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

NCT04719832 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 206713
• Study Type: interventional
• Target: 395
• Locations: 12 countries
• Sites: 123

Brief Summary

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

Conditions

Asthma

Keywords

GSK3511294 (Depemokimab); Eosinophilic phenotype; Severe uncontrolled asthma; Exacerbations; Placebo

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52

  Baseline (Day 1) and Week 52

• Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Week 52

  Baseline (Day 1) and Week 52

• Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) At Week 52

  Baseline (Day 1) and Week 52

• Change From Baseline in Asthma Nighttime Symptom Diary (ANSD) Weekly Mean Score at Week 52

  Baseline to Week 52

• Change From Baseline in Asthma Daily Symptom Diary (ADSD) Weekly Mean Score at Week 52

  Baseline to Week 52

Study Arms (2)

GSK3511294

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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

Interventions

GSK3511294 (Depemokimab) BIOLOGICAL

GSK3511294 (Depemokimab) will be administered using a pre-filled syringe.

GSK3511294

Placebo DRUG

Matching placebo will be administered as a normal saline using a pre-filled syringe.

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Have, or with high likelihood of having, asthma with an eosinophilic phenotype
• 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:
• 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
• 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.
• 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).
• For blood eosinophilic count:
• 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
• 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:
• Airway reversibility (FEV1\>=12% and 200 milliliters \[mL\]) demonstrated at Visit 1 or Visit 2 using the Maximum Post Bronchodilator Procedure OR

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Iqvia Pty Ltd: collaborator

Study Sites (123)

GSK Investigational Site

Encinitas, California, 92024, United States

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GSK Investigational Site

Long Beach, California, 90806, United States

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GSK Investigational Site

Pasadena, California, 91105, United States

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GSK Investigational Site

Rancho Cucamonga, California, 91730, United States

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GSK Investigational Site

San Jose, California, 95117, United States

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GSK Investigational Site

Coral Gables, Florida, 33134, United States

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GSK Investigational Site

Loxahatchee Groves, Florida, 33470-9272, United States

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GSK Investigational Site

Miami, Florida, 33125, United States

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GSK Investigational Site

Miami, Florida, 33144, United States

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GSK Investigational Site

New Port Richey, Florida, 34655, United States

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GSK Investigational Site

Orlando, Florida, 32806, United States

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GSK Investigational Site

Alpharetta, Georgia, 30022, United States

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GSK Investigational Site

Calhoun, Georgia, 30103, United States

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GSK Investigational Site

Columbus, Georgia, 31326, United States

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GSK Investigational Site

Savannah, Georgia, 31406, United States

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GSK Investigational Site

Normal, Illinois, 61761, United States

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GSK Investigational Site

Lexington, Kentucky, 40509, United States

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GSK Investigational Site

Owensboro, Kentucky, 42301, United States

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Rochester Hills, Michigan, 48507, United States

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Las Vegas, Nevada, 89123, United States

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GSK Investigational Site

New York, New York, 10036, United States

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GSK Investigational Site

The Bronx, New York, 10459-2417, United States

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GSK Investigational Site

Gastonia, North Carolina, 28054, United States

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GSK Investigational Site

Cleveland, Ohio, 44106, United States

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GSK Investigational Site

Boerne, Texas, 78006, United States

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GSK Investigational Site

Cypress, Texas, 77099, United States

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GSK Investigational Site

Cypress, Texas, 77429, United States

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GSK Investigational Site

Dallas, Texas, 75235, United States

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GSK Investigational Site

Kerrville, Texas, 78028, United States

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GSK Investigational Site

San Antonio, Texas, 78258, United States

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GSK Investigational Site

Ajax, Ontario, L1S 2J5, Canada

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GSK Investigational Site

Niagara Falls, Ontario, L2H 1H5, Canada

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Ottawa, Ontario, K1G 6C6, Canada

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Windsor, Ontario, N8X 1T3, Canada

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Québec, Quebec, G1G 3Y8, Canada

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Changchun, 130021, China

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Changchun, 132011, China

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Changsha, 410013, China

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GSK Investigational Site

Chengdu, 610041, China

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GSK Investigational Site

Guangzhou, 500000, China

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GSK Investigational Site

Guangzhou, 510115, China

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GSK Investigational Site

Guangzhou, 510120, China

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GSK Investigational Site

Guangzhou, 510150, China

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GSK Investigational Site

Hangzhou, 310009, China

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GSK Investigational Site

Hefei, 230001, China

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GSK Investigational Site

Hohhot, 010017, China

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GSK Investigational Site

Hohhot, 010050, China

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GSK Investigational Site

Jinan, 250014, China

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GSK Investigational Site

Sanya, 570311, China

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GSK Investigational Site

Shanghai, 200040, China

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GSK Investigational Site

Shanghai, 200065, China

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GSK Investigational Site

Shanghai, 200090, China

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GSK Investigational Site

Shenyang, 110004, China

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GSK Investigational Site

Shenyang, 110016, China

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GSK Investigational Site

Shenzhen, 518020, China

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GSK Investigational Site

Ürümqi, 830054, China

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GSK Investigational Site

Wenzhou, 325000, China

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GSK Investigational Site

Wuhan, 430030, China

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GSK Investigational Site

Xi'an, 710061, China

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GSK Investigational Site

Xuzhou, 221006, China

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GSK Investigational Site

Zhanjiang, 524000, China

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GSK Investigational Site

Brno, 625 00, Czechia

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GSK Investigational Site

Hradec Králové, 50333, Czechia

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GSK Investigational Site

Jindřichův Hradec, 377 01, Czechia

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GSK Investigational Site

Olomouc, 779 00, Czechia

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GSK Investigational Site

Strakonice, 386 01, Czechia

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GSK Investigational Site

Besançon, 25030, France

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GSK Investigational Site

Cholet, 49300, France

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Marseille, 13003, France

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Montpellier, 34295, France

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Nice, 06001, France

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Tarbes, 65013, France

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Aschaffenburg, 63739, Germany

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Berlin, 10367, Germany

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Frankfurt, 60389, Germany

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Hamburg, 22299, Germany

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Koblenz, 56068, Germany

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GSK Investigational Site

Leipzig, 04275, Germany

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Leipzig, 04357, Germany

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Magdeburg, 39120, Germany

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Mainz, 60549, Germany

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Neu-Isenburg, 63263, Germany

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Schleswig, 24837, Germany

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Cork, 00000, Ireland

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Dublin, D09 V2N0, Ireland

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Bergamo, 24127, Italy

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GSK Investigational Site

Milan, 20122, Italy

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Modena, 41124, Italy

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GSK Investigational Site

Pavia, 27100, Italy

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GSK Investigational Site

Roma, 00168, Italy

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GSK Investigational Site

Vicenza, 36100, Italy

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GSK Investigational Site

Kielce, 25-355, Poland

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Krakow, 30-033, Poland

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Lodz, 90-242, Poland

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GSK Investigational Site

Lublin, 20-552, Poland

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GSK Investigational Site

Strzelce Opolskie, 47-120, Poland

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Tarnów, 33-100, Poland

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Wroclaw, 53-201, Poland

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GSK Investigational Site

Wroclaw, 54-239, Poland

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GSK Investigational Site

Kemerovo, 650002, Russia

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Moscow, 115093, Russia

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GSK Investigational Site

Moscow, 123995, Russia

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GSK Investigational Site

Novosibirsk, 630008, Russia

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GSK Investigational Site

Saint Petersburg, 191025, Russia

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GSK Investigational Site

Saint Petersburg, 193312, Russia

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Saint Petersburg, 197022, Russia

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GSK Investigational Site

Yaroslavl, 150047, Russia

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GSK Investigational Site

Barcelona, 08006, Spain

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GSK Investigational Site

Barcelona, 08035, Spain

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GSK Investigational Site

Benalmádena, 29631, Spain

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GSK Investigational Site

Girona, 17005, Spain

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GSK Investigational Site

Granada, 18014, Spain

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GSK Investigational Site

Madrid, 28031, Spain

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GSK Investigational Site

Palma de Mallorca, 07010, Spain

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GSK Investigational Site

Santa Cruz de Tenerife, 38010, Spain

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GSK Investigational Site

Valencia, 46015, Spain

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GSK Investigational Site

Valencia, 46017, Spain

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Birmingham, B9 5SS, United Kingdom

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GSK Investigational Site

Bradford, BD9 6RJ, United Kingdom

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GSK Investigational Site

Chertsey, KT16 0PZ, United Kingdom

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GSK Investigational Site

London, EC1M 6BQ, United Kingdom

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GSK Investigational Site

Manchester, M8 5RB, United Kingdom

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GSK Investigational Site

Nottingham, NG5 1PB, United Kingdom

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Related Publications (2)

• Jackson DJ, Bourdin A, Blackorby A, Leslie A, Vichiendilokkul A, Howarth P, Karkoszka N, Fujieda S, Cornet M. Safety and Tolerability of Twice-Yearly Depemokimab in Patients with Asthma and Chronic Rhinosinusitis with Nasal Polyps: Pooled Results from SWIFT-1/-2 and ANCHOR-1/-2. Adv Ther. 2025 Dec 29. doi: 10.1007/s12325-025-03457-4. Online ahead of print.

  PMID: 41461999 DERIVED

• Jackson DJ, Wechsler ME, Jackson DJ, Bernstein D, Korn S, Pfeffer PE, Chen R, Saito J, de Luiz Martinez G, Dymek L, Jacques L, Bird N, Schalkwijk S, Smith D, Howarth P, Pavord ID; SWIFT-1 and SWIFT-2 Investigators; SWIFT-1 Investigators; SWIFT-2 Investigators. Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype. N Engl J Med. 2024 Dec 19;391(24):2337-2349. doi: 10.1056/NEJMoa2406673. Epub 2024 Sep 9.

  PMID: 39248309 DERIVED

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

8664357343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: January 22, 2021
• Study Start: March 17, 2021
• Primary Completion: November 21, 2023
• Study Completion: November 21, 2023
• Last Updated: December 17, 2024
• Results First Posted: December 17, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

PL (8); IE (2); FR (6); IT (6); RU (8); ES (10); US (30); CN (26); GB (6); CA (5); CZ (5); DE (11)