GB001 in Adult Subjects With Moderate to Severe Asthma

• Sponsor: GB001, Inc, a wholly owned subsidiary of Gossamer Bio, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03683576
• Collaborator: (none)
• Enrollment: 481
• Locations: 117
• Arms: 4
• Actual Duration (Months): 21.9
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: GB001; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 481 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Oct 22, 2018
• Actual Primary Completion Date: Jul 23, 2020
• Actual Study Completion Date: Aug 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo once per day (QD) for 24 weeks	Drug: Placebo; film-coated oral tablet
Experimental: GB001 20 mg GB001 20 mg QD for 24 weeks	Drug: GB001; film-coated oral tablet
Experimental: GB001 40 mg GB001 40 mg QD for 24 weeks	Drug: GB001; film-coated oral tablet
Experimental: GB001 60 mg GB001 60 mg QD for 24 weeks	Drug: GB001; film-coated oral tablet

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. Change From Baseline to Week 24 in Post-Bronchodilator FEV1 [Baseline, Week 24]

   Post-albuterol/salbutamol morning FEV1 was measured using electronic spirometry.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts 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/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Center of Albama, LLC	Birmingham	Alabama	United States	35209
2	Banner University of Arizona Medical Center	Tucson	Arizona	United States	85724
3	California Allergy and Asthma Medical Group	Los Angeles	California	United States	90025
4	Southern California Institute for Respiratory Diseases, Inc.	Los Angeles	California	United States	90048
5	North Bay Clinical Trials, Inc	Napa	California	United States	94558
6	Allergy, Asthma & Sinus Consultants, Inc	Riverside	California	United States	92506
7	Integrated Research of Inland, Inc.	Riverside	California	United States	92506
8	Allergy & Asthma Medical Group and Research Center, A P.C.	San Diego	California	United States	92123
9	Allergy and Asthma Associates of Santa Clara Valley Research Center	San Jose	California	United States	95117
10	Bensch Clinical Research LLC	Stockton	California	United States	95207
11	Pulmonary Associates	Colorado Springs	Colorado	United States	80909
12	Yale New Haven Hospital	New Haven	Connecticut	United States	06519
13	Central Florida Pulmonary Group, PA	Altamonte Springs	Florida	United States	32701
14	Central Florida Pulmonary Group, PA	Orlando	Florida	United States	32803
15	Emerald Coast Research Associates	Panama City	Florida	United States	32405
16	Allergy and Asthma Diagnostic Treatment Center	Tallahassee	Florida	United States	32308
17	Clinical Research Trials of Florida, Inc.	Tampa	Florida	United States	33607
18	The Emory Clinic	Atlanta	Georgia	United States	30322
19	Atlanta Allergy & Asthma Clinic, PA,	Marietta	Georgia	United States	30060
20	Atlanta Allergy & Asthma Clinic, PA	Stockbridge	Georgia	United States	30281
21	Treasure Valley Medical Research	Boise	Idaho	United States	83706
22	Rush University Medical Center	Chicago	Illinois	United States	60612
23	Allergy & Asthma Specialists, PSC	Owensboro	Kentucky	United States	42301
24	John Hopkins Asthma and Allergy Center	Baltimore	Maryland	United States	21224
25	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
26	University of Michigan Medicine	Ann Arbor	Michigan	United States	48109
27	Clinical Research Institute, Inc.	Minneapolis	Minnesota	United States	55402
28	Washington University School of Medicine	Saint Louis	Missouri	United States	63108
29	Atlantic Research Center, LLC	Ocean City	New Jersey	United States	07712
30	American Health Research	Charlotte	North Carolina	United States	28207
31	Clinical Research of Charlotte	Charlotte	North Carolina	United States	28277
32	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27104
33	Bernstein Clinical Research Center, LLC	Cincinnati	Ohio	United States	45231
34	Cleveland Clinic	Cleveland	Ohio	United States	44195
35	Oklahoma Institute of Allergy & Asthma Clinical Research, LLC	Oklahoma City	Oklahoma	United States	73131
36	Crisor, LLC	Medford	Oregon	United States	97504
37	Allergy and Clinical Immunology Associates	Pittsburgh	Pennsylvania	United States	15241
38	Berks Schuylkill Respiratory Specialists, Ltd.	Wyomissing	Pennsylvania	United States	19610
39	AAPRI Clinical Research Institute	Warwick	Rhode Island	United States	02886
40	Clinical Research of Rock Hill	Rock Hill	South Carolina	United States	29732
41	Corsicana Medical Research, LLC	Corsicana	Texas	United States	75110
42	Western Sky Medical Research	El Paso	Texas	United States	79903
43	Baylor College of Medicine	Houston	Texas	United States	77030
44	Allergy and Asthma Research Center, PA	San Antonio	Texas	United States	78229
45	Pulmonary Research of Abingdon, LLC	Abingdon	Virginia	United States	24210
46	MultiCare Institute for Research & Innovation	Tacoma	Washington	United States	98405
47	University of Wisconsin School of Medicine and Public Health Asthma, Allergy, and Pulmonary Clinical Research	Madison	Wisconsin	United States	53792-9988
48	Ordination Dr. Robert Voves	Feldbach		Austria	8330
49	SALK University Hospital Salzburg, State Hospital Salzburg	Salzburg		Austria
50	Medical University of Vienna, Department of Internal Medicine II, Clinical Division of Pulmonolog	Vienna		Austria
51	UCL Saint-Luc - Pneumology Department	Bruxelles		Belgium
52	Pneumocare sprl	Erpent		Belgium
53	UZ Gent - Department of Respiratory Medicine	Gent		Belgium
54	CHU de Charleroi - Site André Vésale	Montigny-le-Tilleul		Belgium
55	Inspiration Research Limited	Toronto	Ontario	Canada	M5T 3A9
56	CHUM - Departement de pneumologie	Montreal	Quebec	Canada	H2X 3E4
57	Allergiste & Immunologue - Clinic/Outpatient Facility	Montreal	Quebec	Canada	H3G 1L5
58	Centre integre universitaire de sante et de services sociaux du Nord-de-I'lle-de-Montreal - Hopital du Sacre-Coeur de Montreal	Montréal		Canada
59	Dr. Jamie Del Carpio's Clinic	Montréal		Canada
60	Inspirational Research Limited	Toronto		Canada
61	C. I. C Mauricie Inc.	Trois-Rivières		Canada
62	The Lung Centre, Vancouver General Hospital	Vancouver		Canada
63	St. Anne's University Hospital Brno, Institute of Clinical Immunology and Allergology	Brno		Czechia
64	University Hospital Hradec Kralove, Institute of Clinical Immunology and Allergollogy	Hradec Kralove		Czechia
65	MediTrial s.r.o.	Jindrichuv Hradec		Czechia	37701
66	PNEUMO-KV s.r.o.	Karlovy Vary		Czechia	36017
67	Pulmonary Outpatient Clinic - Dr. Otakar Hokynar	Kralupy nad Vltavou		Czechia	27801
68	University Hospital Olomouc, Department of Allergology and Clinical Immunology	Olomouc		Czechia	779 00
69	Medicon a.s.	Praha 4		Czechia
70	Pulmonary Outpatient Clinic Rokycany s.r.o.	Rokycany		Czechia	33722
71	Outpatient Allergology and Neurology Clinic Kasmed Ltd.	Tábor		Czechia	39002
72	La Croix Rousse Hospital	Lyon		France
73	Nord G&R Laennec Hospital	Nantes		France
74	Centre Hospitalier Annecy Genevois	Pringy		France
75	NOUVEL HOPITAL CIVIL - New Civil Hospital	Strasbourg		France	67091
76	Universitatsklinikum des Saarlandes, Klinik fur Innere Medizin V	Homburg	Saarland	Germany	66421
77	RCMS Dr. Linhoff	Berlin		Germany	10717
78	Pneumologisches Studienzentrum Margrafenstrasse	Berlin		Germany	10969
79	Institut fuer Allergie - und Asthmaforschung	Berlin		Germany	12159
80	Pneumologische Praxis am Schloss	Berlin		Germany
81	IKF Pneumologie GmbH & Co. KG	Frankfurt am Main		Germany	60596
82	Pneumologicum im Suedstadtforum	Hannover		Germany	30173
83	Schmid	Koblenz		Germany	56068
84	BAG Prof. Hoheisel/Dr. A. Bonitz	Leipzig		Germany	04275
85	Pneumologische Praxis PD Dr. med.	Leipzig		Germany
86	KLB Gesundheitsforschung Luebeck GmbH	Luebeck		Germany	23552
87	Universitätsmedizin der Johannes Gutenberg-Universität Mainz - Hospital	Mainz		Germany
88	Centrum Medycyny Oddechowej Mroz sp. j.	Białystok		Poland
89	Malopolskie Centrum Alergologii	Kraków		Poland
90	Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ)	Kraków		Poland
91	Ostrowieckie Centrum Medyczne	Ostrowiec Świętokrzyski		Poland
92	SPZOZ Proszowice	Proszowice		Poland
93	Gabinet Lekarski Zenon Bukowczan	Sucha Beskidzka		Poland
94	ALL-MED - Specjalistyczna Opieka Medyczna - Medyczny Instytut Badawczy Marek Jutel	Wrocław		Poland
95	Centrum Medyczne Melita Medical	Wrocław		Poland
96	NZOZ Lekarze Specjalisci	Wrocław		Poland
97	SPZOZ Uniwersytecki Szpital Kliniczny nr 1	Łódź		Poland
98	Hospital Clinico Universitario de Santiago de Compostela	Santiago De Compostela	A Coruna	Spain	15706
99	Hospital Universitario de Bellvitge	L'Hospitalet de Llobregat	Barcelona	Spain	08907
100	Instituto de Ciencias Medicas	Alicante		Spain	03004
101	Hospital Clinic de Barcelona	Barcelona		Spain
102	Hospital Universitari Vall d'Hebron	Barcelona		Spain
103	Hospital Universitario Doctor Peset	Valencia		Spain	46017
104	Public Institution: Dnipro Clinical Association of Urgent Medical Care under Dnipro City Council	Dnipro		Ukraine	49006
105	Public Institution "City Clinical Hospital #4" under Dnipro City Council	Dnipro		Ukraine	49102
106	Ivano-Frankivsk Central City Clinical Hospital	Ivano-Frankivsk		Ukraine	76018
107	Public Non-Profit Enterprise: City Clinical Hospital #13 under Kharkiv City Council	Kharkiv		Ukraine
108	State Organization "National Institute of Phthisiology and Pulmonolgy named after F.G. Yanovsky NAMSU"	Kyiv		Ukraine	03680
109	State Organization "National Institute of Phthisiology and Pulmonolgy named after F.G. Yanovsky NAMSU"	Kyiv		Ukraine
110	Public Institution: City Clinical Hospital #6	Zaporizhia		Ukraine	69035
111	Public Non-Profit Enterprise City Hospital #1 under Zaporizhia City Council	Zaporizhia		Ukraine	69104
112	Public Enterprise "Hospital #1" under Zhytomyr City Council	Zhytomyr		Ukraine	10002
113	Birmingham Heartlands Hospital	Birmingham		United Kingdom
114	Bradford Royal Infirmary	Bradford		United Kingdom
115	Glasgow Clinical Research Facility, Glasgow Royal Infirmary	Glasgow		United Kingdom
116	Royal Liverpool University Hospital	Liverpool		United Kingdom
117	University Hospital Southampton	Southampton		United Kingdom

Sponsors and Collaborators

• GB001, Inc, a wholly owned subsidiary of Gossamer Bio, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 16, 2020
• Statistical Analysis Plan - Apr 11, 2020

More Information

Publications

None provided.

• Responsible Party: GB001, Inc, a wholly owned subsidiary of Gossamer Bio, Inc.
• ClinicalTrials.gov Identifier: NCT03683576
• Other Study ID Numbers: GB001-2001
• First Posted: Sep 25, 2018
• Last Update Posted: Sep 16, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GB001, Inc, a wholly owned subsidiary of Gossamer Bio, Inc.: GB001; eosinophilic asthma; moderate asthma; severe asthma
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Placebo	GB001 20 mg	GB001 40 mg	GB001 60 mg
Arm/Group Description	Placebo once per day (QD) for 24 weeks	GB001 20 mg QD for 24 weeks	GB001 40 mg QD for 24 weeks	GB001 60 mg QD for 24 weeks
Period Title: Overall Study
STARTED	120	120	118	122
COMPLETED	114	116	106	114
NOT COMPLETED	6	4	12	8

Baseline Characteristics

Arm/Group Title	Placebo	GB001 20 mg	GB001 40 mg	GB001 60 mg	Total
Arm/Group Description	Placebo QD for 24 weeks	GB001 20 mg QD for 24 weeks	GB001 40 mg QD for 24 weeks	GB001 60 mg QD for 24 weeks	Total of all reporting groups
Overall Participants	120	120	118	122	480
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.5 (11.91)	52.8 (11.81)	52.9 (13.32)	49.9 (14.37)	51.8 (12.92)
Sex: Female, Male (Count of Participants)
Female	76 63.3%	86 71.7%	74 62.7%	72 59%	308 64.2%
Male	44 36.7%	34 28.3%	44 37.3%	50 41%	172 35.8%
Race/Ethnicity, Customized (Count of Participants)
White	108 90%	109 90.8%	109 92.4%	112 91.8%	438 91.3%
Black or African American	6 5%	7 5.8%	8 6.8%	6 4.9%	27 5.6%
Asian	4 3.3%	3 2.5%	0 0%	1 0.8%	8 1.7%
Other, Not Specified	1 0.8%	1 0.8%	1 0.8%	3 2.5%	6 1.3%
Native Hawaiian or Other Pacific Islander	1 0.8%	0 0%	0 0%	0 0%	1 0.2%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino	107 89.2%	113 94.2%	112 94.9%	116 95.1%	448 93.3%
Hispanic or Latino	11 9.2%	2 1.7%	5 4.2%	5 4.1%	23 4.8%
Unknown or Not Reported	2 1.7%	5 4.2%	1 0.8%	1 0.8%	9 1.9%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants Who Experience Worsening of Asthma by Week 24
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized and received at least 1 dose of study treatment.

Arm/Group Title	Placebo	GB001 20 mg	GB001 40 mg	GB001 60 mg
Arm/Group Description	Placebo QD for 24 weeks	GB001 20 mg QD for 24 weeks	GB001 40 mg QD for 24 weeks	GB001 60 mg QD for 24 weeks
Measure Participants	120	120	118	122
Number (95% Confidence Interval) [proportion of participants]	0.658 0.5%	0.567 0.5%	0.568 0.5%	0.557 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 20 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1425
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.674
	Confidence Interval	(2-Sided) 95%; 0.398 to 1.142
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 20 mg vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 40 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1482
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.677
	Confidence Interval	(2-Sided) 95%; 0.399 to 1.149
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 40 mg vs. Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 60 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1086
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.651
	Confidence Interval	(2-Sided) 95%; 0.385 to 1.100
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 60 mg vs. Placebo

2. Secondary Outcome

Title	Change From Baseline to Week 24 in Asthma Control Questionnaire - 5 (ACQ-5) Score
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized and received at least 1 dose of study treatment.

Arm/Group Title	Placebo	GB001 20 mg	GB001 40 mg	GB001 60 mg
Arm/Group Description	Placebo QD for 24 weeks	GB001 20 mg QD for 24 weeks	GB001 40 mg QD for 24 weeks	GB001 60 mg QD for 24 weeks
Measure Participants	120	120	118	122
Least Squares Mean (95% Confidence Interval) [score on a scale]	-0.89	-1.04	-1.04	-1.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 20 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1647
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 20 mg vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 40 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1737
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 40 mg vs. Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 60 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0879
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 60 mg vs. Placebo

3. Secondary Outcome

Title	Change From Baseline to Week 24 in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Description	Pre-albuterol/salbutamol morning FEV1 was measured using electronic spirometry.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized and received at least 1 dose of study treatment.

Arm/Group Title	Placebo	GB001 20 mg	GB001 40 mg	GB001 60 mg
Arm/Group Description	Placebo QD for 24 weeks	GB001 20 mg QD for 24 weeks	GB001 40 mg QD for 24 weeks	GB001 60 mg QD for 24 weeks
Measure Participants	120	120	118	122
Least Squares Mean (95% Confidence Interval) [liters (L)]	0.105	0.121	0.146	0.180

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 20 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7718
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.016
	Confidence Interval	(2-Sided) 95%; -0.091 to 0.123
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 20 mg vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 40 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4562
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.041
	Confidence Interval	(2-Sided) 95%; -0.067 to 0.149
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 40 mg vs. Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 60 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1631
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.075
	Confidence Interval	(2-Sided) 95%; -0.030 to 0.180
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 60 mg vs. Placebo

4. Secondary Outcome

Title	Time to First Asthma Worsening
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized and received at least 1 dose of study treatment.

Arm/Group Title	Placebo	GB001 20 mg	GB001 40 mg	GB001 60 mg
Arm/Group Description	Placebo QD for 24 weeks	GB001 20 mg QD for 24 weeks	GB001 40 mg QD for 24 weeks	GB001 60 mg QD for 24 weeks
Measure Participants	120	120	118	122
Median (95% Confidence Interval) [weeks]	10.57	17.43	17.57	19.86

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 20 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0466
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.719
	Confidence Interval	(2-Sided) 95%; 0.519 to 0.995
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 20 mg vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 40 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1222
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.773
	Confidence Interval	(2-Sided) 95%; 0.558 to 1.071
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 40 mg vs. Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 60 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0304
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.698
	Confidence Interval	(2-Sided) 95%; 0.505 to 0.967
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 60 mg vs. Placebo

5. Secondary Outcome

Title	Annualized Rate of Severe Asthma Exacerbations
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized and received at least 1 dose of study treatment.

Arm/Group Title	Placebo	GB001 20 mg	GB001 40 mg	GB001 60 mg
Arm/Group Description	Placebo QD for 24 weeks	GB001 20 mg QD for 24 weeks	GB001 40 mg QD for 24 weeks	GB001 60 mg QD for 24 weeks
Measure Participants	120	120	118	122
Least Squares Mean (95% Confidence Interval) [events/year]	0.933	0.744	0.698	0.829

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 20 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3382
	Comments
	Method	Negative binomial regression model
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.797
	Confidence Interval	(2-Sided) 95%; 0.501 to 1.268
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 20 mg vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 40 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2248
	Comments
	Method	Negative binomial regression model
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.748
	Confidence Interval	(2-Sided) 95%; 0.469 to 1.195
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 40 mg vs. Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 60 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6090
	Comments
	Method	Negative binomial regression model
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.889
	Confidence Interval	(2-Sided) 95%; 0.565 to 1.397
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 60 mg vs. Placebo

6. Secondary Outcome

Title	Change From Baseline to Week 24 in Post-Bronchodilator FEV1
Description	Post-albuterol/salbutamol morning FEV1 was measured using electronic spirometry.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized and received at least 1 dose of study treatment.

Arm/Group Title	Placebo	GB001 20 mg	GB001 40 mg	GB001 60 mg
Arm/Group Description	Placebo QD for 24 weeks	GB001 20 mg QD for 24 weeks	GB001 40 mg QD for 24 weeks	GB001 60 mg QD for 24 weeks
Measure Participants	120	120	118	122
Least Squares Mean (95% Confidence Interval) [L]	0.012	-0.011	0.047	0.091

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 20 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6645
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.023
	Confidence Interval	(2-Sided) 95%; -0.127 to 0.081
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 20 mg vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 40 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5288
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.035
	Confidence Interval	(2-Sided) 95%; -0.074 to 0.144
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 40 mg vs. Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 60 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1362
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.079
	Confidence Interval	(2-Sided) 95%; -0.025 to 0.182
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 60 mg vs. Placebo

7. Secondary Outcome

Title	Change From Baseline to Week 24 in Morning Peak Expiratory Flow (AM PEF)
Description	AM PEF was measured by participants using an electronic diary.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized and received at least 1 dose of study treatment.

Arm/Group Title	Placebo	GB001 20 mg	GB001 40 mg	GB001 60 mg
Arm/Group Description	Placebo QD for 24 weeks	GB001 20 mg QD for 24 weeks	GB001 40 mg QD for 24 weeks	GB001 60 mg QD for 24 weeks
Measure Participants	120	120	118	122
Least Squares Mean (95% Confidence Interval) [L/min]	8.993	15.115	22.941	14.581

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 20 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3957
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	6.122
	Confidence Interval	(2-Sided) 95%; -8.007 to 20.251
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 20 mg vs. Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 40 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0598
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	13.948
	Confidence Interval	(2-Sided) 95%; -0.578 to 28.474
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 40 mg vs. Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GB001 60 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4376
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.588
	Confidence Interval	(2-Sided) 95%; -8.522 to 19.698
	Parameter Dispersion	Type: Value:
	Estimation Comments	GB001 60 mg vs. Placebo

8. Secondary Outcome

Title	Percentage of Participants With a Treatment-Emergent Adverse Event (AE)
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study treatment.

Arm/Group Title	Placebo	GB001 20 mg	GB001 40 mg	GB001 60 mg
Arm/Group Description	Placebo QD for 24 weeks	GB001 20 mg QD for 24 weeks	GB001 40 mg QD for 24 weeks	GB001 60 mg QD for 24 weeks
Measure Participants	120	120	118	122
Number [percentage of participants]	65.8 54.8%	65.8 54.8%	69.5 58.9%	68.0 55.7%

Adverse Events

Time Frame	From first dose of study treatment through Week 28
Arm/Group Title	Placebo		GB001 20 mg		GB001 40 mg		GB001 60 mg
Arm/Group Description	Placebo QD for 24 weeks		GB001 20 mg QD for 24 weeks		GB001 40 mg QD for 24 weeks		GB001 60 mg QD for 24 weeks
All Cause Mortality
	Placebo		GB001 20 mg		GB001 40 mg		GB001 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/120 (0%)		0/120 (0%)		0/118 (0%)		1/122 (0.8%)
Serious Adverse Events
	Placebo		GB001 20 mg		GB001 40 mg		GB001 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/120 (7.5%)		5/120 (4.2%)		5/118 (4.2%)		7/122 (5.7%)
Cardiac disorders
Left ventricular failure	0/120 (0%)		0/120 (0%)		1/118 (0.8%)		0/122 (0%)
Acute myocardial infarction	1/120 (0.8%)		0/120 (0%)		0/118 (0%)		0/122 (0%)
Myocardial infarction	1/120 (0.8%)		0/120 (0%)		0/118 (0%)		0/122 (0%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	0/120 (0%)		1/120 (0.8%)		0/118 (0%)		0/122 (0%)
Hepatobiliary disorders
Liver injury	0/120 (0%)		0/120 (0%)		0/118 (0%)		1/122 (0.8%)
Infections and infestations
Pneumonia	1/120 (0.8%)		0/120 (0%)		0/118 (0%)		1/122 (0.8%)
Sinusitis	0/120 (0%)		0/120 (0%)		1/118 (0.8%)		0/122 (0%)
Influenza	1/120 (0.8%)		0/120 (0%)		0/118 (0%)		0/122 (0%)
Respiratory tract infection	1/120 (0.8%)		0/120 (0%)		0/118 (0%)		0/122 (0%)
Injury, poisoning and procedural complications
Foot fracture	0/120 (0%)		0/120 (0%)		0/118 (0%)		1/122 (0.8%)
Fracture displacement	1/120 (0.8%)		0/120 (0%)		0/118 (0%)		0/122 (0%)
Metabolism and nutrition disorders
Mineral metabolism disorder	0/120 (0%)		0/120 (0%)		0/118 (0%)		1/122 (0.8%)
Musculoskeletal and connective tissue disorders
Back pain	0/120 (0%)		0/120 (0%)		1/118 (0.8%)		0/122 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myeloid leukaemia	0/120 (0%)		0/120 (0%)		0/118 (0%)		1/122 (0.8%)
Small cell lung cancer	0/120 (0%)		0/120 (0%)		0/118 (0%)		1/122 (0.8%)
Nervous system disorders
Myasthenia gravis	1/120 (0.8%)		0/120 (0%)		0/118 (0%)		0/122 (0%)
Renal and urinary disorders
Ureterolithiasis	0/120 (0%)		1/120 (0.8%)		0/118 (0%)		0/122 (0%)
Reproductive system and breast disorders
Uterine haemorrhage	0/120 (0%)		0/120 (0%)		1/118 (0.8%)		0/122 (0%)
Uterine polyp	0/120 (0%)		0/120 (0%)		1/118 (0.8%)		0/122 (0%)
Metrorrhagia	1/120 (0.8%)		0/120 (0%)		0/118 (0%)		0/122 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/120 (1.7%)		2/120 (1.7%)		2/118 (1.7%)		1/122 (0.8%)
Acute respiratory failure	0/120 (0%)		0/120 (0%)		1/118 (0.8%)		0/122 (0%)
Allergic bronchitis	0/120 (0%)		0/120 (0%)		1/118 (0.8%)		0/122 (0%)
Chronic obstructive pulmonary disease	0/120 (0%)		0/120 (0%)		1/118 (0.8%)		0/122 (0%)
Pneumothorax	0/120 (0%)		0/120 (0%)		0/118 (0%)		1/122 (0.8%)
Skin and subcutaneous tissue disorders
Angioedema	0/120 (0%)		1/120 (0.8%)		0/118 (0%)		0/122 (0%)
Vascular disorders
Hypertension	0/120 (0%)		0/120 (0%)		1/118 (0.8%)		0/122 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		GB001 20 mg		GB001 40 mg		GB001 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/120 (37.5%)		53/120 (44.2%)		59/118 (50%)		55/122 (45.1%)
Gastrointestinal disorders
Diarrhoea	3/120 (2.5%)		6/120 (5%)		1/118 (0.8%)		4/122 (3.3%)
Infections and infestations
Nasopharyngitis	19/120 (15.8%)		23/120 (19.2%)		29/118 (24.6%)		17/122 (13.9%)
Sinusitis	3/120 (2.5%)		4/120 (3.3%)		10/118 (8.5%)		3/122 (2.5%)
Upper respiratory tract infection	7/120 (5.8%)		3/120 (2.5%)		8/118 (6.8%)		4/122 (3.3%)
Rhinitis	6/120 (5%)		1/120 (0.8%)		2/118 (1.7%)		7/122 (5.7%)
Bronchitis	6/120 (5%)		4/120 (3.3%)		1/118 (0.8%)		1/122 (0.8%)
Investigations
Aspartate aminotransferase increased	2/120 (1.7%)		2/120 (1.7%)		4/118 (3.4%)		13/122 (10.7%)
Alanine aminotransferase increased	1/120 (0.8%)		2/120 (1.7%)		3/118 (2.5%)		13/122 (10.7%)
Nervous system disorders
Headache	11/120 (9.2%)		14/120 (11.7%)		14/118 (11.9%)		13/122 (10.7%)
Skin and subcutaneous tissue disorders
Pruritus	1/120 (0.8%)		1/120 (0.8%)		2/118 (1.7%)		8/122 (6.6%)
Vascular disorders
Hypertension	2/120 (1.7%)		3/120 (2.5%)		6/118 (5.1%)		5/122 (4.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.