Clinical trial NCT02161757: 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
Keywords: Asthma
Reactive Airways
Respiratory Tract Disease
Obstructive Lung Disease
Lung Diseases
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-06-12
Enrollment: 1207
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 1140 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 Study Period up to Week 72
timeFrame: Blood samples were collected pre-dose at Baseline (Week 0), and at Week 4, Week 8, Week 26, Week 52 and Week 72 (follow-up)
measure: Number of Patients Positive for Anti-drug Antibodies (ADAs)
timeFrame: Baseline (Week 0), Week 26, Week 56 (follow-up) and Week 72 (follow-up)
Other outcomes:
Locations:
city: Birmingham
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state: Alabama
city: Phoenix
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country: Korea, Republic of
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city: Cusco
country: Peru
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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city: Ostrowiec Świętokrzyski
country: Poland
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country: Poland
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city: Łódź
country: Poland
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city: Humenne
country: Slovakia
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country: Slovakia
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city: Presov
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city: Sabinov
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city: Topolcany
country: Slovakia
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city: Alicante
country: Spain
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city: Badalona
country: Spain
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city: Hospitalet de Llobregat(Barcel
country: Spain
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city: Santander
country: Spain
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city: Valencia
country: Spain
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city: Changhua
country: Taiwan
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city: Kaohsiung
country: Taiwan
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city: New-Taipei
country: Taiwan
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city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
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city: Yilan
country: Taiwan
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city: Chernivtsi
country: Ukraine
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city: Chernivtsi
country: Ukraine
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city: Ivano-Frankivsk
country: Ukraine
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city: Kharkiv
country: Ukraine
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city: Kharkiv
country: Ukraine
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country: Ukraine
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country: Ukraine
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country: Ukraine
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country: Ukraine
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country: Ukraine
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city: Vinnytsia
country: Ukraine
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city: Zaporizhzhya
country: Ukraine
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city: Zaporizhzhya
country: Ukraine
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city: Can Tho
country: Vietnam
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city: Ha Noi
country: Vietnam
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city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Hochiminh
country: Vietnam
facility: Research Site
Study officials:
affiliation: University of Pennsylvania
name: Reynold A Panettieri, M.D.
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.