Clinical trial NCT01405963: Double-blind, Multiple Dose Study of Tezepelumab (AMG 157) in Adults With Mild Atopic Asthma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: Amgen
AMG 157
Asthma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2011-07-29
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Percentage Decrease in Forced Expiratory Volume in 1 Second (FEV1) at 3 to 7 Hours Post Allergen Challenge
timeFrame: Days 42 and 84 at pre-allergen challenge and at 180, 240, 300, 360, and 420 minutes (3-7 hours) post allergen challenge
measure: 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
timeFrame: Days 42 and 84 at pre-challenge and at 180, 240, 300, 360, and 420 minutes (3-7 hours) post challenge
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Up to 169 days
measure: Number of Participants With Grade ≥ 3 Laboratory Values
timeFrame: Up to 169 days
measure: Number of Participants Who Developed Anti-tezepelumab Antibodies After Initiation of Treatment
timeFrame: Days 29, 57, 85, 113, and 169
measure: Maximum Percentage Decrease in FEV1 From 0 to 2 Hours Post Allergen Challenge
timeFrame: 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
measure: Time-Adjusted AUC for the Percent Decrease From Pre-Allergen Challenge in FEV1 From 0 to 2 Hours Post Allergen Challenge
timeFrame: Days 42 and 84 at pre-challenge and at 10, 20, 30, 45, 60, 90, and 120 minutes (0-2 hours) post challenge
measure: Minimum FEV1 From 0 to 2 Hours Post Allergen Challenge
timeFrame: Days 42 and 84 at 10, 20, 30, 45, 60, 90, and 120 minutes (0-2 hours) post allergen challenge
measure: Time-Adjusted AUC for FEV1 From 0 to 2 Hours Post Allergen Challenge
timeFrame: Days 42 and 84 at pre-challenge and at 10, 20, 30, 45, 60, 90, and 120 minutes (0-2 hours) post challenge
measure: Minimum FEV1 From 3 to 7 Hours Post Allergen Challenge
timeFrame: Days 42 and 84 at 180, 240, 300, 360, and 420 minutes (3-7 hours) post allergen challenge
measure: Time-Adjusted AUC for FEV1 From 3 to 7 Hours Post Allergen Challenge
timeFrame: Days 42 and 84 at pre-challenge and at 180, 240, 300, 360, and 420 minutes (3-7 hours) post challenge.
measure: Maximum Observed Serum Concentration (Cmax) of Tezepelumab
timeFrame: 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.
measure: Time of Maximum Observed Concentration (Tmax) of Tezepelumab
timeFrame: 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.
measure: Minimum Observed Serum Concentration (Cmin) of Tezepelumab
timeFrame: 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.
measure: Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) for Tezepelumab
timeFrame: 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.
measure: Accumulation Ratio Based on AUCtau
timeFrame: 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.
measure: Accumulation Ratio Based on Cmax
timeFrame: 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.
measure: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) After Last Dose for Tezepelumab
timeFrame: Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.
measure: Terminal Half-life (t1/2z) of Tezepelumab After Last Dose
timeFrame: Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Sainte-Foy
country: Canada
facility: Research Site
state: Quebec
city: Saskatoon
country: Canada
facility: Research Site
state: Saskatchewan
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Gauvreau GM, O'Byrne PM, Boulet LP, Wang Y, Cockcroft D, Bigler J, FitzGerald JM, Boedigheimer M, Davis BE, Dias C, Gorski KS, Smith L, Bautista E, Comeau MR, Leigh R, Parnes JR. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med. 2014 May 29;370(22):2102-10. doi: 10.1056/NEJMoa1402895. Epub 2014 May 20.