Clinical trial NCT04719832: Placebo-controlled Efficacy and Safety 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: GSK3511294 (Depemokimab)
Eosinophilic phenotype
Severe uncontrolled asthma
Exacerbations
Placebo
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2021-01-22
Enrollment: 395
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

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: Encinitas
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Pasadena
country: United States
facility: GSK Investigational Site
state: California
city: Rancho Cucamonga
country: United States
facility: GSK Investigational Site
state: California
city: San Jose
country: United States
facility: GSK Investigational Site
state: California
city: Coral Gables
country: United States
facility: GSK Investigational Site
state: Florida
city: Loxahatchee Groves
country: United States
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: New Port Richey
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Alpharetta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Calhoun
country: United States
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state: Georgia
city: Columbus
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state: Georgia
city: Savannah
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state: Georgia
city: Normal
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facility: GSK Investigational Site
state: Illinois
city: Lexington
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facility: GSK Investigational Site
state: Kentucky
city: Owensboro
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facility: GSK Investigational Site
state: Kentucky
city: Rochester Hills
country: United States
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state: Michigan
city: Las Vegas
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state: Nevada
city: Bronx
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state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Gastonia
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Boerne
country: United States
facility: GSK Investigational Site
state: Texas
city: Cypress
country: United States
facility: GSK Investigational Site
state: Texas
city: Cypress
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city: Dallas
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state: Texas
city: Kerrville
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state: Texas
city: Ajax
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Niagara Falls
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Windsor
country: Canada
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state: Ontario
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Changchun
country: China
facility: GSK Investigational Site
city: Changchun
country: China
facility: GSK Investigational Site
city: Changsha
country: China
facility: GSK Investigational Site
city: Chengdu
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
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city: Guangzhou
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
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city: Guangzhou
country: China
facility: GSK Investigational Site
city: Hangzhou
country: China
facility: GSK Investigational Site
city: Hefei
country: China
facility: GSK Investigational Site
city: Hohhot
country: China
facility: GSK Investigational Site
city: Huhhot
country: China
facility: GSK Investigational Site
city: Jinan
country: China
facility: GSK Investigational Site
city: Sanya
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shenyang
country: China
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city: Shenyang
country: China
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city: Shenzhen
country: China
facility: GSK Investigational Site
city: Urumqi
country: China
facility: GSK Investigational Site
city: Wenzhou
country: China
facility: GSK Investigational Site
city: Wuhan
country: China
facility: GSK Investigational Site
city: Xi'an
country: China
facility: GSK Investigational Site
city: Xuzhou
country: China
facility: GSK Investigational Site
city: Zhanjiang
country: China
facility: GSK Investigational Site
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Jindrichuv Hradec
country: Czechia
facility: GSK Investigational Site
city: Olomouc
country: Czechia
facility: GSK Investigational Site
city: Strakonice
country: Czechia
facility: GSK Investigational Site
city: BesanCon
country: France
facility: GSK Investigational Site
city: Cholet
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Montpellier cedex
country: France
facility: GSK Investigational Site
city: Nice
country: France
facility: GSK Investigational Site
city: Tarbes cedex 9
country: France
facility: GSK Investigational Site
city: Aschaffenburg
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Frankfurt
country: Germany
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city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Koblenz
country: Germany
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city: Leipzig
country: Germany
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city: Leipzig
country: Germany
facility: GSK Investigational Site
city: Magdeburg
country: Germany
facility: GSK Investigational Site
city: Mainz
country: Germany
facility: GSK Investigational Site
city: Neu-Isenburg
country: Germany
facility: GSK Investigational Site
city: Schleswig
country: Germany
facility: GSK Investigational Site
city: Cork
country: Ireland
facility: GSK Investigational Site
city: Dublin 9
country: Ireland
facility: GSK Investigational Site
city: Bergamo
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Modena
country: Italy
facility: GSK Investigational Site
city: Pavia
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Vicenza
country: Italy
facility: GSK Investigational Site
city: Kielce
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Strzelce Opolskie
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Kemerovo
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Novosibirsk
country: Russian Federation
facility: GSK Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: BenalmAdena
country: Spain
facility: GSK Investigational Site
city: Gerona
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Palma de Mallorca
country: Spain
facility: GSK Investigational Site
city: Santa Cruz de Tenerife
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Bradford
country: United Kingdom
facility: GSK Investigational Site
city: Chertsey
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: