Chronic Rhinosinusitis With Nasal Polyps (CRSwNP), Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)
Conditions
Keywords
GB001, Gossamer Bio, Gossamer, Nasal Polyposis, CRSwNP, CRSsNP
Brief summary
A Phase 2a, randomized, double-blind, placebo-controlled, multi-center study to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of GB001 compared with placebo over 16 weeks of treatment in patients with chronic rhinosinusitis with or without nasal polyposis (NP).
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 75 Years
Healthy volunteers
No
Inclusion criteria
* A diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP) or chronic rhinosinusitis without nasal polyps (CRSsNP) by a physician at least 12 weeks before Screening Visit * Treated with stable intranasal corticosteroid (INCS) for at least 2 months prior to Screening Visit * Presence of at least 2 nasal symptoms: nasal blockage/ obstruction/congestion or nasal discharge or facial pain/pressure or reduction/loss of smell * Women of childbearing potential must use an acceptable method of contraception
Exclusion criteria
* Sino-Nasal Outcome Test-22 (SNOT-22) score \< 20 at screening * Asthma or chronic obstructive pulmonary disease (COPD) patients that are current smokers * Use of other investigational drugs within 30 days, or within 5 half-lives, whichever is longer, prior to Screening Visit * Pregnant or breastfeeding * Pre-existing clinically important co-morbidities * Regular use of systemic corticosteroids or immunosuppressive treatments Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 16 in Sino-Nasal Outcome Test (SNOT) 22 Total Score | Baseline, Week 16 | The SNOT-22 is a validated questionnaire to assess the impact of chronic rhinosinusitis (CRS) on quality of life and utilizes a 2-week recall period. It is a 22-item outcome measure on a 5-point category scale applicable to sinonasal conditions and surgical treatments. The total scores range from 0 to 110 with higher total scores implying greater impact of CRS on quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 16 in Nasal Polyp Score (NPS) | Baseline, Week 16 | The bilateral endoscopic NPS is the sum of the right and left nostril scores, as evaluated by means of blinded, centrally read nasal endoscopy and ranges from 0 to 8. NP is graded based on polyp size: 0 = No polyps, 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate, 2 = Polyps reaching below the lower border of the middle turbinate, 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate, and 4 = Large polyps causing complete obstruction of the inferior nasal cavity. |
| Time to First Response in NPS | up to Week 16 | Response was defined as ≥ 1-point improvement from baseline. The bilateral endoscopic NPS is the sum of the right and left nostril scores, as evaluated by means of blinded, centrally read nasal endoscopy and ranges from 0-8. NP is graded based on polyp size: 0 = No polyps, 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate, 2 = Polyps reaching below the lower border of the middle turbinate, 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate, and 4 = Large polyps causing complete obstruction of the inferior nasal cavity. |
| Change From Baseline to Week 16 in Morning (AM) Nasal Congestion (NC) Score | Baseline, Week 16 | AM NC score was assessed using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). |
| Change From Baseline to Week 16 in Lund-Mackay Score | Baseline, Week 16 | Lund-Mackay scores are based on centralized imaging data assessments and are scored by blinded central reading at the imaging core laboratory. The Lund-Mackay system is based on localization with points given for degree of opacification: 0=normal, 1=partial opacification, 2=total opacification. These points are then applied to each sinus (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus) on each side. The osteomeatal complex on each side is graded as 0=not occluded, or 2=occluded. The maximum score is 12 per side, for a total score ranging from 0 to 24. |
| Change From Baseline to Week 16 in University of Pennsylvania Smell Identification Test (UPSIT) Score | Baseline, Week 16 | The UPSIT test consists of four booklets, each containing 10 odorants with one odorant per page. The test-time is about 15 minutes. The stimuli are embedded in 10-50 μm diameter plastic microcapsules on brown strips at the bottom of each page. Above each odorant strip is a multiple-choice question with four alternative words to describe the odor. The participant is asked to release the odorant by rubbing the brown-strip with the tip of a pencil and to indicate which of 4 words best describes the odor. An UPSIT result is scored from 0 to 40 where a higher score indicates better olfaction. |
| Time to First Chronic Rhinosinusitis (CRS) Exacerbation | up to Week 16 | Chronic rhinosinusitis exacerbation is defined as deterioration of CRS symptoms requiring treatment with an antibiotic, an anti-inflammatory drug, or a symptom reliever; an Emergency Department visit; or hospitalization. |
| Percentage of Participants With a Treatment-Emergent Adverse Event (AE) | From first dose of study drug through Week 20 | An adverse event (AE) is any untoward medical occurrence in a participant, whether or not considered related to study drug. 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 16 in AM Total Symptom Score (TSS) | Baseline, Week 16 | AM TSS is the sum of the scores from the 4 AM symptom categories (congestion and/or obstruction, anterior rhinorrhea, posterior rhinorrhea, loss of sense of smell) and ranges from 0-12. Each symptom category was assessed using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). |
Countries
Czechia, Ukraine, United States
Participant flow
Pre-assignment details
The study included a run-in period, during which eligibility for randomization was determined. 192 participants entered the run-in period, 97 of whom were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo QD for 16 weeks | 50 |
| GB001 GB001 40 mg QD for 16 weeks | 47 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | GB001 | Total |
|---|---|---|---|
| Age, Continuous | 51.6 years STANDARD_DEVIATION 10.34 | 51.7 years STANDARD_DEVIATION 11.81 | 51.7 years STANDARD_DEVIATION 11.02 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 5 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 46 Participants | 46 Participants | 92 Participants |
| Race/Ethnicity, Customized White | 47 Participants | 41 Participants | 88 Participants |
| Sex: Female, Male Female | 21 Participants | 28 Participants | 49 Participants |
| Sex: Female, Male Male | 29 Participants | 19 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 47 |
| other Total, other adverse events | 10 / 50 | 12 / 47 |
| serious Total, serious adverse events | 0 / 50 | 1 / 47 |
Outcome results
Primary
Change From Baseline to Week 16 in Sino-Nasal Outcome Test (SNOT) 22 Total Score
The SNOT-22 is a validated questionnaire to assess the impact of chronic rhinosinusitis (CRS) on quality of life and utilizes a 2-week recall period. It is a 22-item outcome measure on a 5-point category scale applicable to sinonasal conditions and surgical treatments. The total scores range from 0 to 110 with higher total scores implying greater impact of CRS on quality of life.
Time frame: Baseline, Week 16
Population: Intent-to-treat (ITT) population: all participants who were randomized and received at least 1 dose of study treatment. Participants with a baseline and a post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 16 in Sino-Nasal Outcome Test (SNOT) 22 Total Score | -18.1 score on a scale |
| GB001 | Change From Baseline to Week 16 in Sino-Nasal Outcome Test (SNOT) 22 Total Score | -18.3 score on a scale |
p-value: 0.949995% CI: [-7.6, 7.1]Mixed Models Analysis
Secondary
Change From Baseline to Week 16 in AM Total Symptom Score (TSS)
AM TSS is the sum of the scores from the 4 AM symptom categories (congestion and/or obstruction, anterior rhinorrhea, posterior rhinorrhea, loss of sense of smell) and ranges from 0-12. Each symptom category was assessed using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms).
Time frame: Baseline, Week 16
Population: ITT population: all participants who were randomized and received at least 1 dose of study treatment. Participants with a baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 16 in AM Total Symptom Score (TSS) | -2.499 score on a scale |
| GB001 | Change From Baseline to Week 16 in AM Total Symptom Score (TSS) | -1.867 score on a scale |
p-value: 0.174295% CI: [-0.28, 1.544]Mixed Models Analysis
Secondary
Change From Baseline to Week 16 in Lund-Mackay Score
Lund-Mackay scores are based on centralized imaging data assessments and are scored by blinded central reading at the imaging core laboratory. The Lund-Mackay system is based on localization with points given for degree of opacification: 0=normal, 1=partial opacification, 2=total opacification. These points are then applied to each sinus (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus) on each side. The osteomeatal complex on each side is graded as 0=not occluded, or 2=occluded. The maximum score is 12 per side, for a total score ranging from 0 to 24.
Time frame: Baseline, Week 16
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 16 in Lund-Mackay Score | -0.6 score on a scale |
| GB001 | Change From Baseline to Week 16 in Lund-Mackay Score | -0.9 score on a scale |
p-value: 0.677895% CI: [-1.8, 1.2]ANCOVA
Secondary
Change From Baseline to Week 16 in Morning (AM) Nasal Congestion (NC) Score
AM NC score was assessed using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms).
Time frame: Baseline, Week 16
Population: ITT population: all participants who were randomized and received at least 1 dose of study treatment. Participants with a baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 16 in Morning (AM) Nasal Congestion (NC) Score | -0.733 score on a scale |
| GB001 | Change From Baseline to Week 16 in Morning (AM) Nasal Congestion (NC) Score | -0.543 score on a scale |
p-value: 0.163595% CI: [-0.077, 0.459]Mixed Models Analysis
Secondary
Change From Baseline to Week 16 in Nasal Polyp Score (NPS)
The bilateral endoscopic NPS is the sum of the right and left nostril scores, as evaluated by means of blinded, centrally read nasal endoscopy and ranges from 0 to 8. NP is graded based on polyp size: 0 = No polyps, 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate, 2 = Polyps reaching below the lower border of the middle turbinate, 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate, and 4 = Large polyps causing complete obstruction of the inferior nasal cavity.
Time frame: Baseline, Week 16
Population: ITT population: all participants who were randomized and received at least 1 dose of study treatment. Participants with nasal polyps with a baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 16 in Nasal Polyp Score (NPS) | -0.8 score on a scale |
| GB001 | Change From Baseline to Week 16 in Nasal Polyp Score (NPS) | -0.7 score on a scale |
p-value: 0.791495% CI: [-0.7, 0.9]Mixed Models Analysis
Secondary
Change From Baseline to Week 16 in University of Pennsylvania Smell Identification Test (UPSIT) Score
The UPSIT test consists of four booklets, each containing 10 odorants with one odorant per page. The test-time is about 15 minutes. The stimuli are embedded in 10-50 μm diameter plastic microcapsules on brown strips at the bottom of each page. Above each odorant strip is a multiple-choice question with four alternative words to describe the odor. The participant is asked to release the odorant by rubbing the brown-strip with the tip of a pencil and to indicate which of 4 words best describes the odor. An UPSIT result is scored from 0 to 40 where a higher score indicates better olfaction.
Time frame: Baseline, Week 16
Population: ITT population: all participants who were randomized and received at least 1 dose of study treatment. Participants with a baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 16 in University of Pennsylvania Smell Identification Test (UPSIT) Score | 1.5 score on a scale |
| GB001 | Change From Baseline to Week 16 in University of Pennsylvania Smell Identification Test (UPSIT) Score | 2.3 score on a scale |
p-value: 0.485195% CI: [-1.6, 3.4]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 drug. 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 drug through Week 20
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) | 36.0 percentage of participants |
| GB001 | Percentage of Participants With a Treatment-Emergent Adverse Event (AE) | 44.7 percentage of participants |
Secondary
Time to First Chronic Rhinosinusitis (CRS) Exacerbation
Chronic rhinosinusitis exacerbation is defined as deterioration of CRS symptoms requiring treatment with an antibiotic, an anti-inflammatory drug, or a symptom reliever; an Emergency Department visit; or hospitalization.
Time frame: up to Week 16
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 Chronic Rhinosinusitis (CRS) Exacerbation | NA weeks |
| GB001 | Time to First Chronic Rhinosinusitis (CRS) Exacerbation | NA weeks |
p-value: 0.389895% CI: [0.136, 2.178]Regression, Cox
Secondary
Time to First Response in NPS
Response was defined as ≥ 1-point improvement from baseline. The bilateral endoscopic NPS is the sum of the right and left nostril scores, as evaluated by means of blinded, centrally read nasal endoscopy and ranges from 0-8. NP is graded based on polyp size: 0 = No polyps, 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate, 2 = Polyps reaching below the lower border of the middle turbinate, 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate, and 4 = Large polyps causing complete obstruction of the inferior nasal cavity.
Time frame: up to Week 16
Population: ITT population: all participants who were randomized and received at least 1 dose of study treatment. Participants with nasal polyps.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Response in NPS | 16.43 weeks |
| GB001 | Time to First Response in NPS | 16.14 weeks |
p-value: 0.891695% CI: [0.41, 2.173]Regression, Cox