- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01405963
Double-blind, Multiple Dose Study of Tezepelumab (AMG 157) in Adults With Mild Atopic Asthma
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 Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Alberta
-
Calgary, Alberta, Canada, T2N 4Z6
- Research Site
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V5Z 1M9
- Research Site
-
-
Ontario
-
Hamilton, Ontario, Canada, L8N 3Z5
- Research Site
-
-
Quebec
-
Sainte-Foy, Quebec, Canada, G1V 4G5
- Research Site
-
-
Saskatchewan
-
Saskatoon, Saskatchewan, Canada, S7N 0W8
- Research Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Participants received placebo to tezepelumab administered by intravenous infusion on study days 1, 29, and 57.
|
Administered in a 1-hour intravenous infusion
|
Experimental: Tezepelumab 700 mg
Participants received 700 mg tezepelumab administered by intravenous infusion on study days 1, 29, and 57.
|
Administered in a 1-hour intravenous infusion
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
Days 42 and 84 at pre-allergen challenge and at 180, 240, 300, 360, and 420 minutes (3-7 hours) post allergen challenge
|
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. |
Days 42 and 84 at pre-challenge and at 180, 240, 300, 360, and 420 minutes (3-7 hours) post challenge
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events
Time Frame: Up to 169 days
|
A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria:
|
Up to 169 days
|
Number of Participants With Grade ≥ 3 Laboratory Values
Time Frame: Up to 169 days
|
Laboratory toxicities were graded according to the Common Terminology Criteria for Adverse Events (Version 4) on a scale from grade 1 (mild) to 5 (death).
|
Up to 169 days
|
Number of Participants Who Developed Anti-tezepelumab Antibodies After Initiation of Treatment
Time Frame: Days 29, 57, 85, 113, and 169
|
All study samples (tezepelumab and placebo) were tested using an electrochemiluminescence (ECL) based immunoassay to detect and confirm the presence of antibodies capable of binding to tezepelumab. Samples identified as positive in the immunoassay were tested in a receptor-binding ECL-based assay to detect neutralizing or inhibitory effects toward tezepelumab. The number of participants with positive anti-tezepelumab binding antibodies / neutralizing antibodies at any time post-baseline with a negative or no result at baseline is reported. |
Days 29, 57, 85, 113, and 169
|
Maximum Percentage Decrease in FEV1 From 0 to 2 Hours Post Allergen Challenge
Time Frame: 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
|
Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 0 to 2 hours post challenge to assess early asthmatic response (EAR). 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 early (0-2 hour) asthmatic response time frame. |
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
Time Frame: Days 42 and 84 at pre-challenge and at 10, 20, 30, 45, 60, 90, and 120 minutes (0-2 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 0 to 2 hours post challenge to assess early asthmatic response (EAR). The percent change in FEV1 from pre-allergen challenge was calculated to each time point between 0 to 2 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. |
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 0 to 2 Hours Post Allergen Challenge
Time Frame: Days 42 and 84 at 10, 20, 30, 45, 60, 90, and 120 minutes (0-2 hours) post allergen 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 0 to 2 hours post challenge to assess early asthmatic response (EAR). The minimum FEV1 post onset of the allergen challenge for EAR is defined as the smallest value of FEV1 measured during 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
Time Frame: Days 42 and 84 at pre-challenge and at 10, 20, 30, 45, 60, 90, and 120 minutes (0-2 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 0 to 2 hours post challenge to assess early asthmatic response (EAR). The area under the curve for the FEV1 between 0 to 2 hours post allergen challenge was calculated using the linear trapezoidal rule, then time adjusted by dividing by the length of time over which the AUC was calculated. |
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
Time Frame: Days 42 and 84 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. FEV1 was measured prior to the challenge and between 3 to 7 hours post challenge to assess late asthmatic response (LAR). The minimum FEV1 post allergen challenge for LAR is defined as the smallest value of FEV1 measured during 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
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 allergen challenge to assess late asthmatic response (LAR). The area under the curve for the FEV1 between 3 to 7 hours post allergen challenge was calculated using the linear trapezoidal rule, then time adjusted by dividing by the length of time over which the AUC was calculated. |
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
Time Frame: 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.
|
The PK parameter Cmax was estimated based on the serum concentrations of tezepelumab using noncompartmental methods.
The concentration of tezepelumab in human serum was measured using a validated ELISA.
The lower limit of quantification of the assay was 10 ng/mL.
|
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
Time Frame: 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.
|
The PK parameter Tmax was estimated based on the serum concentrations of tezepelumab using noncompartmental methods.
The concentration of tezepelumab in human serum was measured using a validated ELISA.
The lower limit of quantification of the assay was 10 ng/mL.
|
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
Time Frame: 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.
|
The PK parameter Cmin was estimated based on the serum concentrations of tezepelumab using noncompartmental methods.
The concentration of tezepelumab in human serum was measured using a validated ELISA.
The lower limit of quantification of the assay was 10 ng/mL.
|
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
Time Frame: 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.
|
The PK parameter AUCtau was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The dosing interval (tau) was 28 days. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL. |
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
Time Frame: 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 (AR) based on AUCtau was calculated as AUCtau after last dose / AUCtau after first dose.
|
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
Time Frame: 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.
|
Accumulation ratio based on Cmax calculated as Cmax after last dose / Cmax after first dose.
|
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
Time Frame: Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.
|
The PK parameter AUCinf was estimated based on the serum concentrations of tezepelumab using noncompartmental methods.
The concentration of tezepelumab in human serum was measured using a validated ELISA.
The lower limit of quantification of the assay was 10 ng/mL.
|
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
Time Frame: Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.
|
The PK parameter t1/2,z was estimated based on the serum concentrations of tezepelumab using noncompartmental methods.
The concentration of tezepelumab in human serum was measured using a validated ELISA.
The lower limit of quantification of the assay was 10 ng/mL.
|
Day 57 predose, 1 and 4 hours postdose, and at days 60, 64, 71, 83, 84, 85, 113, and 169.
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20101183
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Asthma
-
Vanderbilt University Medical CenterNot yet recruitingAsthma in Children | Asthma Attack | Asthma Acute | Acute Asthma Exacerbation | Asthma; StatusUnited States
-
University of California, San FranciscoCompletedAsthma in Children | Asthma Attack | Asthma Acute | Asthma ChronicUnited States
-
SingHealth PolyclinicsNot yet recruitingAsthma | Asthma in Children | Asthma Attack | Asthma Acute | Asthma Chronic
-
Johann Wolfgang Goethe University HospitalCompleted
-
Universita di VeronaCompleted
-
Parc de Salut MarActive, not recruitingAsthma in Children | Persistent Asthma | Asthma ExacerbationSpain
-
Forest LaboratoriesCompleted
-
Brunel UniversityKarolinska InstitutetUnknown
-
Value Outcomes Ltd.AstraZenecaCompletedAsthma, Bronchial | Bronchial Asthma | Asthma Chronic | Asthma; EosinophilicCzechia
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States