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

NCT03562195 | Completed Phase 3 Results

• 1 other identifier: 201536
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 42

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.

Conditions

Asthma

Keywords

Eosinophilic inflammation; Mepolizumab; Asthma

Outcome Measures

Primary Outcomes (1)

• Rate of Clinically Significant Exacerbations of Asthma

  Clinically significant exacerbation is defined as worsening of asthma which requires use of systemic corticosteroids and/or hospitalizations and/or Emergency Department (ED) visits. Analysis of the number of exacerbations was performed using a negative binomial model with covariates of treatment group, baseline maintenance Oral Corticosteroids (OCS) therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted Forced Expiratory Volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable.

  Up to Week 52

Secondary Outcomes (18)

• Percent Probability of First Clinically Significant Exacerbations at Week 16, Week 32, and Week 52

  Week 16, 32 and 52

• Mean Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) at Week 52

  Baseline and Week 52

• Number of Participants With Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or Emergency Department (ED) Visits

  Up to Week 52

• Number of Participants With Clinically Significant Exacerbations Requiring Hospitalization

  Up to Week 52

• Mean Change From Baseline in Clinic Prebronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52

  Baseline and Week 52

Study Arms (2)

Mepolizumab 100mg

EXPERIMENTAL

Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.

Drug: Mepolizumab 100 milligrams; Drug: Salbutamol

Placebo

PLACEBO COMPARATOR

Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis

Drug: Placebo; Drug: Salbutamol

Interventions

Mepolizumab 100 milligrams DRUG

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.

Mepolizumab 100mg

Placebo DRUG

Placebo will be given as 0.9 percent sodium chloride solution.

Placebo

Salbutamol DRUG

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

Mepolizumab 100mg; Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (42)

GSK Investigational Site

Fuzhou, Fujian, 350001, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510080, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510120, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510150, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510630, China

Location

GSK Investigational Site

Shenzhen, Guangdong, 518020, China

Location

GSK Investigational Site

Zhanjiang, Guangdong, 524001, China

Location

GSK Investigational Site

Guiyang, Guizhou, 550002, China

Location

GSK Investigational Site

Shijiazhuang, Hebei, 050000, China

Location

GSK Investigational Site

Zhengzhou, Henan, 450052, China

Location

GSK Investigational Site

Wuhan, Hubei, 430022, China

Location

GSK Investigational Site

Hengyang, Hunan, 421000, China

Location

GSK Investigational Site

Hohhot, Inner Mongolia, 010017, China

Location

GSK Investigational Site

Hohhot, Inner Mongolia, 010050, China

Location

GSK Investigational Site

Nanjing, Jiangsu, 210006, China

Location

GSK Investigational Site

Wuxi, Jiangsu, 214023, China

Location

GSK Investigational Site

Changchun, Jilin, 130021, China

Location

GSK Investigational Site

Changchun, Jilin, 130041, China

Location

GSK Investigational Site

Shenyang, Liaoning, 110004, China

Location

GSK Investigational Site

Shenyang, Liaoning, 110015, China

Location

GSK Investigational Site

Yinchuan, Ningxia, 750001, China

Location

GSK Investigational Site

Jinan, Shandong, 250012, China

Location

GSK Investigational Site

Qingdao, Shandong, 266071, China

Location

GSK Investigational Site

Taiyuan, Shanxi, 030000, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610041, China

Location

GSK Investigational Site

Ürümqi, Xinjiang, 830054, China

Location

GSK Investigational Site

Hangzhou, Zhejiang, 310006, China

Location

GSK Investigational Site

Wenzhou, Zhejiang, 323027, China

Location

GSK Investigational Site

Beijing, 100044, China

Location

GSK Investigational Site

Beijing, 100144, China

Location

GSK Investigational Site

Beijing, 100191, China

Location

GSK Investigational Site

Changsha, 410013, China

Location

GSK Investigational Site

Guangzhou, 511400, China

Location

GSK Investigational Site

Hangzhou, 310005, China

Location

GSK Investigational Site

Shanghai, 200000, China

Location

GSK Investigational Site

Shanghai, 200032, China

Location

GSK Investigational Site

Shanghai, 200040, China

Location

GSK Investigational Site

Shanghai, 200233, China

Location

GSK Investigational Site

Shanghai, 200433, China

Location

GSK Investigational Site

Suzhou, 215004, China

Location

GSK Investigational Site

Tianjin, 300052, China

Location

GSK Investigational Site

Tianjin, 300211, China

Location

Related Publications (2)

• Chen R, Wei L, Dai Y, Wang Z, Yang D, Jin M, Xiong C, Li T, Hu S, Song J, Chan R, Kumar S, Abdelkarim A, Zhong N. Efficacy and safety of mepolizumab in a Chinese population with severe asthma: a phase III, randomised, double-blind, placebo-controlled trial. ERJ Open Res. 2024 May 20;10(3):00750-2023. doi: 10.1183/23120541.00750-2023. eCollection 2024 May.

  PMID: 38770009 BACKGROUND

• Chen R, Dai Y, Yang D, Liu C, Han W, Gu W, Cao J, Zhou Q, Howarth P, Weng S, Xiong C, Huang J, Liang P, Zhong N; 201536 Study Group. Clinical Remission Outcome in Chinese Patients With Severe Asthma With an Eosinophilic Phenotype Receiving Mepolizumab: A Post-hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial. Allergy Asthma Immunol Res. 2025 Jul;17(4):473-485. doi: 10.4168/aair.2025.17.4.473.

  PMID: 40736776 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Albuterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double blind study. Subjects and investigator will be masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 22, 2018
• First Posted: June 19, 2018
• Study Start: August 29, 2018
• Primary Completion: September 7, 2022
• Study Completion: September 7, 2022
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

CN (42)