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

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ClinicalTrials.gov Identifier: NCT04718103
Recruitment Status : Recruiting
First Posted : January 22, 2021
Last Update Posted : February 14, 2023
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
GlaxoSmithKline

Study Description
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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.

Condition or disease Intervention/treatment Phase
Asthma Biological: GSK3511294 (Depemokimab) Biological: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 375 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomized in a 2:1 ratio to receive either GSK3511294 (Depemokimab) or placebo as an adjunct therapy.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : March 11, 2021
Estimated Primary Completion Date : May 24, 2024
Estimated Study Completion Date : May 24, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Participants receiving GSK3511294 (Depemokimab) Biological: GSK3511294 (Depemokimab)
GSK3511294 (Depemokimab) will be administered using a pre-filled syringe.
Placebo Comparator: Participants receiving Placebo Biological: Placebo
Placebo will be administered as normal saline using a pre-filled syringe.


Outcome Measures
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Primary Outcome Measures :
  1. Annualized rate of clinically significant exacerbations over 52 weeks [ Time Frame: Up to Week 52 ]

Secondary Outcome Measures :
  1. Change from Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) total score at Week 52 [ Time Frame: Baseline (Day 1) and 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.

  2. Change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score at Week 52 [ Time Frame: Baseline (Day 1) and 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.

  3. Change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at Week 52 [ Time Frame: Baseline (Day 1) and at Week 52 ]
    FEV1 will be measured using spirometry.

  4. Annualized rate of exacerbations requiring hospitalization and/or Emergency Department (ED) visit over 52 weeks [ Time Frame: Up to Week 52 ]

Eligibility Criteria
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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04718103


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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Sponsors and Collaborators
GlaxoSmithKline
Iqvia Pty Ltd
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04718103    
Other Study ID Numbers: 213744
First Posted: January 22, 2021    Key Record Dates
Last Update Posted: February 14, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Asthma
Eosinophilic phenotype
Exacerbations
GSK3511294 (Depemokimab)
Placebo
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
 Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases