Phase 3 Study to Evaluate the Efficacy & Safety of Tralokinumab in Adults & Adolescents With OCS Dependent Asthma

Study Overview
=================
Brief Summary
-----------------
A Multicentre, Randomized, Double-blind, Parallel Group, Placebo Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Reducing Oral Corticosteroid dependent Asthma.

Detailed Description
-----------------
This is a randomized, double-blind, parallel group, placebo-controlled study designed to evaluate the efficacy and safety of a fixed 300 mg dose of tralokinumab administered subcutaneously every 2 weeks in adult and adolescent subjects with oral corticosteroid dependent asthma. Approximately120 subjects will be randomized globally. Subjects will receive tralokinumab or placebo, administered via subcutaneous injection at the study site, over a 40-week treatment period.

Official Title
-----------------
A Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Reducing Oral Corticosteroid Use in Adults and Adolescents With Oral Corticosteroid Dependent Asthma (TROPOS)

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Biological: Tralokinumab
* Other: Placebo


Participation Criteria
=================
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 and a LABA. 4) Subjects must have received OCS for the treatment of asthma for 6 months prior to Visit 1 and on a stable OCS dose between ≥7.5 to ≤30mg daily or daily equivalent for at least one month prior to enrolment (Visit 1) . 5) Pre-BD FEV1 value <80% (<90% for patients 12-17 yrs of age) of their PNV. 6) Post-BD reversibility of ≥12% in FEV1. Exclusion Criteria: 1) Clinically important 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.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tralokinumab<br>Tralokinumab subcutaneous injection | Biological: Tralokinumab<br>* Tralokinumab dose<br>|
| Placebo Comparator: Placebo<br>Placebo subcutaneous injection | Other: Placebo<br>* Placebo dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in the Final Daily, Average, OCS Dose at Week 40 While Not Losing Asthma Control. | The 40-week treatment period consisted of 3 phases: an induction phase (Week 0 to Week 12) where patients remained on their optimised OCS dose; an OCS reduction phase (Week 12 to Week 32) where OCS dose reduction could have started at Week 12 with the possibility of dose titration every 4 weeks to reach the lowest possible OCS dose; and a maintenance phase (Week 32 to Week 40) where patients remained on the OCS dose reached at Week 32 to demonstrate asthma control was maintained after achieving the lowest OCS dose. Criteria used to assess asthma control included lung function assessments (forced expiratory volume in 1 second and morning peak expiratory flow), night awakenings, and the use of rescue medication and systemic corticosteroids. The least squares (LS) mean percent change from baseline in average daily OCS dose is presented. The final daily percent change from baseline was defined as {(Final daily average dose - baseline daily average dose)/baseline daily average dose}*100%. | Baseline (Week 0) and Week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Patients With Final Daily Average OCS Dose ≤5 mg at Week 40. | The 40-week treatment period consisted of 3 phases: an induction phase (Week 0 to Week 12) where patients remained on their optimised OCS dose; an OCS reduction phase (Week 12 to Week 32) where OCS dose reduction could have started at Week 12 with the possibility of dose titration every 4 weeks to reach the lowest possible OCS dose; and a maintenance phase (Week 32 to Week 40) where patients remained on the OCS dose reached at Week 32 to demonstrate asthma control was maintained after achieving the lowest OCS dose. The number of patients with a final daily average OCS dose ≤5.0 mg is presented. For patients prescribed a fixed daily dose, then the average OCS dose was defined as the prescribed dose. For patients on a regimen where a different amount of OCS was to be taken each day, then the average OCS dose was defined as the average amount prescribed to be taken each day. | At Week 40 | 
| The Number of Patients With ≥50% Reduction in Final Average Daily OCS Dose at Week 40. | The 40-week treatment period consisted of 3 phases: an induction phase (Week 0 to Week 12) where patients remained on their optimised OCS dose; an OCS reduction phase (Week 12 to Week 32) where OCS dose reduction could have started at Week 12 with the possibility of dose titration every 4 weeks to reach the lowest possible OCS dose; and a maintenance phase (Week 32 to Week 40) where patients remained on the OCS dose reached at Week 32 to demonstrate asthma control was maintained after achieving the lowest OCS dose. The number of patients with ≥50% reduction in average daily OCS dose is presented. The final daily percent change from baseline was defined as {(Final daily average dose - baseline daily average dose)/baseline daily average dose}*100%. If this resulted in a value of -50% or less (more negative), that patient was classified as having at least a 50% reduction in final daily average OCS dose. | At Week 40 | 
| Annual Asthma Exacerbation Rate (AAER) up to Week 40. | AAER up to Week 40 in the tralokinumab group was compared to that seen in the placebo group. The response variable was the number of exacerbations the patient experienced up to Week 40, with the logarithm of the time at risk in years of experiencing an exacerbation included as offset in the model. AAER = number of exacerbations*365.25/(follow-up date - date of randomisation + 1). 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. 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. | Baseline (Week 0) up to Week 40 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Asthma, Reactive Airways, Repiratory Tract Disease, Obstructive Lung Disease, Lung Diseases