Clinical trial NCT02194699: A Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults and Adolescents With Uncontrolled Asthma
Official title: A Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults and Adolescents With Asthma Inadequately Controlled on Inhaled Corticosteroid Plus Long-Acting β2-Agonist
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uncontrolled Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-07-18
Enrollment: 856
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A 52-Week, Multicentre, Randomized, Double-Blind, Parallel Group, Placebo Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults and Adolescents with Asthma Inadequately Controlled on Inhaled Corticosteroid Plus Long-Acting β2-Agonist

Detailed description: This is a randomized, double-blind, parallel group, placebo-controlled study designed to evaluate efficacy and safety of tralokinumab administered subcutaneously in subjects with uncontrolled asthma on inhaled corticosteroid plus long-acting β2-agonist and having a history of asthma exacerbations. Approximately 770 subjects will be randomized globally. Subjects will receive tralokinumab, or placebo, administered via subcutaneous injection at the study site, over a 52-week treatment period.

Eligibility criteria: Inclusion Criteria:

1. Age 12 -75
2. Documented physician-diagnosed asthma.
3. Documented treatment with ICS at a total daily dose corresponding to ≥500μg fluticasone propionate dry powder formulation equivalents) and a LABA
4. Morning pre-BD FEV1 value of ≥40 and \<80% value (\<90% for patients 12 to 17 years of age) of their PNV.
5. Post-BD reversibility of ≥12% and ≥200 mL in FEV1
6. ACQ-6 score ≥1.5

Exclusion Criteria:

1. Pulmonary disease other than asthma
2. History of anaphylaxis following any biologic therapy
3. Hepatitis B, C or HIV
4. Pregnant or breastfeeding
5. History of cancer
6. Current tobacco smoking or a history of tobacco smoking for ≥ 10 pack-years
7. Previous receipt of tralokinumab

Primary outcomes:
measure: Annualised Asthma Exacerbation Rate (AAER) up to Week 52
timeFrame: Baseline (Week 0) up to Week 52
Secondary outcomes:
measure: Percent Change From Baseline to Week 52 in Pre-dose/Pre-bronchodilator (BD) Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline (Week 0) and Week 52
measure: Change From Baseline to Week 52 in Total Asthma Symptom Score (Bi-weekly Means)
timeFrame: Baseline (Week 0) and Week 52
measure: Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score
timeFrame: Baseline (Week 0) and Week 52
measure: Change From Baseline to Week 52 in Asthma Control Questionnaire-6 (ACQ-6) Score
timeFrame: Baseline (Week 0) and Week 52
measure: AAER Associated With an ER/UC Visit, or a Hospitalisation up to Week 52
timeFrame: Baseline (Week 0) up to Week 52
measure: Change From Baseline in European Quality of Life - 5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Scores at Week 52
timeFrame: Baseline (Week 0) and Week 52
measure: Change From Baseline in Total Asthma Rescue Medication Use at Week 52 (Bi-weekly Means)
timeFrame: Baseline (Week 0) and Week 52
measure: Change From Baseline in Home Peak Expiratory Flow (PEF) (Morning and Evening) at Week 52
timeFrame: Baseline (Week 0) and Week 52
measure: Change From Baseline in Night-time Awakenings Due to Asthma Requiring Rescue Medication Use at Week 52 (Bi-weekly Means [Percentage])
timeFrame: Baseline (Week 0) and Week 52
measure: Number of Patients With ≥1 Asthma Exacerbation up to Week 52
timeFrame: Baseline (Week 0) up to Week 52
measure: Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questions (WPAI+CIQ): Productivity Loss at Week 52
timeFrame: At Week 52
measure: WPAI+CIQ: Activity Impairment at Week 52
timeFrame: At Week 52
measure: Asthma-related Healthcare Encounters by Type up to Week 52
timeFrame: Baseline (Week 0) up to Week 52
measure: Asthma-related Healthcare Encounters by Type up to Week 52: Hospitalisations
timeFrame: Baseline (Week 0) up to Week 52
measure: Asthma-related Healthcare Encounters by Type up to Week 52: Spirometry
timeFrame: Baseline (Week 0) up to Week 52
measure: Serum Trough Concentration (Ctrough) of Tralokinumab During the Treatment Period up to Week 72
timeFrame: Blood samples were collected pre-dose at Baseline (Week 0), and at Week 2, Week 8, Week 26, Week 56 (follow-up) and Week 72 (follow-up)
measure: Incidence Rate of Positive Anti-drug Antibodies (ADAs) Including the Characterization of Their Neutralizing Potential
timeFrame: Baseline (Week 0), Week 26, Week 56 (follow-up) and Week 72 (follow-up)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Hoover
country: United States
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state: Alabama
city: Huntsville
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state: Alabama
city: Scottsdale
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state: Arizona
city: Little Rock
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city: Bakersfield
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city: Buena Park
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city: Palmdale
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city: Roseville
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city: Charlotte
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city: Salt Lake City
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city: Greenfield
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city: Madison
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city: Sherwood Park
country: Canada
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city: Vancouver
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state: British Columbia
city: Ajax
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city: Ajax
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city: Burlington
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city: London
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city: Windsor
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state: Quebec
city: Quebec City
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city: St Charles Borromee
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city: Saskatoon
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city: Brandys nad Labem
country: Czechia
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city: Jindrichuv Hradec
country: Czechia
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city: Praha 10 - Strasnice
country: Czechia
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city: Praha
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city: Rokycany
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city: Teplice
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city: Catania
country: Italy
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city: Genova
country: Italy
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city: Legnago
country: Italy
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city: Messina
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country: Italy
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city: Napoli
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city: Palermo
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city: Pisa
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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city: Guadalajara
country: Mexico
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country: Mexico
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country: Mexico
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city: Caloocan City
country: Philippines
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city: Iloilo City
country: Philippines
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city: Lipa City
country: Philippines
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city: Pasig City
country: Philippines
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city: Quezon City
country: Philippines
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city: Quezon City
country: Philippines
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city: San Fernando
country: Philippines
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
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city: Izhevsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Petrozavodsk
country: Russian Federation
facility: Research Site
city: Pyatigorsk
country: Russian Federation
facility: Research Site
city: Saint - Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saratov
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Ulyanovsk
country: Russian Federation
facility: Research Site
city: Vladikavkaz
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Boksburg North
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Mount Edgecombe
country: South Africa
facility: Research Site
city: Mowbray
country: South Africa
facility: Research Site
city: Port Elizabeth
country: South Africa
facility: Research Site
city: Stanger
country: South Africa
facility: Research Site
city: Kaohsiung Hsien
country: Taiwan
facility: Research Site
city: Keelung
country: Taiwan
facility: Research Site
city: New-Taipei
country: Taiwan
facility: Research Site
city: Cherkasy
country: Ukraine
facility: Research Site
city: Dnipropetrovsk
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kremenchuk
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
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city: Odesa
country: Ukraine
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city: Sumy
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
city: Uzhgorod
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
city: Bradford
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Chertsey
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Northwood
country: United Kingdom
facility: Research Site
city: Sidcup
country: United Kingdom
facility: Research Site
city: Wishaw
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Institute for Lung Health, United Kingdom
name: Christopher Brightling, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gottlow M, Svensson DJ, Lipkovich I, Huhn M, Bowen K, Wessman P, Colice G. Application of structured statistical analyses to identify a biomarker predictive of enhanced tralokinumab efficacy in phase III clinical trials for severe, uncontrolled asthma. BMC Pulm Med. 2019 Jul 17;19(1):129. doi: 10.1186/s12890-019-0889-4.
citation: Carlsson M, Braddock M, Li Y, Wang J, Xu W, White N, Megally A, Hunter G, Colice G. Evaluation of Antibody Properties and Clinically Relevant Immunogenicity, Anaphylaxis, and Hypersensitivity Reactions in Two Phase III Trials of Tralokinumab in Severe, Uncontrolled Asthma. Drug Saf. 2019 Jun;42(6):769-784. doi: 10.1007/s40264-018-00788-w.
citation: Panettieri RA Jr, Sjobring U, Peterffy A, Wessman P, Bowen K, Piper E, Colice G, Brightling CE. Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials. Lancet Respir Med. 2018 Jul;6(7):511-525. doi: 10.1016/S2213-2600(18)30184-X. Epub 2018 May 20.
citation: Panettieri RA Jr, Wang M, Braddock M, Bowen K, Colice G. Tralokinumab for the treatment of severe, uncontrolled asthma: the ATMOSPHERE clinical development program. Immunotherapy. 2018 Mar 1;10(6):473-490. doi: 10.2217/imt-2017-0191. Epub 2018 Mar 14.