GB001 in Adult Participants With Chronic Rhinosinusitis

Study Overview
=================
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).

Official Title
-----------------
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Effect of GB001 in Patients With Chronic Rhinosinusitis With or Without Nasal Polyps

Conditions
-----------------
Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP), Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)

Intervention / Treatment
-----------------
* Drug: GB001
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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/exclusion criteria will apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GB001<br>GB001 40 mg once per day (QD) for 16 weeks | Drug: GB001<br>* film-coated oral tablet<br>|
| Placebo Comparator: Placebo<br>Placebo QD for 16 weeks | Drug: Placebo<br>* film-coated oral tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 16 | 
| 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. | Baseline, Week 16 | 
| 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. | up to Week 16 | 
| 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). | Baseline, Week 16 | 
| 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). | Baseline, Week 16 | 
| 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. | Baseline, Week 16 | 
| 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. | up to Week 16 | 
| 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. | From first dose of study drug through Week 20 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GB001, Gossamer Bio, Gossamer, Nasal Polyposis, CRSwNP, CRSsNP