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

Asthma Clinical Trial

— SWIFT-2  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04718103
• Other study ID #: 213744
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 4, 2021
• Est. completion date: April 9, 2024

Study information

• Verified date: October 2023
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 397
• Est. completion date: April 9, 2024
• Est. primary completion date: April 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• GSK3511294 (Depemokimab)
GSK3511294 (Depemokimab) will be administered using a pre-filled syringe.
• Placebo
Placebo will be administered as normal saline using a pre-filled syringe.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Adelaide	South Australia
Australia	GSK Investigational Site	Coffs Harbour	New South Wales
Australia	GSK Investigational Site	South Brisbane	Queensland
Canada	GSK Investigational Site	Burlington	Ontario
Canada	GSK Investigational Site	Kelowna	British Columbia
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Sherwood Park	Alberta
Czechia	GSK Investigational Site	Tabor
Czechia	GSK Investigational Site	Teplice
France	GSK Investigational Site	Annecy Cedex
France	GSK Investigational Site	Caen
France	GSK Investigational Site	Cannes Cedex
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Strasbourg Cedex
Hungary	GSK Investigational Site	Debrecen
Hungary	GSK Investigational Site	Gödöllo
Hungary	GSK Investigational Site	Hajdunanas
Hungary	GSK Investigational Site	Mosonmagyarovar
Hungary	GSK Investigational Site	Szigetvar
Hungary	GSK Investigational Site	Szombathely
Italy	GSK Investigational Site	Brescia	Lombardia
Italy	GSK Investigational Site	Foggia	Puglia
Italy	GSK Investigational Site	Messina	Sicilia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Monserrato	Sardegna
Italy	GSK Investigational Site	Palermo	Sicilia
Italy	GSK Investigational Site	Pietra Ligure (SV)	Liguria
Italy	GSK Investigational Site	Rozzano (MI)	Lombardia
Italy	GSK Investigational Site	Salerno	Campania
Italy	GSK Investigational Site	Siena	Toscana
Italy	GSK Investigational Site	Trieste	Friuli-Venezia-Giulia
Italy	GSK Investigational Site	Varese	Lombardia
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Fukui
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukushima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Niigata
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Saga
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Ostrowiec Swietokrzyski
Poland	GSK Investigational Site	Rzeszow
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Zawadzkie
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Basurto/Bilbao
Spain	GSK Investigational Site	Benalmádena
Spain	GSK Investigational Site	Elche
Spain	GSK Investigational Site	Esplugues de Llobregat
Spain	GSK Investigational Site	Gerona
Spain	GSK Investigational Site	Jerez de la Frontera
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Málaga
Spain	GSK Investigational Site	Pozuelo De Alarcón	Madrid
Spain	GSK Investigational Site	Sán Crístobál De Lá Láguná
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Zaragoza
Taiwan	GSK Investigational Site	Changhua
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	New Taipei City
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Tainan
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taoyuan
United States	GSK Investigational Site	Alabaster	Alabama
United States	GSK Investigational Site	Allen	Texas
United States	GSK Investigational Site	Altoona	Pennsylvania
United States	GSK Investigational Site	Aventura	Florida
United States	GSK Investigational Site	Bellingham	Washington
United States	GSK Investigational Site	Boerne	Texas
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Burlington	Massachusetts
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dearborn	Michigan
United States	GSK Investigational Site	DuBois	Pennsylvania
United States	GSK Investigational Site	Edmond	Oklahoma
United States	GSK Investigational Site	Glenview	Illinois
United States	GSK Investigational Site	Hendersonville	Tennessee
United States	GSK Investigational Site	Hershey	Pennsylvania
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Huntersville	North Carolina
United States	GSK Investigational Site	Lafayette	Colorado
United States	GSK Investigational Site	Lancaster	California
United States	GSK Investigational Site	Livingston	New Jersey
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami Lakes	Florida
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	Mobile	Alabama
United States	GSK Investigational Site	Northfield	New Jersey
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Rapid City	South Dakota
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Stockbridge	Georgia
United States	GSK Investigational Site	Sugar Hill	Georgia
United States	GSK Investigational Site	Toms River	New Jersey
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	Iqvia Pty Ltd

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  France,  Hungary,  Italy,  Japan,  Poland,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized rate of clinically significant exacerbations over 52 weeks		Up to Week 52
Secondary	Change from Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) total score at Week 52	The SGRQ is a well-established instrument, comprising 50 items designed to measure Quality of Life in participants with diseases of airway obstruction. It consists of two parts: Part 1 produces the symptom score and Part 2 produces the activity and impact score. A Total score is also calculated which summarizes the impact of the disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and zero indicates best possible health status. Higher scores indicate worse quality of life.	Baseline (Day 1) and at Week 52
Secondary	Change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score at Week 52	The ACQ-5 is a five-item questionnaire, which has been developed as a measure of participants' asthma control that can be quickly and easily completed. The five questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, and shortness of breath, wheeze) over the previous week. The response options for all these questions consist of a zero (no impairment/limitation) to six (total impairment/ limitation) scale. Higher score indicates more limitations.	Baseline (Day 1) and at Week 52
Secondary	Change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at Week 52	FEV1 will be measured using spirometry.	Baseline (Day 1) and at Week 52
Secondary	Annualized rate of exacerbations requiring hospitalization and/or Emergency Department (ED) visit over 52 weeks		Up to Week 52