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

Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score

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.

Time frame: Baseline (Week 0) and Week 52

Change From Baseline to Week 52 in Asthma Control Questionnaire-6 (ACQ-6) Score

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.

Time frame: Baseline (Week 0) and Week 52

AAER Associated With an ER/UC Visit, or a Hospitalisation 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).

Time frame: Baseline (Week 0) up to Week 52

Change From Baseline in European Quality of Life - 5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Scores at 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.

Time frame: Baseline (Week 0) and Week 52

Change From Baseline in Total Asthma Rescue Medication Use at Week 52 (Bi-weekly Means)

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.

Time frame: Baseline (Week 0) and Week 52

Change From Baseline in Home Peak Expiratory Flow (PEF) (Morning and Evening) at 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.

Time frame: Baseline (Week 0) and Week 52

Change From Baseline in Night-time Awakenings Due to Asthma Requiring Rescue Medication Use at Week 52 (Bi-weekly Means [Percentage])

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.

Time frame: Baseline (Week 0) and Week 52

Number of Patients With ≥1 Asthma Exacerbation up to Week 52

The number of patients with ≥1 asthma exacerbation up to Week 52 is presented.

Time frame: Baseline (Week 0) up to Week 52

Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questions (WPAI+CIQ): Productivity Loss 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.

Time frame: At Week 52

WPAI+CIQ: Activity Impairment 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.

Time frame: At Week 52

Asthma-related Healthcare Encounters by Type 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.

Time frame: Baseline (Week 0) up to Week 52

Asthma-related Healthcare Encounters by Type up to Week 52: Hospitalisations

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).

Time frame: Baseline (Week 0) up to Week 52

Asthma-related Healthcare Encounters by Type up to Week 52: Spirometry

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.

Time frame: Baseline (Week 0) up to Week 52

Serum Trough Concentration (Ctrough) of Tralokinumab During the Study Period up to Week 72

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.

Time frame: 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)

Number of Patients Positive for Anti-drug Antibodies (ADAs)

ADA assessments performed using a tiered approach (screening, confirmatory and titering assays). Confirmed ADA positive samples were also tested for neutralising antibodies (nAb). ADA prevalence defined as proportion of study population with drug-reactive antibodies at any point in time. ADA incidence (treatment-emergent ADA) defined as sum of treatment-induced (post-baseline ADA positive only) and treatment-boosted ADA. Persistently positive 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 defined as having ≥1 post-baseline ADA positive assessment and not fulfilling conditions of persistently positive. Treatment-boosted ADA defined as baseline positive ADA titer boosted to a 4-fold or higher level following drug administration. In some category titles 'positive' is denoted by 'pos'.

Time frame: Baseline (Week 0), Week 26, Week 56 (follow-up) and Week 72 (follow-up)