A Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04718103

Collaborator

Iqvia Pty Ltd (Industry)

375

Enrollment

100

Locations

Arms

34.5

Anticipated Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will assess the efficacy and safety of GSK3511294 (Depemokimab) as an adjunctive therapy in participants with severe uncontrolled asthma with an eosinophilic phenotype.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Biological: GSK3511294 (Depemokimab) Biological: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

375 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomized in a 2:1 ratio to receive either GSK3511294 (Depemokimab) or placebo as an adjunct therapy.Participants will be randomized in a 2:1 ratio to receive either GSK3511294 (Depemokimab) or placebo as an adjunct therapy.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A 52-week, Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre Study of the Efficacy and Safety of GSK3511294 Adjunctive Therapy in Adult and Adolescent Participants With Severe Uncontrolled Asthma With an Eosinophilic Phenotype

Actual Study Start Date :

Feb 4, 2021

Anticipated Primary Completion Date :

Dec 22, 2023

Anticipated Study Completion Date :

Dec 22, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants receiving GSK3511294 (Depemokimab)	Biological: GSK3511294 (Depemokimab) GSK3511294 (Depemokimab) will be administered using a pre-filled syringe.
Placebo Comparator: Participants receiving Placebo	Biological: Placebo Placebo will be administered as normal saline using a pre-filled syringe.

Arm

Intervention/Treatment

Experimental: Participants receiving GSK3511294 (Depemokimab)

Biological: GSK3511294 (Depemokimab)

GSK3511294 (Depemokimab) will be administered using a pre-filled syringe.

Placebo Comparator: Participants receiving Placebo

Biological: Placebo

Placebo will be administered as normal saline using a pre-filled syringe.

Outcome Measures

Primary Outcome Measures

Annualized rate of clinically significant exacerbations over 52 weeks [Up to Week 52]

Secondary Outcome Measures

Change from Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) total score at Week 52 [Baseline (Day 1) and at Week 52]
The SGRQ is a well-established instrument, comprising 50 items designed to measure Quality of Life in participants with diseases of airway obstruction. It consists of two parts: Part 1 produces the symptom score and Part 2 produces the activity and impact score. A Total score is also calculated which summarizes the impact of the disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and zero indicates best possible health status. Higher scores indicate worse quality of life.
Change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score at Week 52 [Baseline (Day 1) and at Week 52]
The ACQ-5 is a five-item questionnaire, which has been developed as a measure of participants' asthma control that can be quickly and easily completed. The five questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, and shortness of breath, wheeze) over the previous week. The response options for all these questions consist of a zero (no impairment/limitation) to six (total impairment/ limitation) scale. Higher score indicates more limitations.
Change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at Week 52 [Baseline (Day 1) and at Week 52]
FEV1 will be measured using spirometry.
Annualized rate of exacerbations requiring hospitalization and/or Emergency Department (ED) visit over 52 weeks [Up to Week 52]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key inclusion criteria for study:

Adults and adolescents greater than or equal to (>=)12 years of age, at the time of signing the informed consent/assent.
Participants must have a documented physician diagnosis of asthma for >=2 years that meets the National Heart, Lung, and Blood Institute guidelines (NHLBI) or Global Initiative for Asthma (GINA) guidelines and

Eosinophilic phenotype: participants who have, or with high likelihood of having, asthma with an eosinophilic phenotype as per randomization criteria, and
Exacerbation history: participants who have previously confirmed history of >=2 exacerbations requiring treatment with systemic corticosteroid (CS) (Intramuscular [IM], Intravenous [IV], or oral), in the 12 months prior to Visit 1, despite the use of medium to high-dose ICS. For participants receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold dose increase or greater.

Persistent airflow obstruction as indicated by (i) For participants >=18 years of age at Visit 1, a pre-bronchodilator FEV1 less than (<)80 percent (%) predicted National Health and Nutrition Examination Survey (NHANES III) recorded at Visit 1.

(ii) For participants 12-17 years of age at Visit 1: A pre-bronchodilator FEV1 <90% predicted (NHANES III) recorded at Visit 1 or FEV1: Forced Vital Capacity (FVC) ratio <0.8 recorded at Visit 1.

A well-documented requirement for regular treatment with medium to high dose ICS (in the 12 months prior to Visit 1 with or without maintenance OCS). The maintenance ICS dose must be >=440 micrograms fluticasone propionate (FP) hydrofluoroalkane product (HFA) daily, or clinically comparable (GINA, 2020). Participants who are treated with medium dose ICS will also need to be treated with LABA to qualify for inclusion.
Current treatment with at least one additional controller medication, besides ICS, for at least 3 months (for example [e.g.], LABA, LAMA, leukotriene receptor antagonist [LTRA], or theophylline).

Key inclusion criteria for randomization:

An elevated peripheral blood eosinophil count of >=300 cells per microliter demonstrated in the past 12 months prior to Visit 1 that is related to asthma or an elevated peripheral blood eosinophil count of >=150 cells per microliter at Screening Visit 1 that is related to asthma.
Evidence of airway reversibility or responsiveness as documented by either:

(i) Airway reversibility (FEV1>=12% and 200 milliliter [mL]) demonstrated at Visit 1 or Visit 2 using the Maximum Post Bronchodilator Procedure or (ii) Airway reversibility (FEV1>=12% and 200 mL) documented in the 24 months prior to Visit 2 (randomization visit) or (iii) Airway hyper-responsiveness (methacholine: Provocative concentration causing a 20% fall in FEV1 [PC20] of <8 milligrams per milliliter (mg/mL), histamine: Provocative dose that decreases FEV1 by 20% [PD20] of <7.8 micromoles, mannitol: decrease in FEV1 as per the labelled product instructions) documented in the 24 months prior to Visit 2 (randomization visit).

Key exclusion criteria for study:

Presence of a known pre-existing, clinically important lung condition other than asthma. This includes (but is not limited to) current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
Participants with other conditions that could lead to elevated eosinophils such as hyper-eosinophilic syndromes including (but not limited to) Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly known as Churg-Strauss Syndrome) or Eosinophilic Esophagitis.
A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Participants that had localized carcinoma of the skin which was resected for cure will not be excluded).
Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.
Participants who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment.
Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis must be excluded prior to enrolment.
Participants who have received mepolizumab (Nucala), reslizumab (Cinqair/Cinqaero), or benralizumab (Fasenra) within 12 months prior to Visit 1 or who have a previous documented failure with Anti-Interleukin-5/Anti-Interleukin-5 receptor (anti-IL-5/5R) therapy.
Participants who have received omalizumab (Xolair) or dupilumab (Dupixent) within 130 days prior to Visit 1.
Participants who have received any monoclonal antibody (mAb) within 5 half-lives of Visit 1.
Previously participated in any study with mepolizumab, reslizumab, or benralizumab and received study intervention (including placebo) within 12 months prior to Visit 1.
Corrected QT interval using Fridericia's formula (QTcF) >=450 milliseconds (msec) or QTcF >=480 msec for participants with Bundle Branch Block at screening Visit 1.
Current smokers or former smokers with a smoking history of >=10 pack years (number of pack years = [number of cigarettes per day/ 20] multiplied by number of years smoked). A former smoker is defined as a participant who quit smoking at least 6 months prior to Visit 1.
Participants with allergy/intolerance to the excipients of GSK3511294 or any mAb or biologic.

Key exclusion criteria for randomization:

QTcF >= 450 msec or QTcF >=480 msec for participants with Bundle Branch Block, at randomization Visit 2 are excluded. Participants are excluded if an abnormal Electrocardiogram (ECG) finding from the 12-lead ECG conducted at Screening Visit 1 is considered to be clinically significant and would impact the participant's participation during the study, based on the evaluation of the Investigator.
Participants with a clinically significant asthma exacerbation in the 7 days prior to randomization should have their randomization visit delayed until the investigator considers the participant's asthma to be stable.
Any changes in the dose or regimen of Baseline ICS and/or additional controller medication (except for treatment of an exacerbation) during the run-in period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Alabaster	Alabama	United States	35007
2	GSK Investigational Site	Phoenix	Arizona	United States	85032
3	GSK Investigational Site	Little Rock	Arkansas	United States	72209
4	GSK Investigational Site	Lancaster	California	United States	93534
5	GSK Investigational Site	Lafayette	Colorado	United States	80026
6	GSK Investigational Site	Hialeah	Florida	United States	33016
7	GSK Investigational Site	Miami Lakes	Florida	United States	33014
8	GSK Investigational Site	Miami	Florida	United States	33144
9	GSK Investigational Site	Miami	Florida	United States	33186
10	GSK Investigational Site	Orlando	Florida	United States	32803
11	GSK Investigational Site	Lawrenceville	Georgia	United States	30046
12	GSK Investigational Site	Stockbridge	Georgia	United States	30281
13	GSK Investigational Site	Sugar Hill	Georgia	United States	30518
14	GSK Investigational Site	Columbia	Maryland	United States	21044
15	GSK Investigational Site	Ypsilanti	Michigan	United States	48197
16	GSK Investigational Site	Saint Louis	Missouri	United States	63110
17	GSK Investigational Site	Saint Louis	Missouri	United States	63141
18	GSK Investigational Site	Northfield	New Jersey	United States	08225
19	GSK Investigational Site	Toms River	New Jersey	United States	08755
20	GSK Investigational Site	New Windsor	New York	United States	12553
21	GSK Investigational Site	Huntersville	North Carolina	United States	28078
22	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
23	GSK Investigational Site	Cincinnati	Ohio	United States	45229
24	GSK Investigational Site	Edmond	Oklahoma	United States	73034
25	GSK Investigational Site	Altoona	Pennsylvania	United States	16601
26	GSK Investigational Site	DuBois	Pennsylvania	United States	15801
27	GSK Investigational Site	Rock Hill	South Carolina	United States	29732
28	GSK Investigational Site	Rapid City	South Dakota	United States	57702
29	GSK Investigational Site	Hendersonville	Tennessee	United States	37075
30	GSK Investigational Site	Baytown	Texas	United States	77521
31	GSK Investigational Site	Dallas	Texas	United States	75225
32	GSK Investigational Site	Houston	Texas	United States	77084
33	GSK Investigational Site	McKinney	Texas	United States	75069
34	GSK Investigational Site	Pharr	Texas	United States	78577
35	GSK Investigational Site	San Antonio	Texas	United States	78229
36	GSK Investigational Site	San Antonio	Texas	United States	78258
37	GSK Investigational Site	Bellingham	Washington	United States	98225
38	GSK Investigational Site	Everett	Washington	United States	98208
39	GSK Investigational Site	Quebec		Canada	G1V 4W2
40	GSK Investigational Site	Broumov		Czechia	550 01
41	GSK Investigational Site	Praha 4		Czechia	140 59
42	GSK Investigational Site	Tabor		Czechia	390 02
43	GSK Investigational Site	Teplice		Czechia	415 01
44	GSK Investigational Site	Annecy Cedex		France	74011
45	GSK Investigational Site	Caen		France	14033
46	GSK Investigational Site	Cannes Cedex		France	06414
47	GSK Investigational Site	Marseille		France	13015
48	GSK Investigational Site	Mont de Marsan		France	40024
49	GSK Investigational Site	Paris		France	75014
50	GSK Investigational Site	Strasbourg cedex		France	67091
51	GSK Investigational Site	Tours cedex 9		France	37044
52	GSK Investigational Site	Salerno	Campania	Italy	84131
53	GSK Investigational Site	Brescia	Lombardia	Italy	25123
54	GSK Investigational Site	Varese	Lombardia	Italy	21100
55	GSK Investigational Site	Foggia	Puglia	Italy	71122
56	GSK Investigational Site	Monserrato	Sardegna	Italy	09042
57	GSK Investigational Site	Palermo	Sicilia	Italy	90127
58	GSK Investigational Site	Siena	Toscana	Italy	53100
59	GSK Investigational Site	Aichi		Japan	489-8642
60	GSK Investigational Site	Chiba		Japan	275-8580
61	GSK Investigational Site	Ehime		Japan	790-0024
62	GSK Investigational Site	Fukui		Japan	910-8526
63	GSK Investigational Site	Fukuoka		Japan	802-0052
64	GSK Investigational Site	Fukuoka		Japan	805-8508
65	GSK Investigational Site	Fukushima		Japan	960-1295
66	GSK Investigational Site	Hiroshima		Japan	734-8530
67	GSK Investigational Site	Hokkaido		Japan	053-8506
68	GSK Investigational Site	Hokkaido		Japan	064-0804
69	GSK Investigational Site	Hyogo		Japan	653-0013
70	GSK Investigational Site	Hyogo		Japan	670-0849
71	GSK Investigational Site	Kagawa		Japan	761-8073
72	GSK Investigational Site	Kagawa		Japan	762-8550
73	GSK Investigational Site	Kagoshima		Japan	890-8520
74	GSK Investigational Site	Kanagawa		Japan	231-8682
75	GSK Investigational Site	Kanagawa		Japan	232-0024
76	GSK Investigational Site	Kanagawa		Japan	236-0051
77	GSK Investigational Site	Miyagi		Japan	981-8563
78	GSK Investigational Site	Niigata		Japan	951-8520
79	GSK Investigational Site	Okayama		Japan	702-8055
80	GSK Investigational Site	Osaka		Japan	596-8501
81	GSK Investigational Site	Saga		Japan	843-0393
82	GSK Investigational Site	Shizuoka		Japan	420-8527
83	GSK Investigational Site	Tokyo		Japan	103-0027
84	GSK Investigational Site	Tokyo		Japan	141-8625
85	GSK Investigational Site	Tokyo		Japan	142-8666
86	GSK Investigational Site	Tokyo		Japan	158-0097
87	GSK Investigational Site	Tokyo		Japan	185-0014
88	GSK Investigational Site	Tokyo		Japan	204-8585
89	GSK Investigational Site	Krakow		Poland	31-624
90	GSK Investigational Site	Ksawerów		Poland	95-054
91	GSK Investigational Site	Ostrowiec Swietokrzyski		Poland	27-400
92	GSK Investigational Site	Rzeszow		Poland	35-051
93	GSK Investigational Site	Pozuelo De Alarcón	Madrid	Spain	28223
94	GSK Investigational Site	Badalona		Spain	08916
95	GSK Investigational Site	Barcelona		Spain	08023
96	GSK Investigational Site	Cáceres		Spain	10003
97	GSK Investigational Site	Jerez de la Frontera		Spain	11407
98	GSK Investigational Site	Málaga		Spain	29010
99	GSK Investigational Site	Santiago de Compostela		Spain	15706
100	GSK Investigational Site	Valencia		Spain	46010