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

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ClinicalTrials.gov Identifier: NCT04719832
Recruitment Status : Recruiting
First Posted : January 22, 2021
Last Update Posted : June 30, 2021
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
GSK3511294 (Depemokimab) is being developed as a long-acting (LA) injectable anti-interleukin-5 (anti-IL-5) therapy and is expected to deliver an efficacy and safety profile similar to current anti-IL-5 therapies with a reduced dosing frequency. This study is a multi-center, randomized, placebo-controlled, double-blind, parallel group design and aims to assess the efficacy and safety of GSK3511294 (Depemokimab) in participants with severe uncontrolled asthma with an eosinophilic phenotype despite standard of care (SoC) treatment with medium to high dose inhaled corticosteroids (ICS) plus at least one additional controller. All participants will receive study intervention as an adjunct therapy while remaining on their existing asthma therapy throughout the study. Assessments will include the annualized rate of clinically significant exacerbations and measures of lung function, asthma control, and safety. Approximately 375 participants will be enrolled in the study.

Condition or disease Intervention/treatment Phase
Asthma Biological: GSK3511294 (Depemokimab) Drug: Placebo Drug: Standard of care Device: Pre-filled Syringe Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 375 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This study is a multi-center, randomized, placebo-controlled, double-blind, parallel group design.
Masking: Double (Participant, Investigator)
Masking Description: Participant and investigator will be blinded in the study.
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 17, 2021
Estimated Primary Completion Date : October 3, 2023
Estimated Study Completion Date : October 3, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Participants receiving GSK3511294 (Depemokimab)
Participants will be administered GSK3511294 (Depemokimab) along with SoC.
Biological: GSK3511294 (Depemokimab)
GSK3511294 (Depemokimab) will be administered.

Drug: Standard of care
SoC will include ICS plus at least one other controller, Long-acting beta-agonist (LABA), Long-acting muscarinic antagonist (LAMA), with or without maintenance oral corticosteroids (OCS).

Device: Pre-filled Syringe
Pre-filled syringe will include glass barrel with pre-staked needle and plunger.

Placebo Comparator: Participants receiving placebo
Participants will be administered matching placebo along with SoC.
Drug: Placebo
Matching placebo will be administered.

Drug: Standard of care
SoC will include ICS plus at least one other controller, Long-acting beta-agonist (LABA), Long-acting muscarinic antagonist (LAMA), with or without maintenance oral corticosteroids (OCS).

Device: Pre-filled Syringe
Pre-filled syringe will include glass barrel with pre-staked needle and plunger.




Primary Outcome Measures :
  1. Annualized rate of clinically significant exacerbations over 52 weeks [ Time Frame: Up to Week 52 ]
    Clinically significant exacerbations of asthma will be defined by worsening of asthma which requires use of systemic corticosteroids and/or hospitalization and/or Emergency Department (ED) visit. Annualized rate of exacerbations will be calculated as number of exacerbations experienced by the participant divided by the length of time the participant is measured on.


Secondary Outcome Measures :
  1. Change from Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) total score at Week 52 (scores on a scale) [ Time Frame: Baseline (Day 1) and Week 52 ]
    The SGRQ is a well-established instrument, comprising 51 questions 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.

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

  3. Change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at Week 52 (liters) [ Time Frame: Baseline (Day 1) and Week 52 ]
    FEV1 is defined as the volume of air that can be forced out in one second after taking a deep breath by a person and will be measured by spirometry. Change from Baseline in clinic pre and post-bronchodilator FEV1 will be determined.

  4. Annualized rate of exacerbations requiring hospitalization and/or ED visit over 52 weeks [ Time Frame: Up to Week 52 ]
    Annualized rate of exacerbations requiring hospitalization and/or ED visit will be assessed. Annualized rate of exacerbations will be calculated as number of exacerbations experienced by the participant divided by the length of time the participant is measured on.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • 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 12 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 12 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 a mAb or biologic.

Key radomization exclusion criteria:

  • Evidence of a clinically significant abnormality in the 12-lead electrocardiogram (ECG) over-read conducted at Screening Visit 1, based on the evaluation of the investigator, OR QTcF >=450 msec or QTcF >=480 msec for participants with Bundle Branch Block, at randomization Visit 2.
  • 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.

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): NCT04719832


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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United States, California
GSK Investigational Site Recruiting
Long Beach, California, United States, 90808
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Steven M Meltzer         
GSK Investigational Site Recruiting
Pasadena, California, United States, 91105
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: John De Beixedon         
GSK Investigational Site Recruiting
Rancho Cucamonga, California, United States, 91730
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Javier Chang         
GSK Investigational Site Recruiting
San Jose, California, United States, 95117
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Alan B Goldsobel         
United States, Florida
GSK Investigational Site Recruiting
Coral Gables, Florida, United States, 33134
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Jorge R Beato         
GSK Investigational Site Recruiting
Kissimmee, Florida, United States, 34741
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Thomas O'Brien         
GSK Investigational Site Recruiting
Loxahatchee Groves, Florida, United States, 33470-9272
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Neal Warshoff         
GSK Investigational Site Recruiting
Miami, Florida, United States, 33144
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Orlando Rivero         
GSK Investigational Site Recruiting
Orlando, Florida, United States, 32806
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Michael Anderson         
United States, Georgia
GSK Investigational Site Recruiting
Alpharetta, Georgia, United States, 30022
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Vasundhara Cheekati         
GSK Investigational Site Recruiting
Calhoun, Georgia, United States, 30701
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: John Trimble         
GSK Investigational Site Recruiting
Rincon, Georgia, United States, 31326
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Maria Mascolo         
GSK Investigational Site Recruiting
Savannah, Georgia, United States, 31406
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Brad H. Goodman         
United States, Illinois
GSK Investigational Site Recruiting
Normal, Illinois, United States, 61761
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Dareen Siri         
United States, Kentucky
GSK Investigational Site Recruiting
Owensboro, Kentucky, United States, 42301
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Lee S Clore         
United States, Nevada
GSK Investigational Site Recruiting
Las Vegas, Nevada, United States, 89123
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Yekaterina Khronusova         
United States, New York
GSK Investigational Site Recruiting
New York, New York, United States, 10036
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: James Edward Greenwald         
United States, North Carolina
GSK Investigational Site Recruiting
Gastonia, North Carolina, United States, 28054
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Anup Banerjee         
United States, Rhode Island
GSK Investigational Site Recruiting
Warwick, Rhode Island, United States, 02886
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: John F Zwetchkenbaum         
United States, Texas
GSK Investigational Site Recruiting
Boerne, Texas, United States, 78006
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: David Fuentes         
GSK Investigational Site Recruiting
Kerrville, Texas, United States, 78028
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Dale Mohar         
GSK Investigational Site Recruiting
San Antonio, Texas, United States, 78258
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Brian MacGillivray         
Sponsors and Collaborators
GlaxoSmithKline
Iqvia Pty Ltd
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04719832    
Other Study ID Numbers: 206713
First Posted: January 22, 2021    Key Record Dates
Last Update Posted: June 30, 2021
Last Verified: June 2021
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, 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: Yes
Keywords provided by GlaxoSmithKline:
GSK3511294 (Depemokimab)
Eosinophilic phenotype
Severe uncontrolled asthma
Inhaled corticosteroids
Standard of care
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