GB001 in Adult Subjects With Moderate to Severe Asthma

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled, dose-ranging, multi-center study to evaluate the efficacy and safety of GB001 when added to standard-of care (SOC) asthma maintenance therapy in adults with moderate to severe asthma and an eosinophilic phenotype with respect to asthma worsening at the end of 24 weeks of treatment.

Official Title
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A Phase 2b, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Multi-center Study to Evaluate the Efficacy and Safety of GB001 as Maintenance Therapy in Adult Subjects With Moderate to Severe Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: GB001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria A diagnosis of asthma by a physician at least 12 months before Screening Visit. Treated with medium or high dose inhaled corticosteroid (ICS) plus additional controller for at least 12 months prior to Screening Visit. Subjects must maintain a stable ICS dose regimen during the 4 weeks prior to the Screening Visit. Forced Expiratory Volume in 1 second (FEV1) of ≤ 85% of predicted normal Demonstrated reversibility of at least 12% in FEV1 Evidence of uncontrolled asthma Eosinophilic asthma No changes in ICS dose and compliant with standard of care asthma therapy during run-in period. Exclusion Criteria Current smokers (any substance) Serious co-morbidities Fridericia's correction QT factor (QTcF) ≥450 msec (male) or ≥470 msec (female) Use of other investigational drugs within 30 days, or within 5 half-lives, whichever is longer, prior to Screening Visit Regular use of systemic corticosteroids or immunosuppressive treatments or monoclonal antibodies for asthma Pregnant or breastfeeding Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo once per day (QD) for 24 weeks | Drug: Placebo<br>* film-coated oral tablet<br>|
| Experimental: GB001 20 mg<br>GB001 20 mg QD for 24 weeks | Drug: GB001<br>* film-coated oral tablet<br>|
| Experimental: GB001 40 mg<br>GB001 40 mg QD for 24 weeks | Drug: GB001<br>* film-coated oral tablet<br>|
| Experimental: GB001 60 mg<br>GB001 60 mg QD for 24 weeks | Drug: GB001<br>* film-coated oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Who Experience Worsening of Asthma by Week 24 | Proportion of participants who experience worsening of asthma by Week 24 as defined by at least 1 of the following: On 2 consecutive days, morning (AM) peak expiratory flow (PEF) ≤ 75% of mean AM PEF measured over the last 7 days of the Run-in Forced expiratory volume in 1 second (FEV1) < 80% of baseline Increase in rescue medication use of ≥ 6 puffs/day on 2 consecutive days compared to mean use over the last 7 days of the Run-in Increase in Asthma Control Questionnaire 5 (ACQ-5; see Outcome Measure 2 for description) score of ≥ 0.5 compared to baseline The occurrence of a severe asthma exacerbation (asthma attack) defined as deterioration of asthma that leads to the use of systemic corticosteroids for at least 3 days, hospitalization, or an Emergency Department visit. | up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 24 in Asthma Control Questionnaire - 5 (ACQ-5) Score | The ACQ-5 is a 5-item questionnaire which has been developed as a measure of the participant's asthma control that can be quickly and easily completed. The questions are designed to be self-completed by the participant. The 5 questions enquire about the frequency and/or severity of symptoms in the prior week (nocturnal awakening, activity limitation, shortness of breath, wheeze). The response options for each of these questions consists of a zero (no impairment/limitation) to 6 (total impairment/limitation) scale. | Baseline, Week 24 | 
| Change From Baseline to Week 24 in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Pre-albuterol/salbutamol morning FEV1 was measured using electronic spirometry. | Baseline, Week 24 | 
| Time to First Asthma Worsening | Time to first asthma worsening is defined as the time from the date of the first dose of study treatment to the first date that any of the components of asthma worsening endpoint is met. See Outcome Measure 1 for the definition of asthma worsening. | up to Week 24 | 
| Annualized Rate of Severe Asthma Exacerbations | A severe asthma exacerbation is defined as deterioration of asthma that leads to the use of systemic corticosteroids for at least 3 days, hospitalization, or an Emergency Department visit. | up to Week 24 | 
| Change From Baseline to Week 24 in Post-Bronchodilator FEV1 | Post-albuterol/salbutamol morning FEV1 was measured using electronic spirometry. | Baseline, Week 24 | 
| Change From Baseline to Week 24 in Morning Peak Expiratory Flow (AM PEF) | AM PEF was measured by participants using an electronic diary. | Baseline, Week 24 | 
| Percentage of Participants With a Treatment-Emergent Adverse Event (AE) | An adverse event (AE) is any untoward medical occurrence in a participant, whether or not considered related to study treatment. Abnormal laboratory test results or other safety assessments, including those that worsened from baseline, that were considered clinically significant in the medical and scientific judgment of the investigator were to be reported as AEs. | From first dose of study treatment through Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GB001, eosinophilic asthma, moderate asthma, severe asthma