Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults and Adolescents With Uncontrolled Asthma (STRATOS2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02194699
Recruitment Status : Completed
First Posted : July 18, 2014
Results First Posted : March 21, 2018
Last Update Posted : May 15, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE July 17, 2014
First Posted Date  ICMJE July 18, 2014
Results First Submitted Date  ICMJE February 23, 2018
Results First Posted Date  ICMJE March 21, 2018
Last Update Posted Date May 15, 2018
Actual Study Start Date  ICMJE October 30, 2014
Actual Primary Completion Date May 10, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 23, 2018)
Annualised Asthma Exacerbation Rate (AAER) up to Week 52 [ Time Frame: Baseline (Week 0) up to Week 52 ]
Asthma exacerbation was defined as a worsening of asthma that led to any of the following:
  • Use of systemic corticosteroids for at least 3 days; a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids.
  • An emergency room (ER) or urgent care (UC) visit (defined as evaluation and treatment for <24 hours in an ER or UC centre) due to asthma that required systemic corticosteroids (see above).
  • An inpatient hospitalisation (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours) due to asthma.
AAER = number of exacerbations*365.25 / (follow-up date - date of randomisation + 1) (where maximum follow-up time for a patient was approximately 52 weeks). AAER in the tralokinumab group was compared to that seen in the placebo group up to Week 52 using a negative binomial model; rate ratios and rate reductions are both presented for comparative statistical analyses.
Original Primary Outcome Measures  ICMJE
 (submitted: July 17, 2014)
Annual asthma exacerbation rate [ Time Frame: Week 0 to Week 52 ]
To evaluate the effect of tralokinumab compared with placebo on the annualised asthma exacerbation rate in adult and adolescent subjects with asthma that is inadequately controlled with inhaled corticosteroid plus long-acting β2-agonist
Change History Complete list of historical versions of study NCT02194699 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2018)
  • Percent Change From Baseline to Week 52 in Pre-dose/Pre-bronchodilator (BD) Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline (Week 0) and Week 52 ]
    Lung function was assessed by FEV1 which was measured by spirometry. Spirometry was performed by the Investigator or authorised delegate according to American Thoracic Society/European Respiratory Society guidelines. The mean percent change from baseline in pre-BD FEV1 at Week 52 is presented.
  • Change From Baseline to Week 52 in Total Asthma Symptom Score (Bi-weekly Means) [ Time Frame: Baseline (Week 0) and Week 52 ]
    Asthma symptoms during night-time and daytime were recorded by the patient each morning and evening in the Asthma Daily Diary. Symptoms were recorded using a 4-point response scale, which ranged from 0 to 3, where 0 indicated no asthma symptoms. Asthma symptom daytime score (recorded in the evening), night-time score (recorded in the morning), and total score were calculated separately. The daily asthma symptom total score was calculated by taking the sum of the night-time and daytime asthma symptom scores recorded each day, ranging from 0 to 6. A lower symptom score indicated a better outcome. The change from baseline in bi-weekly mean daily asthma symptom total score is presented.
  • Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score [ Time Frame: Baseline (Week 0) and Week 52 ]
    The AQLQ(S)+12 is a questionnaire that measures health-related quality of life for patients with asthma aged 12 and older. The questionnaire comprises 32 questions and has 4 separate domains (asthma symptoms, activity limitations, emotional function and environmental stimuli). Patients were asked to recall their experiences during the previous 2 weeks and to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The total score was calculated as the mean response to all questions, ranging from 1 (severe impairment) to 7 (no impairment). Individual AQLQ(S)+12 total score changes of ≥0.5 were considered to be clinically meaningful. The mean change from baseline in AQLQ(S)+12 score at Week 52 is presented.
  • Change From Baseline to Week 52 in Asthma Control Questionnaire-6 (ACQ-6) Score [ Time Frame: Baseline (Week 0) and Week 52 ]
    The ACQ-6 questionnaire is a shortened version of the ACQ (omitting FEV1 measurement) that assesses asthma symptoms (night-time awakenings, symptoms on waking, activity limitation, dyspnoea, wheezing) and rescue short-acting β2-agonists medication use during the past week. Questions were weighted equally and scored on a 7-point scale from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score was the mean of the responses, ranging from 0 (totally controlled) to 6 (severely uncontrolled). Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma and a score >1.5 indicates not well-controlled asthma. Individual changes of at least 0.5 were considered to be clinically meaningful. The mean change from baseline in ACQ-6 score at Week 52 is presented.
  • AAER Associated With an ER/UC Visit, or a Hospitalisation up to Week 52 [ Time Frame: Baseline (Week 0) up to Week 52 ]
    The annual rate of exacerbations associated with an ER/UC visit or hospitalisation up to Week 52 are presented for non-adjudicated data (i.e. events assessed by the Investigator and recorded in the electronic case report form). AAER = number of exacerbations*365.25 / (follow-up date - date of randomisation + 1) (where maximum follow-up time for a patient was approximately 52 weeks).
  • Change From Baseline in European Quality of Life - 5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Scores at Week 52 [ Time Frame: Baseline (Week 0) and Week 52 ]
    The EQ-5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The patient was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. The questionnaire also included a VAS, where the patient was asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state. The mean change from baseline in EQ-5D-5L VAS scores at Week 52 is presented.
  • Change From Baseline in Total Asthma Rescue Medication Use at Week 52 (Bi-weekly Means) [ Time Frame: Baseline (Week 0) and Week 52 ]
    Salbutamol, albuterol or levalbuterol were used as rescue medication during the study in the event of a worsening of asthma symptoms. Rescue medication use was measured by the bi-weekly mean number of inhalations (puffs) per day, calculated as: total morning puffs + total evening puffs + 2*(total morning nebuliser use + total evening nebuliser use)/ total number of days with data in bi-weekly period. The change from baseline in bi-weekly mean total asthma rescue medication use at Week 52 is presented.
  • Change From Baseline in Home Peak Expiratory Flow (PEF) (Morning and Evening) at Week 52 [ Time Frame: Baseline (Week 0) and Week 52 ]
    Home PEF testing was performed by the patient using an electronic, hand-held spirometer (peak flow meter) and was performed in the morning upon awakening (prior to taking their morning asthma controller) and in the evening at bedtime (prior to taking their evening asthma controller). The mean change from baseline in home PEF values at Week 52 are presented separately for morning and evening.
  • Change From Baseline in Night-time Awakenings Due to Asthma Requiring Rescue Medication Use at Week 52 (Bi-weekly Means [Percentage]) [ Time Frame: Baseline (Week 0) and Week 52 ]
    The patient captured night-time awakenings (yes/no) and the use of rescue medication during these awakenings (yes/no) each morning in the Asthma Daily Diary. Night-time awakenings (percentage) was defined as the number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data. The change from baseline in bi-weekly means (percentage) night-time awakenings due to asthma requiring rescue medication use at Week 52 is presented.
  • Number of Patients With ≥1 Asthma Exacerbation up to Week 52 [ Time Frame: Baseline (Week 0) up to Week 52 ]
    The number of patients with ≥1 asthma exacerbation up to Week 52 is presented.
  • Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questions (WPAI+CIQ): Productivity Loss at Week 52 [ Time Frame: At Week 52 ]
    The WPAI+CIQ consists of questions about how asthma and asthma-related issues impact a patient's ability to work, attend classes and perform regular daily activities. The questionnaire contains 10 questions relating to the patient's experience over the previous 7 days. The WPAI+CIQ outcomes for productivity loss are presented separately for those currently employed and for those currently in school and are expressed as mean productivity loss (percentage) at Week 52, with higher numbers indicating less productivity. Work Productivity Loss = {Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)]}*100 (Absenteeism = Q2/(Q2+Q4)*100; Presenteeism = (Q5/10)*100). Class Productivity Loss = {Q7/(Q7+Q8) + [(1-Q7/(Q7+Q8))x(Q9/10)]}*100 (Absenteeism = Q7/(Q7+Q8)*100; Presenteeism = (Q9/10)*100). Note: QX refers to response to question number X on WPAI+CIQ questionnaire.
  • WPAI+CIQ: Activity Impairment at Week 52 [ Time Frame: At Week 52 ]
    The WPAI+CIQ consists of questions about how asthma and asthma-related issues impact a patient's ability to work, attend classes and perform regular daily activities. The questionnaire contains 10 questions relating to the patient's experience over the previous 7 days. The WPAI+CIQ outcomes for activity impairment are presented separately for those currently employed and for those currently in school and are expressed as mean impairment percentages at Week 52, with higher numbers indicating greater impairment. Activity impairment = (Q10/10)*100. Note: QX refers to response to question number X on WPAI+CIQ questionnaire.
  • Asthma-related Healthcare Encounters by Type up to Week 52 [ Time Frame: Baseline (Week 0) up to Week 52 ]
    Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of 'since the last scheduled visit'. Total number of times the healthcare encounter occurred was calculated across all patients for each of the following categories:
    • Ambulance transport,
    • Emergency room visits,
    • Unscheduled outpatient visits (visit to specialist and/or visit to primary healthcare physician and/or other healthcare visit),
    • Home visits (home visit, physician and/or other healthcare professional),
    • Telephone calls (telephone calls to physician and/or nurse), and
    • Advanced pulmonary function test.
  • Asthma-related Healthcare Encounters by Type up to Week 52: Hospitalisations [ Time Frame: Baseline (Week 0) up to Week 52 ]
    Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of 'since the last scheduled visit'. Total number of days spent in hospital was calculated across all patients for the following healthcare encounter category: • Hospitalisations (hospitalisations, intensive care and/or general care).
  • Asthma-related Healthcare Encounters by Type up to Week 52: Spirometry [ Time Frame: Baseline (Week 0) up to Week 52 ]
    Broad-based healthcare utilisation asthma-related event information was collected by the Investigator/authorised delegate at each visit. At Visit 1, healthcare resource utilisation information was collected with a 1-year recall period; subsequent visits collected information with a recall period of 'since the last scheduled visit'. Total number of assessments was calculated across all patients for the following healthcare encounter category: • Spirometry.
  • Serum Trough Concentration (Ctrough) of Tralokinumab During the Treatment Period up to Week 72 [ Time Frame: 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) ]
    To evaluate the pharmacokinetics (PK), pre-dose blood samples were collected at each visit and tralokinumab concentrations in serum were determined. Mean Ctrough concentrations are presented at each indicated visit up to Week 72.
  • Incidence Rate of Positive Anti-drug Antibodies (ADAs) Including the Characterization of Their Neutralizing Potential [ Time Frame: Baseline (Week 0), Week 26, Week 56 (follow-up) and Week 72 (follow-up) ]
    Assessments of ADA were performed using a tiered approach (screening, confirmatory and titering assays). Confirmed ADA positive samples were also tested for the presence of neutralising antibodies (nAb). ADA prevalence was defined as proportion of the study population having drug-reactive antibodies at any point in time. ADA incidence (treatment-emergent ADA) was defined as the sum of both treatment-induced (post-baseline ADA positive only) and treatment-boosted ADA. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted to a 4-fold or higher level following drug administration. Note: 'positive' is denoted by 'pos' in some category titles.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2014)
  • Percent change from baseline to Week 52 in pre-dose/pre-bronchodilator forced expiratory volume in 1 second [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab with regards to lung function
  • Change from baseline to Week 52 in daily asthma symptom score [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab with regards to asthma symptoms
  • Change from baseline to Week 52 in Asthma Quality of Life Questionnaire for 12 Years and Older total score [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab with regards to asthma specific health-related quality of life
  • Change from baseline to Week 52 in Asthma Control Questionnaire-6 defined asthma control [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab with regards to Asthma Control Questionnaire-6 defined asthma control
  • Annualised asthma exacerbation rate that is associated with an ER or urgent care visit, or a hospitalization [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab compared with placebo with regards to emergency room and urgent care visits and hospitalizations due to asthma
  • European Quality of Life - 5 Dimension 5 Level Daily Living Questionnaire [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab compared with placebo with regards to health related quality of life
  • Rescue medication use [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab compared with placebo with regards to asthma symptoms and asthma control as measured by rescue medication use
  • Home peak expiratory flow (morning and evening) [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab compared with placebo with regards to asthma symptoms and asthma control as measured by home peak expiratory flow
  • Night-time awakening due to asthma [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab compared with placebo with regards to asthma symptoms and asthma control as measured by night-time awakenings due to asthma
  • Time to first asthma exacerbation [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab compared with placebo with regards to asthma exacerbations as measured by time to first asthma exacerbation
  • Proportion of subjects with ≥1 asthma exacerbation [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab compared with placebo with regards to asthma exacerbations as measured by the proportion of subjects with at least one asthma exacerbation
  • Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab compared with placebo with regards to productivity loss due to asthma
  • Asthma specific resource utilization [ Time Frame: Week 0 to Week 52 ]
    To assess the effect of tralokinumab compared with placebo with regards to health care resource utilization
  • Pharmacokinetic parameters (Ctrough at steady state) [ Time Frame: Week 0 to Week 72 ]
    To evaluate the pharmacokinetics of tralokinumab
  • Incidence rate of positive anti-drug antibodies including the characterization of their neutralizing potential [ Time Frame: Week 0 to Week 72 ]
    To evaluate the immunogenicity of tralokinumab
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: July 17, 2014)
Safety and Tolerability of tralokinumab assessed by the reporting of adverse events/serious adverse events and assessments for physical [ Time Frame: Week 0 to Week 72 ]
To evaluate the safety and tolerability tralokinumab
 
Descriptive Information
Brief Title  ICMJE A Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults and Adolescents With Uncontrolled Asthma
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Uncontrolled Asthma
Intervention  ICMJE
  • Biological: Experimental: Tralokinumab
    Tralokinumab subcutaneous injection
  • Other: Placebo
    Placebo subcutaneous injection
Study Arms  ICMJE
  • Experimental: Tralokinumab
    Tralokinumab subcutaneous injection
    Intervention: Biological: Experimental: Tralokinumab
  • Placebo Comparator: Placebo
    Placebo subcutaneous injection
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 13, 2018)
856
Original Estimated Enrollment  ICMJE
 (submitted: July 17, 2014)
2200
Actual Study Completion Date  ICMJE September 21, 2017
Actual Primary Completion Date May 10, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Chile,   Czechia,   Italy,   Japan,   Mexico,   Philippines,   Russian Federation,   South Africa,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02194699
Other Study ID Numbers  ICMJE D2210C00008
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: This is commercially sensitive information.
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christopher Brightling, MD Institute for Lung Health, United Kingdom
PRS Account AstraZeneca
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP