Asthma
Conditions
Keywords
GB001, eosinophilic asthma, moderate asthma, severe asthma
Brief summary
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.
Interventions
DRUGGB001
film-coated oral tablet
DRUGPlacebo
film-coated oral tablet
Sponsors
GB001, Inc, a wholly owned subsidiary of Gossamer Bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Experience Worsening of Asthma by Week 24 | up to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Baseline, Week 24 | Pre-albuterol/salbutamol morning FEV1 was measured using electronic spirometry. |
| Time to First Asthma Worsening | up to Week 24 | 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. |
| Annualized Rate of Severe Asthma Exacerbations | up to Week 24 | 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. |
| Change From Baseline to Week 24 in Asthma Control Questionnaire - 5 (ACQ-5) Score | Baseline, Week 24 | 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. |
| Change From Baseline to Week 24 in Morning Peak Expiratory Flow (AM PEF) | Baseline, Week 24 | AM PEF was measured by participants using an electronic diary. |
| Percentage of Participants With a Treatment-Emergent Adverse Event (AE) | From first dose of study treatment through Week 28 | 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. |
| Change From Baseline to Week 24 in Post-Bronchodilator FEV1 | Baseline, Week 24 | Post-albuterol/salbutamol morning FEV1 was measured using electronic spirometry. |
Countries
Austria, Belgium, Canada, Czechia, France, Germany, Poland, Spain, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
The study included a run-in period, during which eligibility for randomization was determined. 731 participants entered the run-in period, 481 of whom were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo QD for 24 weeks | 120 |
| GB001 20 mg GB001 20 mg QD for 24 weeks | 120 |
| GB001 40 mg GB001 40 mg QD for 24 weeks | 118 |
| GB001 60 mg GB001 60 mg QD for 24 weeks | 122 |
| Total | 480 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 0 | 4 |
| Overall Study | Lack of Efficacy | 1 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 | 0 |
| Overall Study | Other, Not Specified | 0 | 2 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 8 | 3 |
Baseline characteristics
| Characteristic | Placebo | GB001 20 mg | GB001 40 mg | GB001 60 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 51.5 years STANDARD_DEVIATION 11.91 | 52.8 years STANDARD_DEVIATION 11.81 | 52.9 years STANDARD_DEVIATION 13.32 | 49.9 years STANDARD_DEVIATION 14.37 | 51.8 years STANDARD_DEVIATION 12.92 |
| Race/Ethnicity, Customized Asian | 4 Participants | 3 Participants | 0 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 7 Participants | 8 Participants | 6 Participants | 27 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 11 Participants | 2 Participants | 5 Participants | 5 Participants | 23 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 107 Participants | 113 Participants | 112 Participants | 116 Participants | 448 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 2 Participants | 5 Participants | 1 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 108 Participants | 109 Participants | 109 Participants | 112 Participants | 438 Participants |
| Sex: Female, Male Female | 76 Participants | 86 Participants | 74 Participants | 72 Participants | 308 Participants |
| Sex: Female, Male Male | 44 Participants | 34 Participants | 44 Participants | 50 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 120 | 0 / 120 | 0 / 118 | 1 / 122 |
| other Total, other adverse events | 45 / 120 | 53 / 120 | 59 / 118 | 55 / 122 |
| serious Total, serious adverse events | 9 / 120 | 5 / 120 | 5 / 118 | 7 / 122 |
Outcome results
Primary
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.
Time frame: up to Week 24
Population: ITT Population: all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants Who Experience Worsening of Asthma by Week 24 | 0.658 proportion of participants |
| GB001 20 mg | Proportion of Participants Who Experience Worsening of Asthma by Week 24 | 0.567 proportion of participants |
| GB001 40 mg | Proportion of Participants Who Experience Worsening of Asthma by Week 24 | 0.568 proportion of participants |
| GB001 60 mg | Proportion of Participants Who Experience Worsening of Asthma by Week 24 | 0.557 proportion of participants |
p-value: 0.142595% CI: [0.398, 1.142]Regression, Logistic
p-value: 0.148295% CI: [0.399, 1.149]Regression, Logistic
p-value: 0.108695% CI: [0.385, 1.1]Regression, Logistic
Secondary
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.
Time frame: up to Week 24
Population: ITT Population: all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Annualized Rate of Severe Asthma Exacerbations | 0.933 events/year |
| GB001 20 mg | Annualized Rate of Severe Asthma Exacerbations | 0.744 events/year |
| GB001 40 mg | Annualized Rate of Severe Asthma Exacerbations | 0.698 events/year |
| GB001 60 mg | Annualized Rate of Severe Asthma Exacerbations | 0.829 events/year |
p-value: 0.338295% CI: [0.501, 1.268]Negative binomial regression model
p-value: 0.224895% CI: [0.469, 1.195]Negative binomial regression model
p-value: 0.60995% CI: [0.565, 1.397]Negative binomial regression model
Secondary
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.
Time frame: Baseline, Week 24
Population: ITT Population: all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 24 in Asthma Control Questionnaire - 5 (ACQ-5) Score | -0.89 score on a scale |
| GB001 20 mg | Change From Baseline to Week 24 in Asthma Control Questionnaire - 5 (ACQ-5) Score | -1.04 score on a scale |
| GB001 40 mg | Change From Baseline to Week 24 in Asthma Control Questionnaire - 5 (ACQ-5) Score | -1.04 score on a scale |
| GB001 60 mg | Change From Baseline to Week 24 in Asthma Control Questionnaire - 5 (ACQ-5) Score | -1.08 score on a scale |
p-value: 0.164795% CI: [-0.36, 0.06]ANCOVA
p-value: 0.173795% CI: [-0.37, 0.07]ANCOVA
p-value: 0.087995% CI: [-0.4, 0.03]ANCOVA
Secondary
Change From Baseline to Week 24 in Morning Peak Expiratory Flow (AM PEF)
AM PEF was measured by participants using an electronic diary.
Time frame: Baseline, Week 24
Population: ITT Population: all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 24 in Morning Peak Expiratory Flow (AM PEF) | 8.993 L/min |
| GB001 20 mg | Change From Baseline to Week 24 in Morning Peak Expiratory Flow (AM PEF) | 15.115 L/min |
| GB001 40 mg | Change From Baseline to Week 24 in Morning Peak Expiratory Flow (AM PEF) | 22.941 L/min |
| GB001 60 mg | Change From Baseline to Week 24 in Morning Peak Expiratory Flow (AM PEF) | 14.581 L/min |
p-value: 0.395795% CI: [-8.007, 20.251]ANCOVA
p-value: 0.059895% CI: [-0.578, 28.474]ANCOVA
p-value: 0.437695% CI: [-8.522, 19.698]ANCOVA
Secondary
Change From Baseline to Week 24 in Post-Bronchodilator FEV1
Post-albuterol/salbutamol morning FEV1 was measured using electronic spirometry.
Time frame: Baseline, Week 24
Population: ITT Population: all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 24 in Post-Bronchodilator FEV1 | 0.012 L |
| GB001 20 mg | Change From Baseline to Week 24 in Post-Bronchodilator FEV1 | -0.011 L |
| GB001 40 mg | Change From Baseline to Week 24 in Post-Bronchodilator FEV1 | 0.047 L |
| GB001 60 mg | Change From Baseline to Week 24 in Post-Bronchodilator FEV1 | 0.091 L |
p-value: 0.664595% CI: [-0.127, 0.081]ANCOVA
p-value: 0.528895% CI: [-0.074, 0.144]ANCOVA
p-value: 0.136295% CI: [-0.025, 0.182]ANCOVA
Secondary
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.
Time frame: Baseline, Week 24
Population: ITT Population: all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 24 in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | 0.105 liters (L) |
| GB001 20 mg | Change From Baseline to Week 24 in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | 0.121 liters (L) |
| GB001 40 mg | Change From Baseline to Week 24 in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | 0.146 liters (L) |
| GB001 60 mg | Change From Baseline to Week 24 in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | 0.180 liters (L) |
p-value: 0.771895% CI: [-0.091, 0.123]ANCOVA
p-value: 0.456295% CI: [-0.067, 0.149]ANCOVA
p-value: 0.163195% CI: [-0.03, 0.18]ANCOVA
Secondary
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.
Time frame: From first dose of study treatment through Week 28
Population: Safety Population: all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Treatment-Emergent Adverse Event (AE) | 65.8 percentage of participants |
| GB001 20 mg | Percentage of Participants With a Treatment-Emergent Adverse Event (AE) | 65.8 percentage of participants |
| GB001 40 mg | Percentage of Participants With a Treatment-Emergent Adverse Event (AE) | 69.5 percentage of participants |
| GB001 60 mg | Percentage of Participants With a Treatment-Emergent Adverse Event (AE) | 68.0 percentage of participants |
Secondary
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.
Time frame: up to Week 24
Population: ITT Population: all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Asthma Worsening | 10.57 weeks |
| GB001 20 mg | Time to First Asthma Worsening | 17.43 weeks |
| GB001 40 mg | Time to First Asthma Worsening | 17.57 weeks |
| GB001 60 mg | Time to First Asthma Worsening | 19.86 weeks |
p-value: 0.046695% CI: [0.519, 0.995]Regression, Cox
p-value: 0.122295% CI: [0.558, 1.071]Regression, Cox
p-value: 0.030495% CI: [0.505, 0.967]Regression, Cox