Clinical trial NCT01402986: A Safety and Efficacy Study of Tralokinumab in Adults With Asthma
Official title: A Phase 2b, Randomized, Double-blind Study to Evaluate the Efficacy of Tralokinumab in Adults With Uncontrolled, Severe Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Tralokinumab
CAT-354
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2011-07-27
Enrollment: 689
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the addition of tralokinumab to standard asthma medication is effective in the treatment of adults with asthma.

Detailed description: Interleukin-13 (IL-13) is a key mediator in the pathogenesis of established asthmatic disease. Tralokinumab is a human monoclonal antibody that blocks IL-13, which may result in improved control of asthma. This study will determine whether the addition of tralokinumab to standard asthma medications results in a reduced rate of asthma exacerbations in subjects with severe asthma.

Eligibility criteria: Inclusion Criteria:

* Age 18-75 years
* Body mass index (BMI) between 16-40 kilogram per square meter (kg/m\^2) at Visit 1
* Uncontrolled severe asthma
* A chest x-ray with no abnormality
* Females of childbearing potential who are sexually active with a non-sterilized male partner must use highly effective contraception from Day 1
* Non-sterilized males or sterilized males who are less than or equal to (=\<) 1 year post-vasectomy who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception

Exclusion Criteria:

* Employee of the clinical study site or any other individuals directly involved with the conduct of the study, or immediate family members of such individuals
* Pregnant or breastfeeding women
* Any other respiratory disease
* Previously taken tralokinumab (the study drug)
* Current smoker or a history of smoking which would be more than 1 pack per day for 10 years
* Known immune deficiency
* History of cancer
* Hepatitis B, C or Human Immuno-deficiency Virus (HIV)
* Any disease which may cause complications whilst taking the study drug.

Primary outcomes:
measure: Annual Asthma Exacerbation Rate (AER)
timeFrame: Week 1 up to Week 53
Secondary outcomes:
measure: Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53
timeFrame: Baseline and Week 53
measure: Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53
timeFrame: Baseline and Week 53
measure: Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53
timeFrame: Baseline and Week 53
measure: Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53
timeFrame: Baseline and Week 53
measure: Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53
timeFrame: Baseline and Week 53
measure: Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home
timeFrame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
measure: Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home
timeFrame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
measure: Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53
timeFrame: Baseline and Week 53
measure: Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53
timeFrame: Baseline and Week 53
measure: Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53
timeFrame: Week 53
measure: Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Week 53
timeFrame: Baseline and Week 53
measure: Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53
timeFrame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
measure: Change From Baseline in Rescue Medication Use at Week 53
timeFrame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs)
timeFrame: Baseline and Week 75
measure: Observed Serum Tralokinumab Concentration at Week 53
timeFrame: Week 53
measure: Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab
timeFrame: Baseline and Week 75
measure: Severe Annual Asthma Exacerbation Rate (AER)
timeFrame: Week 1 up to Week 53
measure: Time to First Exacerbation Through Week 53
timeFrame: Week 1 up to Week 53
measure: Time to First Severe Exacerbation Through Week 53
timeFrame: Week 1 up to Week 53
measure: Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin
timeFrame: Week 1 up to Week 53
measure: Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status
timeFrame: Week 1 up to Week 53
measure: Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count
timeFrame: Week 1 up to Week 53
measure: Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility
timeFrame: Week 1 up to Week 53
measure: Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted
timeFrame: Week 1 up to Week 53
measure: Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year
timeFrame: Week 1 up to Week 53
measure: Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin
timeFrame: Week 1 up to Week 53
measure: Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility
timeFrame: Week 1 up to Week 53
measure: Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status
timeFrame: Week 1 up to Week 53
measure: Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count
timeFrame: Week 1 up to Week 53
measure: Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups
timeFrame: Week 1 up to Week 53
measure: Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups
timeFrame: Week 1 up to Week 53
measure: Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups
timeFrame: Week 1 up to Week 53
measure: Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status
timeFrame: Week 1 up to Week 53
measure: Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use
timeFrame: Week 1 up to Week 53
measure: Change From Baseline in Percentage of Nighttime Awakening at Week 53
timeFrame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
measure: Change From Baseline in Overall Activity Limitations at Week 53
timeFrame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
measure: Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53
timeFrame: Baseline and Week 53
measure: Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53
timeFrame: Baseline and Week 53
measure: Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53
timeFrame: Baseline and Week 53
measure: Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53
timeFrame: Baseline and Week 53
measure: Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home
timeFrame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
measure: Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home
timeFrame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
Other outcomes:
Locations:
city: Rancho Mirage
country: United States
facility: Research Site
state: California
city: Centennial
country: United States
facility: Research Site
state: Colorado
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Cocoa
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
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state: Florida
city: Winter Park
country: United States
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state: Florida
city: Albany
country: United States
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state: Georgia
city: Fargo
country: United States
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state: North Dakota
city: Philadelphia
country: United States
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state: Pennsylvania
city: Upland
country: United States
facility: Research Site
state: Pennsylvania
city: Killeen
country: United States
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state: Texas
city: Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aires
country: Argentina
facility: Research Site
city: Monte Grande
country: Argentina
facility: Research Site
city: Ranelagh
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
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state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Quillota
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Valparaiso
country: Chile
facility: Research Site
city: Viña del Mar
country: Chile
facility: Research Site
city: Jindrichuv Hradec
country: Czech Republic
facility: Research Site
city: Plzen
country: Czech Republic
facility: Research Site
city: Rokycany
country: Czech Republic
facility: Research Site
city: Marseille Cedex 20
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Paris Cedex 18
country: France
facility: Research Site
city: Perpignan
country: France
facility: Research Site
city: Pessac
country: France
facility: Research Site
city: Strasbourg Cedex
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fujisawa-shi
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Habikino-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Itabashi-ku
country: Japan
facility: Research Site
city: Kagoshima-shi
country: Japan
facility: Research Site
city: Kahoku-gun
country: Japan
facility: Research Site
city: Kishiwada-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Maebashi-shi
country: Japan
facility: Research Site
city: Morioka-shi
country: Japan
facility: Research Site
city: Naka-gun
country: Japan
facility: Research Site
city: Sagamihara-shi
country: Japan
facility: Research Site
city: Sakaide-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sumida-ku
country: Japan
facility: Research Site
city: Takatsuki-shi
country: Japan
facility: Research Site
city: Tomakomai-shi
country: Japan
facility: Research Site
city: Wakayama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Bucheon-si
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Culiacan
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Morelia
country: Mexico
facility: Research Site
city: México
country: Mexico
facility: Research Site
city: Santiago de Querétaro
country: Mexico
facility: Research Site
city: Tampico
country: Mexico
facility: Research Site
city: Villahermosa
country: Mexico
facility: Research Site
city: Iloilo City
country: Philippines
facility: Research Site
city: Lipa City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Zabrze
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Vladikavkaz
country: Russian Federation
facility: Research Site
city: Yekaterinburg
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Sagunto(Valencia)
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Sponsor GmbH
name: Edward Piper, MBBS
role: STUDY_DIRECTOR
affiliation: Institute for Lung Health
name: Christopher Brightling
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brightling CE, Chanez P, Leigh R, O'Byrne PM, Korn S, She D, May RD, Streicher K, Ranade K, Piper E. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015 Sep;3(9):692-701. doi: 10.1016/S2213-2600(15)00197-6. Epub 2015 Jul 28.
citation: Baverel PG, White N, Vicini P, Karlsson MO, Agoram B. Dose-Exposure-Response Relationship of the Investigational Anti-Interleukin-13 Monoclonal Antibody Tralokinumab in Patients With Severe, Uncontrolled Asthma. Clin Pharmacol Ther. 2018 May;103(5):826-835. doi: 10.1002/cpt.803. Epub 2017 Sep 28.