Asthma
Conditions
Keywords
GSK3511294, Depemokimab, MODIFY, Type 2 asthma
Brief summary
The aim of this study is to evaluate the efficacy of depemokimab administered as an adjunctive therapy, in participants with Type 2 asthma at risk of exacerbations compared to the guideline recommended standard of care (SoC).
Interventions
DRUGDepemokimab
Depemokimab will be administered
DRUGPlacebo
Placebo will be administered
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is double-blind, placebo-controlled study.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults and adolescents \>=12 years of age, at the time of signing the informed consent/assent. For countries where local regulations or the regulatory status of study medication permit enrolment of adults only, participants recruited will be \>=18 years of age. * Participants must have a documented physician diagnosis of asthma for \>=2 years that meets the National Heart, Lung, and Blood Institute, National Institute for Health and Care Excellence or Global Initiative for Asthma guidelines * Have previously confirmed history of at least 2 exacerbations over the last 3 years prior to screening, with at least 1 of those exacerbations occurring in the previous year prior to Screening Visit 1. * Exacerbation requiring treatment with systemic Corticosteroid (CS), for at least 3 days, despite the use of low to medium dose Inhaled corticosteroids (ICS)/ Long-acting beta2-adrenergic receptor agonist (LABA). * A well-documented requirement for treatment with low to medium dose ICS/LABA (in the 12 months prior to screening visit. Treatment should be stable for 3 months prior to screening. If participants are taking Maintenance and Reliever Therapy/Single Maintenance and Reliever Therapy regularly, the total daily dose should be incorporated into the assessment of low or medium dose ICS. * Study will limit enrolment to a maximum of 40 percent (%) of participants on low dose ICS/LABA. * Sex and Contraceptive/Barrier Requirements Male or eligible female Participants: * Male Participants: Contraception for male participants with female partners is not required. * Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: * Is a participant of nonchildbearing potential (PONCBP) OR * Is a participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective, with a failure rate of less than (\<)1%, from at least 14 days prior to the first dose of study intervention until at least 35 weeks after the last administered dose of study intervention. * A POCBP must have a negative highly sensitive serum pregnancy test at Screening Visit 1, Exit Visit 11 or Withdrawn from study visit, and a negative highly sensitive urine pregnancy test within 24 hours before the first dose of study intervention. * Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention). * The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. * Capable of giving signed informed consent/assent as which includes compliance with the requirements Randomization inclusion criteria- * Type 2 high disease at risk of asthma exacerbations as defined by either: * An elevated peripheral blood eosinophils (EOS) count of \>=500 cells/microliter (μL) at screening or \>=500 cells/μL in the last 3 months prior to the screening visit. OR * An elevated peripheral blood EOS count of \>=300 cells/μL at screening OR \>=300 cells/μL in the last 3 months prior to the screening visit AND * Fractional exhaled nitric oxide \>=35 parts per billion (ppb) at screening. OR * Documented current Chronic Rhinosinusitis with Nasal Polyps.
Exclusion criteria
* Participants have had 3 or more exacerbations in the last year prior to Visit 1. * Participants on maintenance OCS or high dose ICS/LABA for asthma. * Participants with a duration of asthma greater than (\>)20 years. * 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 a history of lung cancer. Participants with current diagnoses of emphysema or chronic bronchitis (Chronic Obstructive Pulmonary Disease other than asthma) are excluded. * Participants with other conditions that could lead to elevated EOS such as hypereosinophilic syndromes including (but not limited to) Eosinophilic Granulomatosis with Polyangiitis (formerly known as Churg-Strauss Syndrome) or eosinophilic esophagitis. * Participants who developed an exacerbation within 4 weeks before screening. * Participants with a known, pre-existing parasitic infestation within 6 months prior to screening unless treated and evidenced to have been resolved. * A known immunodeficiency (e.g. human immunodeficiency virus), other than that explained by the use of CS taken as therapy for asthma. * A current malignancy or previous history of cancer in remission for less than 12 months prior to screening. * Participants who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, psychiatric, renal, gastrointestinal, hepatic, hematologic or any other system abnormalities that are uncontrolled with standard treatment. * Participants with current diagnosis of vasculitis. * Participants who have received treatment with any approved or investigational biologic monoclonal antibody (mAb). * A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to the first dose of study intervention. * Current smokers or former smokers with a smoking history of \>=20 pack years (number of pack years = \[number of cigarettes per day/20\] \* number of years smoked) and vapers. * Participants with allergy/intolerance to a mAb or biologic or any of the excipients of depemokimab. * Participants who are pregnant or breastfeeding. * Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations. * Evidence of clinically significant abnormality in the hematological, biochemical or urinalysis screen at screening (Visit 0), as judged by the investigator. Liver safety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized rate of clinically significant exacerbations | Up to Week 156 | A clinically significant exacerbation is defined as a worsening of asthma requiring the use of systemic corticosteroids. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with clinical remission at 2 years | At 2 years | Clinical remission defined as no clinically significant asthma exacerbations during the first 2 years of the treatment period, and no maintenance oral corticosteroids (OCS) for asthma at 2 years, and well controlled asthma based on an Asthma Control Test (ACT) greater than or equal to (\>=) 20 at 2 years, and no deterioration of lung function. |
| Change from Baseline in Asthma Quality of Life Questionnaire (AQLQ) total overall score at 2 years | Baseline and at 2 years | The AQLQ is a 32-item self-administered questionnaire designed to measure the impact of asthma on an individuals daily life over the last 2 weeks across four domains: Symptoms, Activity Limitations, Emotional Function, and Environmental Stimuli. Each item is scored on a 7 point scale (1 = severe impairment; 7 = no impairment). The overall score is the mean of all 32 items and ranges from 1.0 (worst quality of life) to 7.0 (best quality of life). Higher scores indicate better quality of life (QoL), with lower impairment on daily functioning and well-being. |
| Change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score at 2 years | Baseline and at 2 years | The ACQ-5 is a five-item questionnaire developed as a measure of participants asthma symptom control. The questions are designed to be self-completed by the participant. The 5 questions enquire about the frequency and/or severity of symptoms (nocturnal awakening, waking in the morning, activity limitation, shortness of breath, and wheeze) over the previous week. The overall ACQ-5 response option is the mean score of all 5 questions representing 0 with no impairment/limitation and 6 as total impairment/ limitation. Higher scores indicated more limitations and lower score with better asthma control. |
| Change from Baseline in post-Bronchodilator Forced expiratory volume in 1 second (FEV1) at 2 years | Baseline and at 2 years | 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 testing. |
| Change from Baseline in pre-Bronchodilator FEV1 at 2 years | Baseline and at 2 years | 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 testing. |
Countries
United Kingdom, United States
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Outcome results
None listed