NCT03207243

Efficacy and Safety Study of GSK3772847 in Subjects With Moderately Severe Asthma

Completed Phase 2 Results posted Last updated 2 March 2020

What this trial tests

Phase 2 trial testing GSK3772847 in Asthma in 165 participants. Completed in 15 May 2019.

Timeline

14 September 2017

Primary endpoint
15 February 2019

15 May 2019

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	165
Start date	14 September 2017
Primary completion	15 February 2019
Estimated completion	15 May 2019
Sites	64 locations across Russia, Ukraine, Mexico, Canada, Australia, United States

Drugs / interventions tested

• GSK3772847 — full drug profile →
• Placebo
• Fluticasone propionate/salmeterol
• Fluticasone propionate (FLUTICASONE PROPIONATE) — full drug profile →

Conditions studied

• Asthma — all drugs for Asthma →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Asthma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Loss of Asthma Control Over Weeks 0-16 Primary · Up to Week 16

Loss of asthma control is defined as: Asthma Control Questionnaire (ACQ-5) score increase from Baseline \>=0.5 point or pre-bronchodilator forced expiratory volume in 1 second (FEV1) decrease from baseline \>7.5 % or inability to titrate inhaled corticosteroid or a clinically significant asthma exacerbation (requiring oral corticosteroid \[OCS\] and/or hospitalization). The analysis shown is for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment. Baseline is defined as Day1. Percentage

Group	Value	95% CI
Placebo	81
GSK3772847	67

Percentage of Participants With >=0.5 Point Asthma Control Questionnaire (ACQ-5) Score Increase From Baseline Secondary · Baseline and up to Week 16

The ACQ-5 is a five-item, self-completed questionnaire, which measures asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. ACQ-5 score ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicate lower asthma control. Baseline is the latest available a

Group	Value	95% CI
Placebo	39
GSK3772847	30

Percentage of Participants Who Have Pre-bronchodilator FEV1 Decrease From Baseline >7.5 % Secondary · Baseline and up to Week 16

Pulmonary function is measured by FEV1. FEV1 is the amount of air expired in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. Baseline is defined as the latest available pre-dose assessment (Day 1). Decrease from Baseline \>7.5 % in score suggests worsening of condition.

Group	Value	95% CI
Placebo	63
GSK3772847	68

Percentage of Participants With Inability to Titrate Inhaled Corticosteroids (ICS) Secondary · Up to Week 16

Corticosteroid titration allows overall clinical evaluation of the participant's asthma status taking into account both lung function and symptom control. Inability to titrate inhaled corticosteroids indicates loss of asthma control.

Group	Value	95% CI
Placebo	23
GSK3772847	30

Percentage of Participants With Clinically Significant Asthma Exacerbation Secondary · Up to Week 16

A clinically significant asthma exacerbation is defined as one requiring oral corticosteroid and/or hospitalization.

Group	Value	95% CI
Placebo	7
GSK3772847	13

Percentage of Participants With Loss of Asthma Control Over Weeks 0-6 Secondary · Up to Week 6

Loss of asthma control is defined as: ACQ-5 score increase from Baseline \>=0.5 point or pre-bronchodilator FEV1 decrease from Baseline \>7.5 % or inability to titrate inhaled corticosteroid or a clinically significant asthma exacerbation (requiring oral OCS and/or hospitalization). The analysis shown is for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment. Baseline is defined as Day1. Percentage of participants experiencing loss of asthma control up to Week 6 has been presented.

Group	Value	95% CI
Placebo	50
GSK3772847	36

Time to Loss of Asthma Control Secondary · Up to Week 16

Time to loss of asthma control was analyzed using Kaplan-Meier analysis. In this analysis, participants were either be counted as an event or they were censored. An event is defined as participants who experience loss of asthma control during the study. Censoring is defined as participants who discontinued investigational product for reasons other than loss of asthma control. The analysis shown is for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment. Participants who didn't experience

Group	Value	95% CI
Placebo	50	29 – NA
GSK3772847	96	31 – NA

Percentage of Participants With Clinically Significant Asthma Exacerbation or Inability to Titrate Secondary · Up to Week 16

A clinically significant asthma exacerbation is defined as one requiring oral corticosteroid and/or hospitalization. Participants with clinically significant asthma exacerbation or inability to titrate FP indicated loss of asthma control.

Group	Value	95% CI
Placebo	25
GSK3772847	40

Number of Participants Experiencing Asthma Related Hospitalization During the Study Period Secondary · Up to Week 16

Hospitalization is defined as an inpatient stay or least an overnight stay at the hospital or emergency ward for observation or other equivalent facility. Data has been presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

Group	Value	95% CI
Placebo	1
GSK3772847	0

Rate Per 1000 Person-years of Participants With Hospitalization Secondary · Up to Week 16

An event is defined as an on-treatment asthma-related hospitalization or emergency room visit and participants can contribute to more than one event. Rate is calculated as number of events \* 1000 divided by (number of participants in treatment group \* mean treatment exposure in years). Data has been presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

Group	Value	95% CI
Placebo	70.5
GSK3772847	0

Number of Hospitalizations or Emergency Room Visits Per Participants Secondary · Up to Week 16

The number of hospitalization or emergency room visit made by per participant due to loss of asthma control have been presented in category titles. Data has been presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

0

Group	Value	95% CI
Placebo	77
GSK3772847	78

1

Group	Value	95% CI
Placebo	1
GSK3772847	0

2

Group	Value	95% CI
Placebo	0
GSK3772847	0

>=3

Group	Value	95% CI
Placebo	0
GSK3772847	0

Change From Baseline in Asthma Control Questionnaire (ACQ-5) Total Score Secondary · Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 16

ACQ-5 is a five-item, self-completed questionnaire, which measures asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath \& wheeze) enquire about the frequency \&/or severity of symptoms over the previous week. The response options range from zero (no impairment/limitation) to six (total impairment/limitation) scale. ACQ-5 score ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicate lower asthma control. Baseline is the latest available assessment prior to first dose (

Week1; n=72, 73

Group	Value	95% CI
Placebo	-0.36	± 0.713
GSK3772847	-0.48	± 0.685

Week2; n=67, 68

Group	Value	95% CI
Placebo	-0.53	± 0.666
GSK3772847	-0.74	± 0.732

Week3; n=61, 61

Group	Value	95% CI
Placebo	-0.59	± 0.722
GSK3772847	-0.78	± 0.663

Week4; n=54, 59

Group	Value	95% CI
Placebo	-0.69	± 0.733
GSK3772847	-0.79	± 0.695

Week5; n= 42, 52

Group	Value	95% CI
Placebo	-0.80	± 0.839
GSK3772847	-0.78	± 0.804

Week6; n=40, 48

Group	Value	95% CI
Placebo	-0.80	± 0.907
GSK3772847	-0.93	± 0.692

Week7; n=34, 46

Group	Value	95% CI
Placebo	-0.92	± 0.710
GSK3772847	-0.93	± 0.785

Week8; n=33, 44

Group	Value	95% CI
Placebo	-0.95	± 0.769
GSK3772847	-1.00	± 0.755

Adverse events — posted to ClinicalTrials.gov

Time frame: SAEs and non-SAEs were collected for 16 weeks.. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 1/82 (1%)

Deaths: 0/82

GSK3772847

Serious: 2/83 (2%)

Deaths: 0/83

Serious adverse events (3 terms)

Reaction	System	Placebo	GSK3772847
Anaphylactic shock	Immune system disorders	—	—
Pneumonia	Infections and infestations	—	—
Angioedema	Skin and subcutaneous tissue disorders	—	—

Other adverse events (7 terms — click to expand)

Reaction	System	Placebo	GSK3772847
Headache	Nervous system disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Influenza	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Ventricular tachycardia	Cardiac disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: Anaphylactic shock, Pneumonia, Angioedema.

Data from ClinicalTrials.gov NCT03207243 adverse events section.

Sponsor's own description

GSK3772847, an anti-interleukin (IL)33 receptor monoclonal antibody, is a novel treatment for asthma. This is a phase 2a study which aims to evaluate efficacy, safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of GSK3772847 in subjects with moderately severe asthma. The study will be conducted in 4 phases including screening, run-in phase, treatment phase and follow-up. In treatment phase, eligible subjects will be randomized to receive either GSK3772847 or placebo administered via intravenous (IV) route every 4 weeks in addition to open-label background therapy of fluticasone propionate/ salmeterol (FP/Sal) 500/50 micrograms (mcg) twice daily. During the treatment phase, the background therapy will be switched to FP 500 mcg for 2 weeks and the dose of FP will be reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation. The total duration of study will be approximately 33 weeks and approximately 165 subjects with moderately severe asthma who are maintained on high-dose of inhaled corticosteroids/ Long-Acting Beta-2-Agonists (ICS/LABA) will be randomized.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Role of Biologics in Asthma.
   McGregor MC, Krings JG, Nair P, Castro M. · · 2019 · cited 319× · PMID 30525902 · DOI 10.1164/rccm.201810-1944ci
2. Anti-alarmins in asthma: targeting the airway epithelium with next-generation biologics.
   Porsbjerg CM, Sverrild A, Lloyd CM, Menzies-Gow AN, et al · · 2020 · cited 113× · PMID 32586879 · DOI 10.1183/13993003.00260-2020
3. IL-33 Mediated Inflammation in Chronic Respiratory Diseases-Understanding the Role of the Member of IL-1 Superfamily.
   Gabryelska A, Kuna P, Antczak A, Białasiewicz P, et al · · 2019 · cited 94× · PMID 31057533 · DOI 10.3389/fimmu.2019.00692
4. Sounding the alarmins-The role of alarmin cytokines in asthma.
   Gauvreau GM, Bergeron C, Boulet LP, Cockcroft DW, et al · · 2023 · cited 88× · PMID 36463491 · DOI 10.1111/all.15609
5. Lessons from ten years of genome-wide association studies of asthma.
   Vicente CT, Revez JA, Ferreira MAR. · · 2017 · cited 87× · PMID 29333270 · DOI 10.1038/cti.2017.54
6. Biologics in Asthma: A Molecular Perspective to Precision Medicine.
   Salter B, Lacy P, Mukherjee M. · · 2021 · cited 41× · PMID 35126131 · DOI 10.3389/fphar.2021.793409
7. IL33 and Mast Cells-The Key Regulators of Immune Responses in Gastrointestinal Cancers?
   Eissmann MF, Buchert M, Ernst M. · · 2020 · cited 31× · PMID 32719677 · DOI 10.3389/fimmu.2020.01389
8. IL1RAP expression and the enrichment of IL-33 activation signatures in severe neutrophilic asthma.
   Badi YE, Salcman B, Taylor A, Rana B, et al · · 2023 · cited 29× · PMID 35986608 · DOI 10.1111/all.15487