Health Condition 1: J00-J99- Diseases of the respiratory system
Conditions
Interventions
Intervention1: Mepolizumab: Type - Biologic
Unit Dose Strength(s)- 100 mg/ml
Dosage Level(s)- 100 mg every 4 weeks
Route of Administration- subcutaneous
Study Intervention will
be provided in ampule.
Sponsors
GlaxosmithKline
Eligibility
Inclusion criteria
Inclusion criteria: Age1.Participant must be =18 to 65 years of age inclusive, at the time of signing the informed consent.Type of Participant and Disease Characteristics2.Asthma: Evidence of asthma as documented by either: •Airway reversibility (FEV1=12% and 200 ml) demonstrated at Visit 1 (screening), or Visit 2 (Week 0) OR documented in the previous 12 months OR•Airway hyper-responsiveness (methacholine: PC20 of 20% diurnal variability in peak flow observed on 3 or more days during the optimisation period3.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 6.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:•ICS dose must be =880 mcg/day fluticasone propionate (FP) (ex-actuator) or equivalent daily. 7.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]. Sex 8.Male or eligible female:Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:a.Is not a woman of childbearing potential (WOCBP) ORb.Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Appendix 4 during the intervention period and for at least 16 weeks 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.c. A WOCBP must have a negative highly sensitive (Appendix 2) pregnancy test (serum) within 8 weeks before the first dose of study intervention.d. Additional requirements for pregnancy
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1.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. 2.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). 3.Liver Disease: Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones). 4.Cardiovascular: Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to: •known ejection fraction of •severe heart failure meeting New York Heart Association Class IV (Appendix 5) OR •hospitalised in the 12 months prior to Visit 1 (screening) for severe heart failure meeting New York Heart Association Class III (Appendix 5) OR •angina diagnosed less than 3 months prior to Visit 1 (screening) or at Visit 1 5.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. 6.Eosinophilic Diseases: Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic Esophaghitis. 7.Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 (screening) are also to be excluded. Prior/Concomitant Therapy 8.Omalizumab Use: Participants who have received omalizumab [Xolair] within 130 days of Visit 1 (screening) 9.Other Monoclonal Antibodies: Participants who have received any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1 (screening) 10.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). Prior/Concurrent Clinical Study Experience 11.Participants who have previously participated in any study of mepolizumab and received Investigational Product (including placebo). Diagnostic assessments 12.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. 13.Immunodeficiency: A known immuno
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate safety, and tolerability of mepolizumab in participants with severe refractory asthma with elevated eosinophilsTimepoint: •Incidence of on-treatment adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs). AEs will be defined as on-treatment between the first dose up to and including 28 days following the last dose of mepolizumab. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objective-To evaluate efficacy of mepolizumab in participants with severe refractory asthma with elevated eosinophilsTimepoint: •No. of exacerbations requiring hospitalization/ED visits •Change from baseline in clinic prebronchodilator FEV1 at week 24 •Change from baseline in clinic postbronchodilator FEV1 at week 24 •Change from baseline in ACQ-5 score at week 24 •Change from baseline in morning PEF during weeks 20-24 •Achieving at least 50% reduction in OCS dose during weeks 20-24 compared to the baseline dose while maintaining asthma control | — |
Countries
India
Contacts
Public ContactDisha Gupta
GSK
Outcome results
None listed