Clinical trial NCT04718103: A Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Eosinophilic phenotype
Exacerbations
GSK3511294 (Depemokimab)
Placebo
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2021-01-22
Enrollment: 397
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized in a 2:1 ratio to receive either GSK3511294 (Depemokimab) or placebo as an adjunct therapy.
Primary purpose: TREATMENT

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.


Eligibility criteria: Key inclusion criteria for study:

* 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

  1. Eosinophilic phenotype: participants who have, or with high likelihood of having, asthma with an eosinophilic phenotype as per randomization criteria, and
  2. 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.

* 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 fluticasone propionate (FP) hydrofluoroalkane product (HFA) daily, or clinically comparable (GINA, 2020). 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 inclusion criteria for randomization:

* 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).

Key exclusion criteria for study:

* 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.

Key exclusion criteria for randomization:

* 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.
* 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.

Primary outcomes:
measure: Annualized Rate of Clinically Significant Exacerbations up to 52 Weeks
timeFrame: Up to Week 52
Secondary outcomes:
measure: Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52
timeFrame: Baseline (Day 1) and Week 52
measure: Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Week 52
timeFrame: Baseline (Day 1) and Week 52
measure: Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) At Week 52
timeFrame: Baseline (Day 1) and Week 52
measure: Change From Baseline in Asthma Nighttime Symptom Diary (ANSD) Weekly Mean Score at Week 52
timeFrame: Baseline to Week 52
measure: Change From Baseline in Asthma Daily Symptom Diary (ADSD) Weekly Mean Score at Week 52
timeFrame: Baseline to Week 52
measure: Annualized Rate of Exacerbations Requiring Hospitalization and/or Emergency Department (ED) Visit up to 52 Weeks
timeFrame: Up to Week 52
Other outcomes:
Locations:
city: Alabaster
country: United States
facility: GSK Investigational Site
state: Alabama
city: Mobile
country: United States
facility: GSK Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Beverly Hills
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state: California
city: Lancaster
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state: California
city: Colorado Springs
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facility: GSK Investigational Site
state: Colorado
city: Lafayette
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state: Colorado
city: Aventura
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facility: GSK Investigational Site
state: Florida
city: Hialeah
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facility: GSK Investigational Site
state: Florida
city: Miami Lakes
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facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
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state: Georgia
city: Evanston
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facility: GSK Investigational Site
state: Illinois
city: Columbia
country: United States
facility: GSK Investigational Site
state: Maryland
city: Dearborn
country: United States
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state: Michigan
city: Ypsilanti
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state: Michigan
city: Saint Louis
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state: Missouri
city: Northfield
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state: New Jersey
city: Toms River
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city: Bronx
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state: New York
city: Huntersville
country: United States
facility: GSK Investigational Site
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city: Winston-Salem
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facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cincinnati
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state: Ohio
city: Edmond
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state: Oklahoma
city: Altoona
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city: Philadelphia
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city: Rapid City
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state: South Dakota
city: Allen
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state: Texas
city: Boerne
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state: Texas
city: Dallas
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state: Texas
city: Houston
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city: San Antonio
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city: San Antonio
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state: Washington
city: Milwaukee
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state: Wisconsin
city: Coffs Harbour
country: Australia
facility: GSK Investigational Site
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city: South Brisbane
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facility: GSK Investigational Site
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city: Sherwood Park
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facility: GSK Investigational Site
state: Alberta
city: Kamloops
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facility: GSK Investigational Site
state: British Columbia
city: Burlington
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facility: GSK Investigational Site
state: Ontario
city: Quebec City
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state: Quebec
city: Windsor
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city: Tabor
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city: Teplice
country: Czechia
facility: GSK Investigational Site
city: Annecy Cedex
country: France
facility: GSK Investigational Site
city: Caen cedex 9
country: France
facility: GSK Investigational Site
city: Cannes
country: France
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city: Marseille
country: France
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city: Paris
country: France
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city: Strasbourg
country: France
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city: GOdOll?
country: Hungary
facility: GSK Investigational Site
city: Mosonmagyarovar
country: Hungary
facility: GSK Investigational Site
city: Szigetvar
country: Hungary
facility: GSK Investigational Site
city: Brescia
country: Italy
facility: GSK Investigational Site
city: Foggia
country: Italy
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city: Messina
country: Italy
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city: Monserrato CA
country: Italy
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city: Palermo
country: Italy
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city: Pietra Ligure SV
country: Italy
facility: GSK Investigational Site
city: Rozzano MI
country: Italy
facility: GSK Investigational Site
city: Salerno
country: Italy
facility: GSK Investigational Site
city: Siena
country: Italy
facility: GSK Investigational Site
city: Tradate VA
country: Italy
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Aichi
country: Japan
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city: Chiba
country: Japan
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city: Ehime
country: Japan
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city: Fukui
country: Japan
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city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
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city: Fukuoka
country: Japan
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city: Fukuoka
country: Japan
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city: Fukushima
country: Japan
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city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
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city: Hokkaido
country: Japan
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city: Hyogo
country: Japan
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city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Niigata
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Saga
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Ostrowiec Swietokrzyski
country: Poland
facility: GSK Investigational Site
city: Rzeszow
country: Poland
facility: GSK Investigational Site
city: Strzelce Opolskie
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: AlmerIa
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Bilbao
country: Spain
facility: GSK Investigational Site
city: Gerona
country: Spain
facility: GSK Investigational Site
city: Jerez de la Frontera
country: Spain
facility: GSK Investigational Site
city: La Laguna Santa Cruz
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: Pozuelo De AlarcOn Madr
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: Kaohsiung
country: Taiwan
facility: GSK Investigational Site
city: Linkou - Taoyuan Hsien
country: Taiwan
facility: GSK Investigational Site
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Tainan
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.