A Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype

NCT04718103 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 213744
• Study Type: interventional
• Target: 397
• Locations: 11 countries
• Sites: 129

Brief Summary

This study will assess the efficacy and safety of GSK3511294 (Depemokimab) as an adjunctive therapy in participants with severe uncontrolled asthma with an eosinophilic phenotype.

Conditions

Asthma

Keywords

Asthma; Eosinophilic phenotype; Exacerbations; GSK3511294 (Depemokimab); 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 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.

Biological: GSK3511294

Placebo

PLACEBO COMPARATOR

Participants received placebo 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: Placebo

Interventions

GSK3511294 BIOLOGICAL

GSK3511294 was administered using a pre-filled syringe.

Also known as: Depemokimab

GSK3511294

Placebo BIOLOGICAL

Placebo was administered as 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 guidelines (NHLBI) or Global Initiative for Asthma (GINA) guidelines and
• Eosinophilic phenotype: participants who have, or with high likelihood of having, asthma with an eosinophilic phenotype as per randomization criteria, and
• Exacerbation history: participants who 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 (i) For participants \>=18 years of age at Visit 1, a pre-bronchodilator FEV1 less than (\<)80 percent (%) predicted National Health and Nutrition Examination Survey (NHANES III) recorded at Visit 1.
• (ii) 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).
• An elevated peripheral blood eosinophil count of \>=300 cells per microliter 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 per microliter at Screening Visit 1 that is related to asthma.
• Evidence of airway reversibility or responsiveness as documented by either:
• (i) Airway reversibility (FEV1\>=12% and 200 milliliter \[mL\]) demonstrated at Visit 1 or Visit 2 using the Maximum Post Bronchodilator Procedure or (ii) Airway reversibility (FEV1\>=12% and 200 mL) documented in the 24 months prior to Visit 2 (randomization visit) or (iii) Airway hyper-responsiveness (methacholine: Provocative concentration causing a 20% fall in FEV1 \[PC20\] of \<8 milligrams per milliliter (mg/mL), histamine: Provocative dose that decreases FEV1 by 20% \[PD20\] 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).

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 who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment.
• 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-Interleukin-5/Anti-Interleukin-5 receptor (anti-IL-5/5R) therapy.
• Participants who have received omalizumab (Xolair) or dupilumab (Dupixent) within 130 days prior to Visit 1.
• 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.
• 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 = \[number of cigarettes per day/ 20\] multiplied by 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 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 Electrocardiogram (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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Iqvia Pty Ltd: collaborator

Study Sites (129)

GSK Investigational Site

Alabaster, Alabama, 35007, United States

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GSK Investigational Site

Mobile, Alabama, 36608, United States

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GSK Investigational Site

Phoenix, Arizona, 85032, United States

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GSK Investigational Site

Beverly Hills, California, 90048, United States

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GSK Investigational Site

Lancaster, California, 93534, United States

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GSK Investigational Site

Colorado Springs, Colorado, 80923, United States

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GSK Investigational Site

Lafayette, Colorado, 80026, United States

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GSK Investigational Site

Aventura, Florida, 33180, United States

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GSK Investigational Site

Hialeah, Florida, 33014, United States

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GSK Investigational Site

Miami, Florida, 33144, United States

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GSK Investigational Site

Miami, Florida, 33186, United States

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GSK Investigational Site

Miami Lakes, Florida, 33014, United States

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GSK Investigational Site

Orlando, Florida, 32803, United States

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GSK Investigational Site

Atlanta, Georgia, 30281, United States

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GSK Investigational Site

Evanston, Illinois, 60026, United States

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GSK Investigational Site

Columbia, Maryland, 21044, United States

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GSK Investigational Site

Dearborn, Michigan, 48124, United States

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GSK Investigational Site

Ypsilanti, Michigan, 48197, United States

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GSK Investigational Site

St Louis, Missouri, 63110, United States

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GSK Investigational Site

Northfield, New Jersey, 08225, United States

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GSK Investigational Site

Toms River, New Jersey, 08755, United States

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GSK Investigational Site

The Bronx, New York, 10467, United States

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GSK Investigational Site

Huntersville, North Carolina, 28078, United States

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GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

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GSK Investigational Site

Cincinnati, Ohio, 45229, United States

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GSK Investigational Site

Cincinnati, Ohio, 45231, United States

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GSK Investigational Site

Edmond, Oklahoma, 73034, United States

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GSK Investigational Site

Altoona, Pennsylvania, 16601, United States

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GSK Investigational Site

DuBois, Pennsylvania, 15801, United States

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GSK Investigational Site

Hershey, Pennsylvania, 17033, United States

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GSK Investigational Site

Philadelphia, Pennsylvania, 19140, United States

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GSK Investigational Site

Rapid City, South Dakota, 57702, United States

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GSK Investigational Site

Allen, Texas, 75013, United States

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GSK Investigational Site

Boerne, Texas, 78006, United States

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GSK Investigational Site

Dallas, Texas, 75225, United States

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GSK Investigational Site

Houston, Texas, 77084, United States

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GSK Investigational Site

San Antonio, Texas, 78207, United States

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GSK Investigational Site

San Antonio, Texas, 78229, United States

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GSK Investigational Site

San Antonio, Texas, 78258, United States

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GSK Investigational Site

Bellingham, Washington, 98225, United States

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GSK Investigational Site

Milwaukee, Wisconsin, 53226, United States

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GSK Investigational Site

Coffs Harbour, New South Wales, 2450, Australia

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GSK Investigational Site

South Brisbane, Queensland, 4101, Australia

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GSK Investigational Site

Sherwood Park, Alberta, T8H 0N2, Canada

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GSK Investigational Site

Kamloops, British Columbia, V1Y 4N7, Canada

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Burlington, Ontario, L7N 3V2, Canada

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GSK Investigational Site

Québec, Quebec, G1V 4W2, Canada

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GSK Investigational Site

Windsor, 5000, Canada

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GSK Investigational Site

Jindřichův Hradec, 377 01, Czechia

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GSK Investigational Site

Tábor, 390 02, Czechia

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GSK Investigational Site

Teplice, 415 01, Czechia

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GSK Investigational Site

Annecy, 74011, France

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GSK Investigational Site

Caen, 14033, France

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GSK Investigational Site

Cannes, 06414, France

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GSK Investigational Site

Marseille, 13015, France

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GSK Investigational Site

Paris, 75014, France

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Strasbourg, 67091, France

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GSK Investigational Site

GOdOll?, 2100, Hungary

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GSK Investigational Site

Mosonmagyaróvár, 9200, Hungary

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GSK Investigational Site

Szigetvár, 7900, Hungary

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Brescia, 25123, Italy

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Foggia, 71122, Italy

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GSK Investigational Site

Messina, 98124, Italy

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GSK Investigational Site

Monserrato CA, 09042, Italy

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GSK Investigational Site

Palermo, 90127, Italy

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GSK Investigational Site

Pietra Ligure SV, 17027, Italy

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GSK Investigational Site

Rozzano MI, 20089, Italy

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GSK Investigational Site

Salerno, 84131, Italy

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GSK Investigational Site

Siena, 53100, Italy

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GSK Investigational Site

Tradate VA, 21100, Italy

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GSK Investigational Site

Aichi, 470-1192, Japan

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GSK Investigational Site

Aichi, 489-8642, Japan

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GSK Investigational Site

Chiba, 275-8580, Japan

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GSK Investigational Site

Ehime, 790-0024, Japan

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GSK Investigational Site

Fukui, 910-8526, Japan

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GSK Investigational Site

Fukuoka, 802-0052, Japan

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GSK Investigational Site

Fukuoka, 805-8508, Japan

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GSK Investigational Site

Fukuoka, 811-1394, Japan

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GSK Investigational Site

Fukuoka, 813-0017, Japan

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GSK Investigational Site

Fukushima, 960-1295, Japan

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GSK Investigational Site

Hiroshima, 734-8530, Japan

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GSK Investigational Site

Hokkaido, 053-8506, Japan

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GSK Investigational Site

Hokkaido, 064-0804, Japan

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GSK Investigational Site

Hyōgo, 653-0013, Japan

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GSK Investigational Site

Hyōgo, 670-0849, Japan

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GSK Investigational Site

Kagawa, 761-8073, Japan

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GSK Investigational Site

Kagawa, 762-8550, Japan

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GSK Investigational Site

Kagoshima, 890-8520, Japan

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GSK Investigational Site

Kanagawa, 231-8682, Japan

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GSK Investigational Site

Kanagawa, 232-0024, Japan

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GSK Investigational Site

Niigata, 951-8520, Japan

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GSK Investigational Site

Okayama, 702-8055, Japan

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GSK Investigational Site

Saga, 843-0393, Japan

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GSK Investigational Site

Shizuoka, 420-8527, Japan

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Tokyo, 103-0027, Japan

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GSK Investigational Site

Tokyo, 141-8625, Japan

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GSK Investigational Site

Tokyo, 142-8666, Japan

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GSK Investigational Site

Tokyo, 158-0097, Japan

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GSK Investigational Site

Tokyo, 185-0014, Japan

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GSK Investigational Site

Tokyo, 204-8585, Japan

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GSK Investigational Site

Gdansk, 80-214, Poland

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Krakow, 30-033, Poland

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GSK Investigational Site

Krakow, 31-624, Poland

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GSK Investigational Site

Ostrowiec Świętokrzyski, 27-400, Poland

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GSK Investigational Site

Rzeszów, 35-051, Poland

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GSK Investigational Site

Strzelce Opolskie, 47-120, Poland

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GSK Investigational Site

Wroclaw, 54-239, Poland

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GSK Investigational Site

Almería, 29631, Spain

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GSK Investigational Site

Badalona, 08916, Spain

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GSK Investigational Site

Barcelona, 08023, Spain

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Bilbao, 48013, Spain

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GSK Investigational Site

Girona, 17005, Spain

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GSK Investigational Site

Jerez de la Frontera, 11407, Spain

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GSK Investigational Site

La Laguna Santa Cruz, 38320, Spain

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GSK Investigational Site

Madrid, 28040, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Málaga, 29010, Spain

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GSK Investigational Site

Pozuelo de AlarcOn Madr, 28223, Spain

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GSK Investigational Site

Santander, 39008, Spain

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GSK Investigational Site

Santiago de Compostela, 15706, Spain

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GSK Investigational Site

Valencia, 46010, Spain

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GSK Investigational Site

Zaragoza, 50009, Spain

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GSK Investigational Site

Kaohsiung City, 807, Taiwan

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GSK Investigational Site

Linkou - Taoyuan Hsien, 333, Taiwan

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GSK Investigational Site

Taichung, 402, Taiwan

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GSK Investigational Site

Taichung, 40705, Taiwan

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GSK Investigational Site

Tainan, 704, Taiwan

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GSK Investigational Site

Taipei, 23561, Taiwan

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Related Publications (2)

• 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 BACKGROUND

• 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

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

866-435-7343

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

Model Details: Participants will be randomized in a 2:1 ratio to receive either GSK3511294 (Depemokimab) or placebo as an adjunct therapy.

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: January 22, 2021
• Study Start: February 4, 2021
• Primary Completion: April 11, 2024
• Study Completion: April 11, 2024
• Last Updated: November 29, 2024
• Results First Posted: November 29, 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, a 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

JP (30); HU (3); PL (7); ES (16); TW (6); IT (10); FR (6); US (41); CA (5); CZ (3); AU (2)