Efficacy and Safety Study of Mepolizumab 100 Milligram (mg) Subcutaneous (SC) in Indian Participants Aged Greater Than or Equal to (>=) 18 Years With Severe Eosinophilic Asthma

NCT04276233 | Completed Phase 4 Results

• 1 other identifier: 209682
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 14

Brief Summary

Mepolizumab is a humanized monoclonal antibody (IgG1, kappa) that blocks interleukin- 5 (IL-5) thus inhibits production and survival of eosinophils. The aim of this phase 4, open-label, single-arm study is to evaluate the safety and efficacy of Mepolizumab 100 mg SC administered every 4 weeks in Indian participants aged 18 years or above with severe eosinophilic asthma. After the first dose of mepolizumab, participants will receive 5 more doses of mepolizumab at 4 weekly intervals. Following the last dose of mepolizumab, the end of the study Visit will occur 4 weeks later. During the treatment period, OCS use and dose adjustment in participants will be as per the investigator's discretion and clinical practice.

Conditions

Asthma

Keywords

Mepolizumab; Oral corticosteroids; Prednisolone; Prednisone; Severe Eosinophilic asthma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward medical occurrence that, at any dose that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment was categorized as SAE. Adverse events which were not serious were considered as non-serious adverse events. Number of participants with SAEs and common (greater than equal to \[\>=\] 3 percent \[%\]) non-SAEs were reported.

  Up to Week 24

• Number of Participants With Adverse Events of Special Interest (AESIs)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs were adverse events associated with the identified and potential risks of mepolizumab. AESIs were systemic/ local site reactions, all infections (Infections from Infections and infestations System Organ Class \[SOC\]), opportunistic infections, neoplasm, malignancies, cardiac disorders and serious cardiac, vascular and thromboembolic (CVT) events.

  Up to Week 24

Secondary Outcomes (7)

• Number of Participants With Clinically Significant Exacerbations (Including Exacerbations Requiring Hospitalization or Emergency Department [ED Visits])

  Up to Week 24

• Number of Participants With Exacerbations Requiring Hospitalization or ED Visits

  Up to Week 24

• Number of Participants With Exacerbations Requiring Hospitalization

  Up to Week 24

• Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 24

  Baseline (Weeks -2 to -1) and Week 24

• Change From Baseline in Clinic Post-bronchodilator FEV1 at Week 24

  Baseline (Weeks -2 to -1) and Week 24

Study Arms (1)

Participants with severe eosinophilic asthma

EXPERIMENTAL

Participants with severe eosinophilic asthma will receive Mepolizumab 100 mg subcutaneously into the upper arm or thigh every 4 weeks for a period of 24 weeks (total of 6 doses). Salbutamol metered dose inhalers (MDIs) will be provided as rescue medication during treatment period.

Drug: Mepolizumab; Drug: Salbutamol

Interventions

Mepolizumab DRUG

Mepolizumab will be available as a lyophilized cake in sterile vials and will be reconstituted with sterile water for injection, just prior to use.

Participants with severe eosinophilic asthma

Salbutamol DRUG

Salbutamol metered dose inhalers (MDIs) will be provided as rescue medication during treatment period.

Participants with severe eosinophilic asthma

Eligibility Criteria

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

You may qualify if:

• Participant must be greater than or equal to (≥) 18 to 65 years of age inclusive, at the time of signing the informed consent.
• Asthma: Evidence of asthma as documented by either: (a) Airway reversibility (FEV1\>=12% and 200 milliliter (ml) demonstrated at Visit 1 (screening) or Visit 2 (Week 0) OR documented in the previous 12 months OR (b) Airway hyperresponsiveness (methacholine: PC20 of \<8mg/mL or histamine: PD20 of \<7.8 μmol; mannitol: decrease in FEV1 as per the labelled product instructions) documented in the 12 months prior to Visit 2 (Week 0) OR (c) Airflow variability in clinic FEV1 \>=20% between two consecutive clinic visits documented in the 12 months prior to Visit 2 (FEV1 recorded during an exacerbation should not be considered for this criteria) OR (d) Airflow variability as indicated by \>20% diurnal variability in peak flow observed on 3 or more days during the optimization period.
• Participants with Eosinophilic asthma: prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma as FEV1: Persistent airflow obstruction as indicated by: For participants \>=18 years of age at Visit 1 (screening) or Visit 2 (Week 0), a pre- bronchodilator FEV1 \<80% predicted. For predicted FEV1 values National Health and Nutrition Examination Survey (NHANES) III values will be used and adjustments to these values will be made for race.
• Eosinophilic Phenotype: Airway inflammation characterized as eosinophilic in nature as indicated by one of the following characteristics: (a) An elevated peripheral blood eosinophil level of \>=300 cells/microliter(μL) that is related to asthma within the previous 12 months prior to Visit 2 (Week 0). OR (b) Peripheral baseline eosinophil level \>=150 cells/μL between Visit 1 (screening) and Visit 2 (Week 0) that is related to asthma.
• Participants eligible for mepolizumab treatment as per independent clinical judgment of treating physician in alignment with local prescribing information.
• Inhaled Corticosteroids: requirement for regular treatment with high dose inhaled corticosteroid in the 6 months prior to Visit 1 (screening). For 18 years of age and older: Inhaled corticosteroids (ICS) dose must be \>=880 microgram (mcg)/day fluticasone propionate (FP) (ex-actuator) or equivalent daily.
• Controller Medication: Current treatment with an additional controller medication for at least 3 months OR having used and failed an additional controller medication for at least 3 successive months during the prior 12 months \[e.g., long-acting beta2-agonist (LABA), leukotriene receptor antagonist (LTRA), or theophylline\].
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Treatment Period Criteria
• Eosinophilic asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma.
• eDiary Compliance: Compliance with completion of the eDiary defined as: (a) Completion of symptom scores on 4 or more days out of the last 7 days immediately preceding Visit 2 (Week 0). (b) Completion of information relating to rescue medication use on 4 or more days out of the last 7 days immediately preceding Visit 2 (Week 0). (c) Completion of PEF measurements on 4 or more days out of the last 7 days immediately preceding Visit 2 (Week 0).

You may not qualify if:

• Concurrent Respiratory Disease: Presence of a 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.
• Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior screening (Participants who had localized carcinoma (i.e. basal or squamous cell) of the skin which was resected for cure will not be excluded).
• Liver Disease: Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Cardiovascular: Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to: (a) known ejection fraction of \<30% OR (b) severe heart failure meeting New York Heart Association Class IV OR (c) hospitalized in the 12 months prior to Visit 1 (screening) for severe heart failure meeting New York Heart Association Class III OR (d) angina diagnosed less than 3 months prior to Visit 1 (screening) or at Visit 1.
• Other Concurrent Medical Conditions: Participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
• Eosinophilic Diseases: Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic Esophaghitis. Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 (screening) are also to be excluded.
• Omalizumab Use: Participants who have received omalizumab within 130 days of Visit 1 (screening).
• Other Monoclonal Antibodies: Participants who have received any monoclonal antibody (other than omalizumab) to treat inflammatory disease within 5 half-lives of Visit 1 (screening).
• Investigational Medications: Participants 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).
• Participants who have previously participated in any study of mepolizumab and received Investigational Product (including placebo).
• ECG: ECG assessment QTcF \> 450msec or QTcF \> 480 msec for participants with Bundle Branch Block. Participants are excluded if an abnormal 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.
• Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus - HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
• Smoking history: Current smokers or former smokers with a smoking history of \>=10 pack years. A former smoker is defined as a participant who quit smoking at least 6 months prior to Visit 1 (screening).
• Hypersensitivity: Participants with a known allergy or intolerance to a monoclonal antibody or biologic.
• Pregnancy: Participants who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Tech Observer: collaborator

Study Sites (14)

GSK Investigational Site

Ahmedabad, 380013, India

Location

GSK Investigational Site

Ahmedabad, 380052, India

Location

GSK Investigational Site

Byculla Mumbai, 400008, India

Location

GSK Investigational Site

Hyderabad, 500018, India

Location

GSK Investigational Site

Hyderabad, 500038, India

Location

GSK Investigational Site

Hyderabad, 500082, India

Location

GSK Investigational Site

Jaipur, 302039, India

Location

GSK Investigational Site

Kanpur, 208005, India

Location

GSK Investigational Site

Kolkata, 700014, India

Location

GSK Investigational Site

Nagpur, 440012, India

Location

GSK Investigational Site

New Delhi, 110096, India

Location

GSK Investigational Site

Noida, 201301, India

Location

GSK Investigational Site

Pune, 411001, India

Location

GSK Investigational Site

Pune, 411004, India

Location

MeSH Terms

Conditions

Asthma; Pulmonary Eosinophilia

Interventions

mepolizumab; Albuterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic 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 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm study

Study Record Dates

• First Submitted: February 17, 2020
• First Posted: February 19, 2020
• Study Start: June 29, 2021
• Primary Completion: October 28, 2023
• Study Completion: October 28, 2023
• Last Updated: December 10, 2024
• Results First Posted: December 10, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.

Locations

IN (14)