Placebo-controlled Efficacy and Safety Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-1)

A 52-week, Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre Study of the Efficacy and Safety of GSK3511294 Adjunctive Therapy in Adult and Adolescent Participants With Severe Uncontrolled Asthma With an Eosinophilic Phenotype

This is a multi-center, randomized, placebo-controlled, double-blind, parallel group study that aims to assess the efficacy and safety of GSK3511294 (Depemokimab) in participants with severe uncontrolled asthma with an eosinophilic phenotype

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Biological: GSK3511294 (Depemokimab); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 395
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1G 3Y8
    • GSK Investigational Site
  • Ontario
    • Ajax, Ontario, Canada, L1S 2J5
      • GSK Investigational Site
    • Niagara Falls, Ontario, Canada, L2H 1H5
      • GSK Investigational Site
    • Ottawa, Ontario, Canada, K1G 6C6
      • GSK Investigational Site
    • Windsor, Ontario, Canada, N8X 1T3
      • GSK Investigational Site
• China
  • Changchun, China, 130021
    • GSK Investigational Site
  • Changchun, China, 132011
    • GSK Investigational Site
  • Changsha, China, 410013
    • GSK Investigational Site
  • Chengdu, China, 610041
    • GSK Investigational Site
  • Guangzhou, China, 510120
    • GSK Investigational Site
  • Guangzhou, China, 500000
    • GSK Investigational Site
  • Guangzhou, China, 510115
    • GSK Investigational Site
  • Guangzhou, China, 510150
    • GSK Investigational Site
  • Hangzhou, China, 310009
    • GSK Investigational Site
  • Hefei, China, 230001
    • GSK Investigational Site
  • Hohhot, China, 010050
    • GSK Investigational Site
  • Huhhot, China, 010017
    • GSK Investigational Site
  • Jinan, China, 250014
    • GSK Investigational Site
  • Sanya, China, 570311
    • GSK Investigational Site
  • Shanghai, China, 200040
    • GSK Investigational Site
  • Shanghai, China, 200065
    • GSK Investigational Site
  • Shanghai, China, 200090
    • GSK Investigational Site
  • Shenyang, China, 110004
    • GSK Investigational Site
  • Shenyang, China, 110016
    • GSK Investigational Site
  • Shenzhen, China, 518020
    • GSK Investigational Site
  • Urumqi, China, 830054
    • GSK Investigational Site
  • Wenzhou, China, 325000
    • GSK Investigational Site
  • Wuhan, China, 430030
    • GSK Investigational Site
  • Xi'an, China, 710061
    • GSK Investigational Site
  • Xuzhou, China, 221006
    • GSK Investigational Site
  • Zhanjiang, China, 524000
    • GSK Investigational Site
• Czechia
  • Brno, Czechia, 625 00
    • GSK Investigational Site
  • Hradec Kralove, Czechia, 50333
    • GSK Investigational Site
  • Jindrichuv Hradec, Czechia, 377 01
    • GSK Investigational Site
  • Olomouc, Czechia, 779 00
    • GSK Investigational Site
  • Strakonice, Czechia, 386 01
    • GSK Investigational Site
• France
  • BesanCon, France, 25030
    • GSK Investigational Site
  • Cholet, France, 49300
    • GSK Investigational Site
  • Marseille, France, 13003
    • GSK Investigational Site
  • Montpellier cedex, France, 34295
    • GSK Investigational Site
  • Nice, France, 06001
    • GSK Investigational Site
  • Tarbes cedex 9, France, 65013
    • GSK Investigational Site
• Germany
  • Aschaffenburg, Germany, 63739
    • GSK Investigational Site
  • Berlin, Germany, 10367
    • GSK Investigational Site
  • Frankfurt, Germany, 60389
    • GSK Investigational Site
  • Hamburg, Germany, 22299
    • GSK Investigational Site
  • Koblenz, Germany, 56068
    • GSK Investigational Site
  • Leipzig, Germany, 04275
    • GSK Investigational Site
  • Leipzig, Germany, 04357
    • GSK Investigational Site
  • Magdeburg, Germany, 39120
    • GSK Investigational Site
  • Mainz, Germany, 60549
    • GSK Investigational Site
  • Neu-Isenburg, Germany, 63263
    • GSK Investigational Site
  • Schleswig, Germany, 24837
    • GSK Investigational Site
• Ireland
  • Cork, Ireland, 00000
    • GSK Investigational Site
  • Dublin 9, Ireland, D09 V2N0
    • GSK Investigational Site
• Italy
  • Bergamo, Italy, 24127
    • GSK Investigational Site
  • Milano, Italy, 20122
    • GSK Investigational Site
  • Modena, Italy, 41124
    • GSK Investigational Site
  • Pavia, Italy, 27100
    • GSK Investigational Site
  • Roma, Italy, 00168
    • GSK Investigational Site
  • Vicenza, Italy, 36100
    • GSK Investigational Site
• Poland
  • Kielce, Poland, 25-355
    • GSK Investigational Site
  • Krakow, Poland, 30-033
    • GSK Investigational Site
  • Lodz, Poland, 90-242
    • GSK Investigational Site
  • Lublin, Poland, 20-552
    • GSK Investigational Site
  • Strzelce Opolskie, Poland, 47-120
    • GSK Investigational Site
  • Tarnow, Poland, 33-100
    • GSK Investigational Site
  • Wroclaw, Poland, 54-239
    • GSK Investigational Site
  • Wroclaw, Poland, 53-201
    • GSK Investigational Site
• Russian Federation
  • Kemerovo, Russian Federation, 650002
    • GSK Investigational Site
  • Moscow, Russian Federation, 115093
    • GSK Investigational Site
  • Moscow, Russian Federation, 123995
    • GSK Investigational Site
  • Novosibirsk, Russian Federation, 630008
    • GSK Investigational Site
  • Saint Petersburg, Russian Federation, 191025
    • GSK Investigational Site
  • Saint-Petersburg, Russian Federation, 197022
    • GSK Investigational Site
  • St Petersburg, Russian Federation, 193312
    • GSK Investigational Site
  • Yaroslavl, Russian Federation, 150047
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Barcelona, Spain, 08006
    • GSK Investigational Site
  • BenalmAdena, Spain, 29631
    • GSK Investigational Site
  • Gerona, Spain, 17005
    • GSK Investigational Site
  • Granada, Spain, 18014
    • GSK Investigational Site
  • Madrid, Spain, 28031
    • GSK Investigational Site
  • Palma de Mallorca, Spain, 07010
    • GSK Investigational Site
  • Santa Cruz de Tenerife, Spain, 38010
    • GSK Investigational Site
  • Valencia, Spain, 46017
    • GSK Investigational Site
  • Valencia, Spain, 46015
    • GSK Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • GSK Investigational Site
  • Bradford, United Kingdom, BD9 6RJ
    • GSK Investigational Site
  • Chertsey, United Kingdom, KT16 0PZ
    • GSK Investigational Site
  • London, United Kingdom, EC1M 6BQ
    • GSK Investigational Site
  • Manchester, United Kingdom, M8 5RB
    • GSK Investigational Site
  • Nottingham, United Kingdom, NG5 1PB
    • GSK Investigational Site
• United States
  • California
    • Encinitas, California, United States, 92024
      • GSK Investigational Site
    • Long Beach, California, United States, 90806
      • GSK Investigational Site
    • Pasadena, California, United States, 91105
      • GSK Investigational Site
    • Rancho Cucamonga, California, United States, 91730
      • GSK Investigational Site
    • San Jose, California, United States, 95117
      • GSK Investigational Site
  • Florida
    • Coral Gables, Florida, United States, 33134
      • GSK Investigational Site
    • Loxahatchee Groves, Florida, United States, 33470-9272
      • GSK Investigational Site
    • Miami, Florida, United States, 33125
      • GSK Investigational Site
    • Miami, Florida, United States, 33144
      • GSK Investigational Site
    • New Port Richey, Florida, United States, 34655
      • GSK Investigational Site
    • Orlando, Florida, United States, 32806
      • GSK Investigational Site
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • GSK Investigational Site
    • Calhoun, Georgia, United States, 30103
      • GSK Investigational Site
    • Columbus, Georgia, United States, 31326
      • GSK Investigational Site
    • Savannah, Georgia, United States, 31406
      • GSK Investigational Site
  • Illinois
    • Normal, Illinois, United States, 61761
      • GSK Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • GSK Investigational Site
    • Owensboro, Kentucky, United States, 42301
      • GSK Investigational Site
  • Michigan
    • Rochester Hills, Michigan, United States, 48507
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89123
      • GSK Investigational Site
  • New York
    • Bronx, New York, United States, 10459-2417
      • GSK Investigational Site
    • New York, New York, United States, 10036
      • GSK Investigational Site
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • GSK Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • GSK Investigational Site
  • Texas
    • Boerne, Texas, United States, 78006
      • GSK Investigational Site
    • Cypress, Texas, United States, 77429
      • GSK Investigational Site
    • Cypress, Texas, United States, 77099
      • GSK Investigational Site
    • Dallas, Texas, United States, 75235
      • GSK Investigational Site
    • Kerrville, Texas, United States, 78028
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78258
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key inclusion Criteria:

• Adults and adolescents greater than or equal to (>=)12 years of age, at the time of signing the informed consent/assent.

• Participants must have a documented physician diagnosis of asthma for >=2 years that meets the National Heart, Lung, and Blood Institute (NHLBI) guidelines or Global Initiative for Asthma (GINA) guidelines and

  1. Have, or with high likelihood of having, asthma with an eosinophilic phenotype
  2. Have previously confirmed history of >=2 exacerbations requiring treatment with systemic corticosteroid (CS) (intramuscular [IM], intravenous [IV], or oral), in the 12 months prior to Visit 1, despite the use of medium to high-dose ICS. For participants receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold dose increase or greater.

• Persistent airflow obstruction as indicated by:

  1. For participants >=18 years of age at Visit 1, a pre-bronchodilator FEV1 less than (<)80% predicted (The Third National Health and Nutrition Examination Survey [NHANES III]) recorded at Visit 1

  2. For participants 12-17 years of age at Visit 1:

     • A pre-bronchodilator FEV1 <90% predicted (NHANES III) recorded at Visit 1 OR
     • FEV1:Forced Vital Capacity (FVC) ratio <0.8 recorded at Visit 1.
• 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 (GINA). Participants who are treated with medium dose ICS will also need to be treated with LABA to qualify for inclusion.
• Current treatment with at least one additional controller medication, besides ICS, for at least 3 months (for example [e.g.], LABA, LAMA, leukotriene receptor antagonist [LTRA], or theophylline).

Key randomization inclusion criteria:

• For blood eosinophilic count:

  1. An elevated peripheral blood eosinophil count of >=300 cells/microliter (mcL) demonstrated in the past 12 months prior to Visit 1 that is related to asthma OR
  2. An elevated peripheral blood eosinophil count of >=150 cells/mcL at Screening Visit 1 that is related to asthma.

• Evidence of airway reversibility or responsiveness as documented by either:

  1. Airway reversibility (FEV1>=12% and 200 milliliters [mL]) demonstrated at Visit 1 or Visit 2 using the Maximum Post Bronchodilator Procedure OR
  2. Airway reversibility (FEV1>=12% and 200 mL) documented in the 24 months prior to Visit 2 (randomization visit) OR
  3. Airway hyperresponsiveness (methacholine: Provocative concentration causing a 20% fall in FEV1 [PC20] of <8 milligrams (mg)/mL, histamine: PD20 of <7.8 micromoles, mannitol: decrease in FEV1 as per the labelled product instructions) documented in the 24 months prior to Visit 2 (randomization visit).

Key exclusion Criteria:

• 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 must be excluded prior to enrolment.
• Participants who have received mepolizumab (Nucala), reslizumab (Cinqair/Cinqaero), or benralizumab (Fasenra) within 12 months prior to Visit 1 or who have a previous documented failure with anti-IL-5/5 receptor (R) therapy.
• Participants who have received omalizumab (Xolair) or dupilumab (Dupixent) within 130 days prior to Visit.
• Participants who have received any monoclonal antibody (mAb) within 5 half-lives of Visit 1.
• Previously participated in any study with mepolizumab, reslizumab, or benralizumab and received study intervention (including placebo) within 12 months prior to Visit 1.
• The QT interval corrected 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 = [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 the excipients of GSK3511294 or a any mAb or biologic.

Key radomization exclusion criteria:

• QTcF >=450 msec or QTcF >=480 msec for participants with Bundle Branch Block, at randomization Visit 2 are excluded. Participants are excluded if an abnormal ECG finding from the 12-lead ECG conducted at Screening Visit 1 is considered to be clinically significant and would impact the participant's participation during the study, based on the evaluation of the Investigator.
• 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 .
• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK3511294; Participants received a 100 milligram (mg) dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	Biological: GSK3511294 (Depemokimab); GSK3511294 (Depemokimab) will be administered using a pre-filled syringe.
Placebo Comparator: Placebo; Participants received placebo subcutaneous (SC) injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma standard of care (SOC) treatment throughout the study.	Drug: Placebo; Matching placebo will be administered as a normal saline using a pre-filled syringe.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Rate of Clinically Significant Exacerbations up to 52 Weeks	Clinically significant exacerbations recorded were defined as worsening of asthma requiring the use of systemic corticosteroids (CS) [such as intramuscular (IM), intravenous (IV) or oral] and/or hospitalization and/or Emergency Department (ED) visit. For all participants, IV or oral steroids (e.g., prednisone) for at least 3 days or a single IM corticosteroid dose is required. For participants on maintenance systemic corticosteroids, at least double the existing maintenance dose for at least 3 days is required. Exacerbations recorded in the electronic case report form (eCRF) were considered as verified clinically significant exacerbations and included in the primary analysis. Exacerbations separated by less than 7 days was treated as a continuation of the same exacerbation.	Up to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52	The SGRQ is a 50-item patient-reported outcome tool used to measure Quality of Life in participants with airway obstruction diseases. The questions are designed to be self-completed by the participant. The total score was calculated by the symptom score, activity and impact score; and summarizing the impact of the disease on overall health status on 0-100 rating scale. Scores are expressed as a percentage of overall impairment where 100 representing worst possible health status and 0 indicating best possible health status. Higher scores indicating greater impairment of quality of life. Change from Baseline was defined as value at the indicated time point minus Baseline value.	Baseline (Day 1) and Week 52
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Week 52	The ACQ-5 is a five-item questionnaire developed as a measure of participants asthma symptom control. The questions are designed to be self-completed by the participant. The 5 questions enquired to recall how their asthma had been during the previous week and to respond about the frequency and/or severity of symptoms (nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheezing). The overall ACQ-5 response option is the mean score of all 5 questions representing 0 with no impairment/limitation and 6 as total impairment/ limitation. Higher scores indicated more limitations and lower score with better asthma control. Change from Baseline was defined as value at the indicated time point minus Baseline value.	Baseline (Day 1) and Week 52
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) At Week 52	Forced Expiratory Volume in One Second (FEV1) is defined as the volume of air that can be forced out in one second after taking a deep breath by a person and will be measured by spirometry testing. Change from Baseline in clinic pre-bronchodilator FEV1 was determined. Change from Baseline was defined as value at the indicated time point minus Baseline value.	Baseline (Day 1) and Week 52
Change From Baseline in Asthma Nighttime Symptom Diary (ANSD) Weekly Mean Score at Week 52	The ANSD is a 6-item self-administered patient reported diary developed by Patient Related Outcomes (PRO) Consortium's Asthma Working Group to facilitate comprehensive and reliable assessment of asthma symptoms from a participant's perspective. Participants were required to rate the severity of symptoms in 3 core categories: breathing symptoms (wheezing, shortness of breath), chest symptoms (chest tightness, chest pain) and cough. The ANSD was to be completed before going to bed and refers to asthma symptoms during the day. Symptoms are rated at their worst using an 11-point numeric rating scale ranging from 0 (None) to 10 (As bad as you can imagine). Higher scores indicate more severe symptoms. Mean daily scores of ANSD was calculated by weekly intervals. The baseline values were defined as the average score from Day -7 to Day -1 inclusive (at least 4 days must be non-missing). Change from Baseline was defined as value at each time point minus Baseline value.	Baseline to Week 52
Change From Baseline in Asthma Daily Symptom Diary (ADSD) Weekly Mean Score at Week 52	The ADSD is a 6-item self-administered patient reported diary developed by patient related outcomes (PRO) Consortium's Asthma Working Group to facilitate comprehensive and reliable assessment of asthma symptoms from a participant's perspective. Participants were required to rate the severity of symptoms in 3 core categories: breathing symptoms (wheezing, shortness of breath), chest symptoms (chest tightness, chest pain) and cough. The ADSD was to be completed upon waking and refers to asthma symptoms during the night-time. Symptoms are rated at their worst using an 11-point numeric rating scale ranging from 0 (None) to 10 (As bad as you can imagine). Higher scores indicate more severe symptoms. Mean daily scores of ADSD was calculated by weekly intervals. The baseline values were defined as the average score from Day -7 to Day -1 inclusive (at least 4 days must be non-missing). Change from Baseline was defined as value at each time point minus Baseline value.	Baseline to Week 52
Annualized Rate of Exacerbations Requiring Hospitalization and/or Emergency Department (ED) Visit up to 52 Weeks	The data did not meet the condition (total of 20 or more exacerbations requiring hospitalization and/or ED visit) for conducting the statistical analysis. The number of exacerbations requiring Hospitalization and/or ED Visit are reported here.	Up to Week 52

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: IQVIA Pty Ltd
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Actual): November 21, 2023
• Study Completion (Actual): November 21, 2023

Study Registration Dates

• First Submitted: January 18, 2021
• First Submitted That Met QC Criteria: January 18, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: GSK3511294 (Depemokimab); Eosinophilic phenotype; Exacerbations; Placebo; Severe uncontrolled asthma
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma
• Other Study ID Numbers: 206713

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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