After Initiation of Treatment(Days 29, 57, 85, 113, and 169)
- Maximum Percentage Decrease in FEV1 From 0 to 2 Hours Post Allergen Challenge(Days 42 and 84 at pre-allergen challenge and at 10, 20, 30, 45, 60, 90, and 120 minutes (0-2 hours) post allergen challenge)
- Time-Adjusted AUC for the Percent Decrease From Pre-Allergen Challenge in FEV1 From 0 to 2 Hours Post Allergen Challenge(Days 42 and 84 at pre-challenge and at 10, 20, 30, 45, 60, 90, and 120 minutes (0-2 hours) post challenge)
- Number of Participants With Adverse Events(Up to 169 days)
- Minimum FEV1 From 0 to 2 Hours Post Allergen Challenge(Days 42 and 84 at 10, 20, 30, 45, 60, 90, and 120 minutes (0-2 hours) post allergen challenge)
- Time-Adjusted AUC for FEV1 From 0 to 2 Hours Post Allergen Challenge(Days 42 and 84 at pre-challenge and at 10, 20, 30, 45, 60, 90, and 120 minutes (0-2 hours) post challenge)
- Minimum FEV1 From 3 to 7 Hours Post Allergen Challenge(Days 42 and 84 at 180, 240, 300, 360, and 420 minutes (3-7 hours) post allergen challenge)
- Time-Adjusted AUC for FEV1 From 3 to 7 Hours Post Allergen Challenge(Days 42 and 84 at pre-challenge and at 180, 240, 300, 360, and 420 minutes (3-7 hours) post challenge.)
- Maximum Observed Serum Concentration (Cmax) of Tezepelumab(First dose: Day 1 at predose and 1 and 4 hours postdose, and days 4, 8, 15, and 29 (predose); Last dose: Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.)
- Time of Maximum Observed Concentration (Tmax) of Tezepelumab(First dose: Day 1 at predose and 1 and 4 hours postdose, and days 4, 8, 15, and 29 (predose); Last dose: Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.)
- Minimum Observed Serum Concentration (Cmin) of Tezepelumab(First dose: Day 1 at predose and 1 and 4 hours postdose, and days 4, 8, 15, and 29 (predose); Last dose: Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.)
- Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) for Tezepelumab(First dose: Day 1 at predose and 1 and 4 hours postdose and days 4, 8, 15, and 29 (predose); Last dose: Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, and 85.)
- Accumulation Ratio Based on AUCtau(First dose: Day 1 at predose and 1 and 4 hours postdose and days 4, 8, 15, and 29 (predose); Last dose: Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, and 85.)
- Accumulation Ratio Based on Cmax(First dose: Day 1 at predose and 1 and 4 hours postdose, and days 4, 8, 15, and 29 (predose); Last dose: Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.)
- Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) After Last Dose for Tezepelumab(Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.)
- Terminal Half-life (t1/2z) of Tezepelumab After Last Dose(Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.)