Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Subjects With Severe Uncontrolled Refractory Asthma

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Asthma

Treatments: Drug: SC Placebo; Drug: IV Placebo; Drug: Mepolizumab SC; Drug: Mepolizumab IV

Study type: Interventional

Funder types: Industry

Identifiers

NCT01691521

115588

Details and patient eligibility

About

This study will evaluate two dose regimens of mepolizumab [75mg intravenous (i.v.) or 100mg subcutaneous (SC) every 4 weeks] compared with placebo over a 32 week treatment period in subjects with severe refractory asthma with elevated blood eosinophils. Efficacy will be measured by a reduction in the frequency of asthma exacerbations. Additional efficacy assessments will include measurements of lung function, symptom scores, and quality of life. Safety will be assessed by clinical laboratory samples, ECGs, immunogenicity and adverse events.

This study is intended to replicate the Phase IIb/III study MEA112997. Subjects in MEA115588, who meet all eligibility criteria at screening visit, will enter the run-in period. Those subjects that are not able/eligible to be randomised at the end of the 6 week run-in period will be deemed run-in failures. Subjects will remain on their current maintenance therapy throughout the run-in, double-blind treatment administration and follow-up periods. Subjects who meet the randomisation eligibility criteria will be randomised in a 1:1:1 ratio to receive one of the following treatments every 4 weeks for a total of 8 doses: Mepolizumab 75 miligram (mg) i.v. and placebo SC, or Mepolizumab 100 mg SC and placebo i.v. or Placebo i.v. and placebo SC.

Subjects that receive all 8 doses of double-blind treatment, and meet the eligibility criteria for the Open-Label Extension (OLE) Study, will be offered the opportunity to participate in the OLE trial.

Enrollment: 580 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Able to give written informed consent prior to participation in the study
• At least 12 years of age at visit 1 and a minimum weight of 45 kilogram (kg)
• A well-documented requirement for regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS)
• Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months
• Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma
• At Visit 1, a pre-bronchodilator FEV1 <80% (for subjects >= 18 years of age), a pre-bronchodilator FEV1 <90% or FEV1:FVC ratio <0.8 (for subjects 12-17 years of age).
• Previously confirmed history of two or more exacerbations requiring treatment with systemic CS
• Male or Eligible Female (females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control)
• French subjects will be included only if either affiliated to or a beneficiary of a social security category.

Exclusion criteria

• Current smokers or former smokers with a smoking history of >=10 pack years
• Presence of a known pre-existing, clinically important lung condition other than asthma
• A current malignancy or previous history of malignancy in less than 12 months
• Known, pre-existing, unstable liver disease cirrhosis and known biliary abnormalities
• Known, pre-existing severe or clinically significant cardiovascular disease
• known, pre-existing other concurrent clinically significant medical conditions that are uncontrolled with standard treatment
• Subjects with any eosinophilic diseases
• QTc(F) ≥450msec or QTc(F) ≥480 msec
• A history of alcohol/substance abuse
• Subject with known immunodeficiency
• Subjects who have received omalizumab within 130 days of Visit 1 or any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1
• 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
• Subjects with allergy/intolerance to a monoclonal antibody or biologic.
• Subjects who are pregnant or breastfeeding
• 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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580 participants in 3 patient groups, including a placebo group

Mepolizumab IV

Experimental group

Description:

Mepolizumab 75 mg will be administered intravenously approximately every 4 weeks with the last dose at week 32. Subjects in the Mepolizumab IV arm will receive mepolizumab 75 mg intravenously and placebo SC once every 4 weeks with the last dose at Week 28 (total of 8 doses)

Treatment:

Drug: Mepolizumab IV

Drug: SC Placebo

Mepolizumab SC

Experimental group

Description:

Subjects in the Mepolizumab SC arm will receive mepolizumab 100 mg SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)

Treatment:

Drug: Mepolizumab SC

Drug: IV Placebo

Placebo

Placebo Comparator group

Description:

Subjects in the Placebo arm will receive matching placebo SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)

Treatment:

Drug: IV Placebo

Drug: SC Placebo