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

Asthma Clinical Trial

— SWIFT-1  

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: Completed

Administrative data

• NCT number: NCT04719832
• Other study ID #: 206713
• Status: Completed
• Phase: Phase 3
• Start date: March 17, 2021
• Est. completion date: November 21, 2023

Study information

• Verified date: May 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 395
• Est. completion date: November 21, 2023
• Est. primary completion date: November 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

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

Drug:
• Placebo
Matching placebo will be administered as a normal saline using a pre-filled syringe.

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Ajax	Ontario
Canada	GSK Investigational Site	Niagara Falls	Ontario
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Québec
Canada	GSK Investigational Site	Windsor	Ontario
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Changsha	Hunan
China	GSK Investigational Site	Chengdu
China	GSK Investigational Site	Guangzhou
China	GSK Investigational Site	Guangzhou
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Haikou	Hainan
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Hefei
China	GSK Investigational Site	Hohhot	Inner Mongolia
China	GSK Investigational Site	Huhhot	Inner Mongolia
China	GSK Investigational Site	Jinan
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Shenzhen	Guangdong
China	GSK Investigational Site	Urumqi	Xinjiang
China	GSK Investigational Site	Wenzhou
China	GSK Investigational Site	Wuhan	Hubei
China	GSK Investigational Site	Xian	Shaanxi
China	GSK Investigational Site	Xuzhou	Jiangsu
China	GSK Investigational Site	Zhanjiang	Guangdong
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Hradec Kralove
Czechia	GSK Investigational Site	Jindrichuv Hradec
Czechia	GSK Investigational Site	Olomouc
Czechia	GSK Investigational Site	Strakonice
France	GSK Investigational Site	Besançon
France	GSK Investigational Site	Cholet
France	GSK Investigational Site	Marseille.
France	GSK Investigational Site	Montpellier cedex 5
France	GSK Investigational Site	Nice cedex 1
France	GSK Investigational Site	Tarbes
Germany	GSK Investigational Site	Aschaffenburg	Bayern
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bonn
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Koblenz	Rheinland-Pfalz
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Magdeburg
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Neu isenburg	Hessen
Germany	GSK Investigational Site	Schleswig	Schleswig-Holstein
Ireland	GSK Investigational Site	Cork
Ireland	GSK Investigational Site	Dublin
Italy	GSK Investigational Site	Bergamo	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Modena	Emilia-Romagna
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Roma
Italy	GSK Investigational Site	Vicenza	Veneto
Poland	GSK Investigational Site	Kielce
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Tarnow
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Zawadzkie
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Saint Petersburg
Russian Federation	GSK Investigational Site	Saint- Petersburg
Russian Federation	GSK Investigational Site	St.Petersburg
Russian Federation	GSK Investigational Site	Yaroslavl
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Benalmádena
Spain	GSK Investigational Site	Gerona
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Pama de Mallorca
Spain	GSK Investigational Site	Santa Cruz de Tenerife
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
United Kingdom	GSK Investigational Site	Birmingham
United Kingdom	GSK Investigational Site	Bradford
United Kingdom	GSK Investigational Site	Chertsey, Surrey
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Nottingham
United States	GSK Investigational Site	Adairsville	Georgia
United States	GSK Investigational Site	Alpharetta	Georgia
United States	GSK Investigational Site	Boerne	Texas
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Coral Gables	Florida
United States	GSK Investigational Site	Cypress	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Encinitas	California
United States	GSK Investigational Site	Flint	Michigan
United States	GSK Investigational Site	Gastonia	North Carolina
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Kerrville	Texas
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Loxahatchee Groves	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Normal	Illinois
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Owensboro	Kentucky
United States	GSK Investigational Site	Pasadena	California
United States	GSK Investigational Site	Rancho Cucamonga	California
United States	GSK Investigational Site	Rincon	Georgia
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Jose	California
United States	GSK Investigational Site	Savannah	Georgia
United States	GSK Investigational Site	Trinity	Florida

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	Iqvia Pty Ltd

Countries where clinical trial is conducted

United States,  Canada,  China,  Czechia,  France,  Germany,  Ireland,  Italy,  Poland,  Russian Federation,  Spain,  United Kingdom, 

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 (scores on a scale)	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 worst quality of life.	Baseline (Day 1) and Week 52
Secondary	Change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score at Week 52 (scores on a scale)	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 questions are designed to be self-completed by the participant. 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 scores indicate more limitations.	Baseline (Day 1) and Week 52
Secondary	Change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at Week 52 (liters)	FEV1 will be measured by spirometry.	Baseline (Day 1) and Week 52
Secondary	Annualized rate of exacerbations requiring hospitalization and/or Emergency department (ED) visit over 52 weeks		Up to Week 52