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History of Changes for Study: NCT04718389
A Study of GSK3511294 Compared With Mepolizumab or Benralizumab in Participants With Severe Asthma With an Eosinophilic Phenotype
Latest version (submitted April 29, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 18, 2021 None (earliest Version on record)
2 February 22, 2021 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 June 26, 2021 Arms and Interventions, Study Status, Contacts/Locations, Conditions, Study Description and Study Identification
4 October 5, 2021 Study Status and Contacts/Locations
5 March 11, 2022 Contacts/Locations and Study Status
6 July 1, 2022 Contacts/Locations and Study Status
7 October 21, 2022 Contacts/Locations and Study Status
8 December 5, 2022 Contacts/Locations and Study Status
9 December 6, 2022 Contacts/Locations and Study Status
10 January 19, 2023 Contacts/Locations and Study Status
11 February 24, 2023 Contacts/Locations, Study Status and Study Identification
12 November 6, 2023 Contacts/Locations and Study Status
13 April 25, 2024 Contacts/Locations and Study Status
14 April 29, 2024 Study Status and Contacts/Locations
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Study NCT04718389
Submitted Date:  January 18, 2021 (v1)

Open or close this module Study Identification
Unique Protocol ID: 206785
Brief Title: A Study of GSK3511294 Compared With Mepolizumab or Benralizumab in Participants With Severe Asthma With an Eosinophilic Phenotype
Official Title: A 52-week, Randomised, Double-blind, Double-dummy, Parallel Group, Multi-centre, Non-inferiority Study Assessing Exacerbation Rate, Additional Measures of Asthma Control and Safety in Adult and Adolescent Severe Asthmatic Participants With an Eosinophilic Phenotype Treated With GSK3511294 Compared With Mepolizumab or Benralizumab
Secondary IDs:
Open or close this module Study Status
Record Verification: December 2020
Overall Status: Not yet recruiting
Study Start: January 26, 2021
Primary Completion: December 15, 2023 [Anticipated]
Study Completion: December 15, 2023 [Anticipated]
First Submitted: January 18, 2021
First Submitted that
Met QC Criteria:
January 18, 2021
First Posted: January 22, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
January 18, 2021
Last Update Posted: January 22, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: GlaxoSmithKline
Responsible Party: Sponsor
Collaborators: Iqvia Pty Ltd
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: Yes
Unapproved/Uncleared Device:
Pediatric Postmarket Surveillance:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This study will assess whether switching participants who have benefitted from mepolizumab or benralizumab to GSK3511294 is non-inferior to maintaining current treatment on the annualized rate of clinically significant exacerbations in participants with severe asthma with an eosinophilic phenotype. Throughout the study, all participants will continue their non-biologic Baseline standard of care (SoC) asthma treatment.
Detailed Description:
Open or close this module Conditions
Conditions: Asthma
Keywords: Asthma
GSK3511294
Mepolizumab
Benralizumab
Interventional
Eosinophilic phenotype
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
This is randomized, double-blind, parallel group, multi-center and non-inferiority study.
Number of Arms: 2
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 1700 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Participants receiving GSK3511294 plus placebo matching prior anti-IL-5/5R treatment
Participants will receive GSK3511294 plus placebo treatment matching the active comparator (participant's anti-Interleukin-5/ 5 receptor [anti-IL-5/5R] treatment prior to randomization): either placebo matching mepolizumab or placebo matching benralizumab. All participants will continue their non-biologic Baseline SoC asthma treatment throughout the study.
Biological: GSK3511294
GSK3511294 will be provided in a single-use prefilled syringe (PFS).
Biological: Placebo
Placebo will be a sterile liquid formulation.
Drug: Standard of care (SoC)
Non-biologic SoC will include inhaled corticosteroid (ICS) plus at least one other controller, long-acting beta-2-agonist (LABA), long-acting muscarinic antagonist (LAMA), with or without maintenance oral corticosteroids (OCS).
Device: Pre-filled Syringes (PFS)
PFS will include glass barrel with pre-staked needle and plunger.
Active Comparator: Participants receiving prior anti-IL-5/5R treatment plus placebo matching GSK3511294
Participants will receive active comparator (participant's anti-IL-5/5R treatment prior to randomization): either mepolizumab or benralizumab, plus placebo matching GSK3511294. All participants will continue their non-biologic Baseline SoC asthma treatment throughout the study.
Biological: Mepolizumab
Mepolizumab will be provided in a single-use PFS.
Biological: Benralizumab
Benralizumab will be provided in a single-use PFS.
Biological: Placebo
Placebo will be a sterile liquid formulation.
Drug: Standard of care (SoC)
Non-biologic SoC will include inhaled corticosteroid (ICS) plus at least one other controller, long-acting beta-2-agonist (LABA), long-acting muscarinic antagonist (LAMA), with or without maintenance oral corticosteroids (OCS).
Device: Pre-filled Syringes (PFS)
PFS will include glass barrel with pre-staked needle and plunger.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Annualized rate of clinically significant exacerbations over 52 weeks
[ Time Frame: Up to Week 52 ]

Clinically significant exacerbations of asthma are defined by worsening of asthma which requires use of systemic corticosteroids and/or hospitalization and/or Emergency Department (ED) visit. Annualized rate of exacerbations will be calculated as number of exacerbations experienced by the participant divided by the length of time the participant is measured on.
Secondary Outcome Measures:
1. Weighted mean change from Baseline in St. George's Respiratory Questionnaire (SGRQ) total score
[ Time Frame: Baseline (Day 1) and up to Week 52 ]

The SGRQ is a well-established instrument, comprising 51 questions designed to measure Quality of Life in participants with diseases of airway obstruction. Higher score indicates worse quality of life.
2. Weighted mean change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score
[ Time Frame: Baseline (Day 1) and up to Week 52 ]

The ACQ-5 is a five-item questionnaire, which has been developed as a measure of participants' asthma control that can be quickly and easily completed. The five questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, and shortness of breath, wheeze) over the previous week. The response options for all these questions consist of a zero (no impairment/limitation) to six (total impairment/ limitation) scale. Higher score indicates more limitations.
3. Weighted mean change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1)
[ Time Frame: Baseline (Day 1) and up to Week 52 ]

FEV1 is a measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 will be measured using spirometry.
Open or close this module Eligibility
Minimum Age: 12 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Key inclusion criteria for study:

  • Adult and adolescent participants more than or equal to (>=)12 years of age, at the time of signing the informed consent/assent.
  • Participants who have a documented physician diagnosis of asthma for >=2 years that meets the National Heart, Lung, and Blood Institute guidelines (NHLBI) or Global Initiative for Asthma (GINA) guidelines.
  • Participants receiving either mepolizumab 100 milligrams (mg) or benralizumab 30 mg for >=12 months prior to screening and have a documented benefit to therapy assessed by either:

    (i) >=50% reduction in exacerbation frequency since initiating treatment, or (ii) >=50% reduction in maintenance OCS use since initiating treatment, or (iii) No exacerbations in the past 6 months whilst receiving anti-IL-5/5R therapy and an Asthma Control Questionnaire (ACQ)-5 score of less than or equal to (<=)1.5 at screening.

  • A well-documented requirement for regular treatment with medium to high dose ICS in the 12 months prior to Visit 1 with or without maintenance OCS. The maintenance ICS dose must be >=440 micrograms (mcg) fluticasone propionate (FP) hydrofluoroalkane (HFA) product daily, or clinically comparable. Participants who are treated with medium dose ICS will also need to be treated with a LABA to qualify for inclusion.
  • Current treatment with at least one additional controller medication, besides ICS [for example (e.g.), LABA, LAMA, leukotriene receptor antagonist (LTRA), or theophylline].

Key exclusion criteria for study:

  • Participants with presence of a known pre-existing, clinically important lung condition other than asthma. This includes (but is not limited to) current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
  • Participants with other conditions that could lead to elevated eosinophils such as hyper-eosinophilic syndromes including (but not limited to) Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly known as Churg-Strauss Syndrome) or Eosinophilic Esophagitis.
  • A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Participants that had localized carcinoma of the skin which was resected for cure will not be excluded).
  • Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.
  • Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis excluded prior to enrolment.
  • Participants who have received Omalizumab (Xolair), dupilumab (Dupixent) or reslizumab (Cinqair/Cinqaero) within 130 days prior to Visit 1.
  • Participants who have received any Monoclonal antibody (mAb) within 5 half-lives of Visit 1.
  • Corrected QT interval using Fridericia's formula (QTcF) >=450 milliseconds (msec) or QTcF >=480 msec for participants with Bundle Branch Block at screening Visit 1.
  • Current smokers or former smokers with a smoking history of >=10 pack years (number of pack years equal to [number of cigarettes per day/20] times number of years smoked). A former smoker is defined as a participant who quit smoking at least 6 months prior to Visit 1.
  • Participants with allergy/intolerance to a mAb or biologic.

Key exclusion criteria for randomization:

  • Evidence of a clinically significant abnormality in the 12-lead electrocardiogram (ECG) over-read conducted at Screening Visit 1, based on the evaluation of the investigator, or QTcF >=450 msec or QTcF >=480 msec for participants with Bundle Branch Block, at randomization Visit 2.
  • Participants with a clinically significant asthma exacerbation in the 7 days prior to randomization should have their randomization visit delayed until the investigator considers the participant's asthma to be stable. If the 8-week screening period has elapsed, then the participant should be considered a run-in failure.
  • Any changes in the dose or regimen of Baseline ICS and/or additional controller medication (except for treatment of an exacerbation) during the run-in period.
Open or close this module Contacts/Locations
Central Contact Person: US GSK Clinical Trials Call Center
Telephone: 877-379-3718
Email: GSKClinicalSupportHD@gsk.com
Central Contact Backup: EU GSK Clinical Trials Call Center
Telephone: +44 (0) 20 89904466
Email: GSKClinicalSupportHD@gsk.com
Study Officials: GSK Clinical Trials
Study Director
GlaxoSmithKline
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes
IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Information:
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame:
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria:
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Open or close this module References
Citations:
Links:
Available IPD/Information:

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