A Safety and Efficacy Study of Mepolizumab in Subjects With Severe Asthma

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03562195

Collaborator

(none)

300

Enrollment

Locations

Arms

48.3

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Mepolizumab, a humanized monoclonal antibody, has been developed as an add-on treatment for subjects with severe asthma with eosinophilic inflammation. Current asthma treatment guidelines offer minimal options for the severe asthmatic subjects on intensive therapy with frequent exacerbations. There is a significant unmet medical need to provide better treatment options for this segment of the asthma population. Thus, this study is designed to evaluate the efficacy and safety of mepolizumab in Chinese severe asthmatic subjects with eosinophilic inflammation. A total number of 300 subjects will be randomized in 1:1 ratio to receive either mepolizumab or placebo along with existing standard of care therapy. The maximum study duration will be 56 weeks.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Mepolizumab 100 milligrams Drug: Placebo Drug: Salbutamol	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Eligible subjects will be randomized in 1:1 ratio to receive either mepolizumab or placebo along with existing standard of care therapy during the treatment period.Eligible subjects will be randomized in 1:1 ratio to receive either mepolizumab or placebo along with existing standard of care therapy during the treatment period.

Masking:

Double (Participant, Investigator)

Masking Description:

This will be a double blind study. Subjects and investigator will be masked.

Primary Purpose:

Treatment

Official Title:

A Randomized, Double Blind, Parallel Group Study of the Efficacy and Safety of Mepolizumab as Adjunctive Therapy in Patients With Severe Asthma With Eosinophilic Inflammation

Actual Study Start Date :

Aug 29, 2018

Anticipated Primary Completion Date :

Sep 7, 2022

Anticipated Study Completion Date :

Sep 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subjects receiving Mepolizumab Eligible subjects will randomized in 1:1 ratio to Mepolizumab group or Placebo group. Subjects in Mepolizumab group will receive Mepolizumab 100mg subcutaneously into the upper arm or thigh every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC of asthma treatment. Subjects will be provided with salbutamol MDIs as a rescue medication to be used on an needed basis in this study.	Drug: Mepolizumab 100 milligrams Mepolizumab will be given as a lyophilized cake in sterile vials for individual use. The vial will be reconstituted with Sterile Water for Injection, just prior to use. Drug: Salbutamol Salbutamol MDI will be given as a rescue medication to be used on an as needed basis in this study.
Placebo Comparator: Subjects receiving Placebo Eligible subjects in placebo group will receive placebo (0.9 percent sodium chloride) matching to Mepolizumab administered subcutaneously into the upper arm or thigh every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC of asthma treatment. Subjects will be provided with salbutamol MDIs as a rescue medication to be used on an as needed basis in this study.	Drug: Placebo Placebo will be given as 0.9 percent sodium chloride solution. Drug: Salbutamol Salbutamol MDI will be given as a rescue medication to be used on an as needed basis in this study.

Arm

Intervention/Treatment

Experimental: Subjects receiving Mepolizumab

Eligible subjects will randomized in 1:1 ratio to Mepolizumab group or Placebo group. Subjects in Mepolizumab group will receive Mepolizumab 100mg subcutaneously into the upper arm or thigh every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC of asthma treatment. Subjects will be provided with salbutamol MDIs as a rescue medication to be used on an needed basis in this study.

Drug: Mepolizumab 100 milligrams

Mepolizumab will be given as a lyophilized cake in sterile vials for individual use. The vial will be reconstituted with Sterile Water for Injection, just prior to use.

Drug: Salbutamol

Salbutamol MDI will be given as a rescue medication to be used on an as needed basis in this study.

Placebo Comparator: Subjects receiving Placebo

Eligible subjects in placebo group will receive placebo (0.9 percent sodium chloride) matching to Mepolizumab administered subcutaneously into the upper arm or thigh every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC of asthma treatment. Subjects will be provided with salbutamol MDIs as a rescue medication to be used on an as needed basis in this study.

Drug: Placebo

Placebo will be given as 0.9 percent sodium chloride solution.

Drug: Salbutamol

Salbutamol MDI will be given as a rescue medication to be used on an as needed basis in this study.

Outcome Measures

Primary Outcome Measures

Number of clinically significant exacerbations of asthma [Up to Week 52]
Clinically significant exacerbations are defined as worsening of asthma which requires use of systemic corticosteroids and/or hospitalizations and/or Emergency Department (ED) visits.

Secondary Outcome Measures

Time to first clinically significant exacerbations [Up to Week 52]
Clinically significant exacerbations are defined as worsening of asthma which requires use of systemic corticosteroids and/or hospitalizations and/or ED visits.
Mean change from Baseline in St. George's Respiratory Questionnaire (SGRQ) at Week 52 [Baseline and Week 52]
The SGRQ Questionnaire is a well-established, self-completed tool, comprising of 50 questions with 76 weighted responses designed to measure Quality of Life in subjects 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.
Number of exacerbations requiring hospitalization or ED visits [Up to Week 52]
An exacerbation is defined as worsening of asthma requiring the use of systemic corticosteroids and/or emergency department visit, or hospitalization. The number of exacerbations requiring hospitalization including intubation and admittance to an Intensive care unit (ICU) or ED visits will be evaluated.
Number of exacerbations requiring hospitalization [Up to Week 52]
An exacerbation is defined as worsening of asthma requiring the use of systemic corticosteroids and/or emergency department visit, or hospitalization.
Mean change from Baseline in clinic prebronchodilator forced expiratory volume in 1 second (FEV1) at Week 52 [Baseline and Week 52]
FEV1 is the volume of air that can be forced out in one second after taking a deep breath. FEV1 will be measured via spirometer at Baseline and Week 52.
Number of subjects with adverse events including systemic (i.e., allergic [type I hypersensitivity] and other systemic) and injection site reactions [Up to Week 52]
AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of subjects with adverse events including systemic and injection site reactions will be reported.
Number of subjects with abnormal hematology parameters [Up to Week 52]
Hematology parameters which will be assessed include platelet count, red blood cell (RBC) count, hemoglobin, hematocrit; RBC indices: mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH); white blood cell (WBC) count with differential: neutrophils, lymphocytes, monocytes, eosinophils and basophils.
Number of subjects with abnormal clinical chemistry parameters [Up to Week 52]
Clinical chemistry parameters which will be assessed include blood urea nitrogen, potassium, aspartate amino transferase (serum glutamic oxaloacetic transaminase), total and direct bilirubin, creatinine, sodium, alanine amino transferase (serum glutamic pyruvic transaminase), total protein, glucose, calcium, alkaline phosphatase and albumin.
Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP) [Up to Week 52]
SBP and DBP will be measured in a sitting position after 5 minutes rest.
Number of subjects with abnormal pulse rate [Up to Week 52]
Pulse rate measurement will be measured in a sitting position after 5 minutes rest.
Number of subjects with abnormal electrocardiogram (ECG) findings [Up to Week 52]
Twelve-lead ECG measurements will be obtained after the subject has rested in the supine position for 5 minutes.
Number of subjects with anti-mepolizumab antibody positive results [Up to Week 52]
Number of subjects with positive anti-mepolizumab antibody results will be determined.
Change from Baseline in blood eosinophil ratio [Baseline and Week 52]
Blood eosinophil counts will be recorded as part of standard hematological assessments.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects who will be able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
Subjects with at least 12 years of age at Visit 0 and a minimum weight of 40 kilograms.
Persistent airflow obstruction as indicated by: For subjects >=18 years of age at visit 1, a pre-bronchodilator FEV1 <80 percent predicted (National Health and Nutrition Examination Survey [NHANES] III).;For subjects 12 to 17 years of age at Visit 1: A pre-bronchodilator FEV1 <90 percent predicted (NHANES III) recorded at Visit 1 or FEV1: Forced vital capacity (FVC) ratio <0.8 recorded at Visit 1.
Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma as per Randomization Criteria 1 (Documented peripheral blood eosinophil count of >=300 cells per microliters that is related to asthma in the past 12 months prior to Visit 1 or a peripheral blood eosinophil count of >=150 cells per microliters at Visit 1 that is related to asthma).
Regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1, of which at least 9 months accumulated documented is required, the 3 months prior to Visit 1 is mandatory. With or without maintenance oral corticosteroids (OCS). ICS dose must be >=500 microgram per day fluticasone propionate (FP) or equivalent daily (for ICS/long-acting beta-2-agonists combination preparations, Seretide 50/250 micrograms twice daily and above or equivalent will meet this ICS criteria). (Maintenance OCS is defined as a prescribed regimen of a minimum average daily dose of prednisone 5 milligrams [or equivalent]).
Current treatment with an additional controller medication, besides ICS, for at least 3 months. (Example given [e.g.], long-acting beta-2-agonist, leukotriene receptor antagonist [LTRA], or theophylline).
Previously confirmed history of two or more exacerbations requiring treatment with systemic corticosteroid (intramuscular [IM], intravenous, or oral), in the 12 months prior to Visit 1, despite the use of high-dose ICS. For subjects receiving maintenance corticosteroid, the corticosteroid treatment for the exacerbations must have been a two-fold increase or greater in the dose for at least 3 days is required.
A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1 percent, during the intervention period and for at least 4 months after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.

A WOCBP must have a negative highly sensitive pregnancy test before the first dose of study intervention. If urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the subject must be excluded from participation if the serum pregnancy result is positive. Follicle-stimulating hormone will be assessed to confirm child-bearing status as needed in non WOCBP.

Exclusion Criteria:

Current smokers or former smokers with a smoking history of >=10 pack years (number of pack years = (number of cigarettes per day/20) x number of years smoked). A former smoker is defined as a subject who quit smoking at least 6 months prior to Visit 1.
Presence of a known pre-existing, clinically significant lung condition other than asthma, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study. This includes current bacterial or viral infection of the upper or lower respiratory tract, 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. Clinically Significant is defined as any disease/condition that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
A chest X-ray that reveals evidence of clinically significant abnormalities not believed to be due to the presence of asthma.
Bronchial Thermoplasty and Radiotherapy are excluded for 12 months prior to visit 1 and throughout the study.
A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Subjects that had localized carcinoma of the skin which was resected for cure will not be excluded).
Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice or cirrhosis. Subjects with ALT >2 times Upper Limit of Normal (ULN), bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent)
Subjects who have known, pre-existing severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to: known ejection fraction of <30 percent or severe heart failure meeting New York Heart Association Class IV classification or hospitalized in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III or angina diagnosed less than 3 months prior to Visit 1 or at Visit 1.
QT interval corrected by Fridericia's formula (QTc[F]) >450 milliseconds (msec) or QTc(F) >480 msec for subjects with Bundle Branch Block at Visit 1 is exclusive.
Subjects who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment. Current malignancy except for basal and squamous skin cancer.
Subjects with other conditions that could lead to elevated eosinophils such as Hypereosiniophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic Esophagitis.
Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also excluded.
A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1. Alcohol abuse is defined as: an average weekly intake of greater than 21 units or an average daily intake of greater than three units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than two units (females). One unit was equivalent to a half-pint (220 milliliters) of beer or one (25 milliliters) measure of spirits or one glass (125 milliliters) of wine.
A known immunodeficiency (e.g., human immunodeficiency virus - HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
Subjects who have received omalizumab (Xolair) within 130 days of Visit 1.
Subjects who have received any monoclonal antibodies (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
Use of herbals within 7 days prior to visit 1, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
Subjects who have received treatment with an investigational drug within the past 30 days or five terminal phase half-lives of the drug whichever is longer, prior to visit 1 (this also includes investigational formulations of marketed products).
Subjects with allergy/intolerance to a monoclonal antibody or biologic.
Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations.
Previously participated in any study with mepolizumab and received investigational product (including placebo).
A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study. Re-screening of subjects will be allowed only upon approval by the medical monitor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Fuzhou	Fujian	China	350001
2	GSK Investigational Site	Guangzhou	Guangdong	China	510080
3	GSK Investigational Site	Guangzhou	Guangdong	China	510120
4	GSK Investigational Site	Guangzhou	Guangdong	China	510150
5	GSK Investigational Site	Guangzhou	Guangdong	China	510630
6	GSK Investigational Site	Shen Zhen	Guangdong	China	518020
7	GSK Investigational Site	Zhanjiang	Guangdong	China	524001
8	GSK Investigational Site	Guiyang	Guizhou	China	550002
9	GSK Investigational Site	Shijiazhuang	Hebei	China	050000
10	GSK Investigational Site	Zhengzhou	Henan	China	450052
11	GSK Investigational Site	Wuhan	Hubei	China	430022
12	GSK Investigational Site	Hengyang	Hunan	China	421000
13	GSK Investigational Site	Hohhot	Inner Mongolia	China	010050
14	GSK Investigational Site	Huhhot	Inner Mongolia	China	010017
15	GSK Investigational Site	Nanjing	Jiangsu	China	210006
16	GSK Investigational Site	Wuxi	Jiangsu	China	214023
17	GSK Investigational Site	Changchun	Jilin	China	130021
18	GSK Investigational Site	Changchun	Jilin	China	130041
19	GSK Investigational Site	Shenyang	Liaoning	China	110004
20	GSK Investigational Site	Shenyang	Liaoning	China	110015
21	GSK Investigational Site	Yinchuan	Ningxia	China	750001
22	GSK Investigational Site	Jinan	Shandong	China	250012
23	GSK Investigational Site	Qingdao	Shandong	China	266071
24	GSK Investigational Site	Taiyuan	Shanxi	China	030000
25	GSK Investigational Site	Chengdu	Sichuan	China	610041
26	GSK Investigational Site	Urumqi	Xinjiang	China	830054
27	GSK Investigational Site	Hangzhou	Zhejiang	China	310006
28	GSK Investigational Site	Wenzhou	Zhejiang	China	323027
29	GSK Investigational Site	Beijing		China	100044
30	GSK Investigational Site	Beijing		China	100144
31	GSK Investigational Site	Beijing		China	100191
32	GSK Investigational Site	Changchun		China	130000
33	GSK Investigational Site	Changsha		China	410013
34	GSK Investigational Site	Guangzhou		China	511400
35	GSK Investigational Site	Hang Zhou		China	310005
36	GSK Investigational Site	Shanghai		China	200000
37	GSK Investigational Site	Shanghai		China	200032
38	GSK Investigational Site	Shanghai		China	200040
39	GSK Investigational Site	Shanghai		China	200233
40	GSK Investigational Site	Shanghai		China	200433
41	GSK Investigational Site	Suzhou		China	215004
42	GSK Investigational Site	Tianjin		China	300052
43	GSK Investigational Site	Tianjin		China	300211

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT03562195

Other Study ID Numbers:

201536

First Posted:

Jun 19, 2018

Last Update Posted:

Jul 6, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by GlaxoSmithKline

Eosinophilic inflammation

Mepolizumab

Asthma

Additional relevant MeSH terms:

Asthma

Albuterol

Study Results

No Results Posted as of Jul 6, 2022