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

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)

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Biological: Tralokinumab; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels (Anderlecht), Belgium, 1070
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Hasselt, Belgium, 3500
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Woluwé-St-Lambert, Belgium, 1200
    • Research Site
• France
  • GRENOBLE Cedex 9, France, 38043
    • Research Site
  • Lille Cedex, France, 59037
    • Research Site
  • Lyon Cedex 04, France, 69317
    • Research Site
  • Nantes Cedex 1, France, 44093
    • Research Site
  • Pessac, France, 33604
    • Research Site
• Germany
  • Berlin, Germany, 10717
    • Research Site
  • Berlin, Germany, 10969
    • Research Site
  • Frankfurt, Germany, 60596
    • Research Site
  • Hamburg, Germany, 22299
    • Research Site
  • Hannover, Germany, 30625
    • Research Site
  • Mainz, Germany, 55131
    • Research Site
  • München, Germany, 80331
    • Research Site
  • München-Pasing, Germany, 81241
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Research Site
  • Groningen, Netherlands, 9728 NT
    • Research Site
  • Leeuwarden, Netherlands, 8934 AD
    • Research Site
• Poland
  • Bystra Śląska, Poland, 43-360
    • Research Site
  • Kraków, Poland, 31-011
    • Research Site
  • Kraków, Poland, 31-209
    • Research Site
  • Lubin, Poland, 59-300
    • Research Site
  • Ostrowiec Świętokrzyski, Poland, 27-400
    • Research Site
  • Rzeszów, Poland, 35-051
    • Research Site
  • Wrocław, Poland, 53-301
    • Research Site
  • Wrocław, Poland, 50-220
    • Research Site
  • Łódź, Poland, 90-141
    • Research Site
• Ukraine
  • Dnipro, Ukraine, 49007
    • Research Site
  • Kharkiv, Ukraine, 61002
    • Research Site
  • Kharkiv, Ukraine, 61035
    • Research Site
  • Kyiv, Ukraine, 03680
    • Research Site
  • Kyiv, Ukraine, 04201
    • Research Site
  • Vinnytsia, Ukraine, 21001
    • Research Site
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Research Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Research Site
  • New York
    • Bronx, New York, United States, 10461
      • Research Site
    • Rochester, New York, United States, 14618
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Research Site
  • Pennsylvania
    • Monroeville, Pennsylvania, United States, 15146
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Research Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Research Site
    • Spartanburg, South Carolina, United States, 29303
      • Research Site
  • Texas
    • Boerne, Texas, United States, 78006
      • Research Site
    • Dallas, Texas, United States, 75246
      • Research Site
    • San Antonio, Texas, United States, 78212
      • Research Site
    • Tyler, Texas, United States, 75708
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23225
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo subcutaneous injection	Other: Placebo; Placebo dose
Experimental: Tralokinumab; Tralokinumab subcutaneous injection	Biological: Tralokinumab; Tralokinumab dose

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: William W Busse, M.D., University of Wisconsin School of Medicine and Public Health, Department of Medicine, Allergy & Immunology

Publications and helpful links

General Publications

• 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.
• Busse WW, Brusselle GG, Korn S, Kuna P, Magnan A, Cohen D, Bowen K, Piechowiak T, Wang MM, Colice G. Tralokinumab did not demonstrate oral corticosteroid-sparing effects in severe asthma. Eur Respir J. 2019 Jan 31;53(2):1800948. doi: 10.1183/13993003.00948-2018. Print 2019 Feb.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2015
• Primary Completion (Actual): September 7, 2017
• Study Completion (Actual): September 7, 2017

Study Registration Dates

• First Submitted: October 30, 2014
• First Submitted That Met QC Criteria: October 31, 2014
• First Posted (Estimate): November 2, 2014

Study Record Updates

• Last Update Posted (Actual): March 15, 2019
• Last Update Submitted That Met QC Criteria: February 27, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Asthma; Lung Diseases; Reactive Airways; Repiratory Tract Disease; Obstructive Lung Disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: D2210C00013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No