Phase 3
Completed N=651
A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects
Source: ClinicalTrials.gov NCT01842607 ↗Enrolled (actual)
651
Serious AEs
14.4%
Results posted
Mar 2016
Primary outcomePrimary: Number of Participants With Adverse Events (AEs) Including Both Systemic (i.e. Allergic/Immunoglobulin (Ig)E-mediated and Non-allergic) and Local Site Reactions — 558; 119; 94; 1 Participants
Summary
This is a multi-centre, open-label long-term safety study of 100 milligram (mg) mepolizumab administered subcutaneously (SC) every 4 weeks for 12 months in addition to standard of care in subjects who have severe, refractory asthma and a history of eosinophilic inflammation. Subjects who completed either MEA115588 or MEA115575 will be offered the opportunity to consent for this study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) Including Both Systemic (i.e. Allergic/Immunoglobulin (Ig)E-mediated and Non-allergic) and Local Site Reactions |
558; 119; 94; 1; 0 | — |
| SECONDARY Number of Participants With Positive Anti-mepolizumab Binding Antibodies and Neutralizing Antibodies (NAb) at the Indicated Time Points |
31; 615; 0; 31 | — |
| SECONDARY Annualized Rate of Exacerbations Per Year |
0.93 | — |
| SECONDARY Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score |
-0.09; -0.11; -0.05; -0.10; -0.09; 0.20 | — |
| SECONDARY Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period |
67; 50; 29 | — |
| SECONDARY Number of Participants Withdrawn Due to Lack of Efficacy and Adverse Events From the Study |
19; 11 | — |
| SECONDARY Number of Participants Hospitalized Due to Exacerbations and Adverse Events |
612; 29; 4; 4; 0; 0 | — |
| SECONDARY Number of Participants With Systemic (i.e., Allergic/IgE-mediated and Non-allergic) and Local Site Reactions |
13; 7; 4; 3; 29 | — |
| SECONDARY Number of Participants With Electrocardiogram (ECG) Findings at Any Time Post Baseline |
262; 295; 81 | — |
| SECONDARY Mean Change From Baseline in QT Interval Corrected by Bazett's Method (QTcB) and QT Interval Corrected by Fridericia's Method (QTcF) Values for ECG Assessed at Baseline, Week 28, Week 52 and at Follow-up Visit (Approx. 12 Weeks Post-last Dose) |
-5.5; -3.2; -3.4; -7.1; -3.5; -5.5 | — |
| SECONDARY Number of Participants With Maximum Change From Baseline in QTcF Interval for ECG Assessed at Any Time Post Baseline |
2; 11; 252; 328; 20; 1 | — |
| SECONDARY Number of Participants With Maximum Change From Baseline in QTcB Interval for ECG Assessed at Any Time Post Baseline |
3; 16; 222; 330; 41; 2 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Assessed at Week 52 |
0.3; -0.4 | — |
| SECONDARY Change From Baseline in Pulse Rate Assessed at Week 52 |
0.2 | — |
| SECONDARY Number of Participants With Clinical Chemistry Parameters Outside the Normal Range at Any Time Post-baseline |
70; 1; 23; 37; 53; 38 | — |
| SECONDARY Number of Participants With Haematology Laboratory Parameters Outside the Normal Range at Any Time Post-baseline |
2; 3; 52; 36; 25; 146 | — |
Eligibility Criteria
Inclusion Criteria
- French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
- Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent.
- MEA115588 or MEA115575 study completion: Completion of the double-blind investigational product treatment during MEA115588 or MEA115575.
- Current Anti-Asthma Therapy: Asthma is currently being treated with a controller medication (i.e., inhaled corticosteroids [ICS] or other asthma controlled medication) and the subject has been on a controller medication for the past 12 weeks. Subjects will be expected to continue controller therapy for the duration of the study.
- Male or eligible female subjects:
- To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control for the duration of the trial and for 4 months after the last study drug administration.
- A serum pregnancy test is required of all females at the initial Baseline Visit (Visit 1). In addition, a urine pregnancy test will be performed for all females prior to enrollment, during each scheduled study visit prior to the injection of investigational product, and during the Follow-up Visit.
Exclusion Criteria
- Hypersensitivity: Hypersensitivity reaction related to study medication during the MEA115588 or MEA115575 that led to patient withdrawal. Subjects who experienced a localized injection site reaction do not need to be excluded.
- Health Status: Clinically significant change in health status during MEA115588 or MEA115575 which in the opinion of the investigator would make the subject unsuitable for participation in this long-term study.
- Malignancy: A current malignancy or malignancy that developed during MEA115588 or MEA115575 (subjects that had localized carcinoma of the skin which was resected for cure will not be excluded). [Note for South Korea: Korean subjects with a diagnosis of malignancy within 5 years are excluded]
- Prior SAE: A study related SAE in MEA115588 or MEA115575 that was assessed as possibly related to study medication by the investigator.
- Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
- ECG: Baseline ECG which has a clinically significant abnormality or which shows corrected QT interval with Fridericia (QTcF) >=450 millisecond (msec) or QTcF >=480 msec for subjects with Bundle Branch Block.
- Smoking status: Current smokers
- Liver Function: Liver function tests that meet any of the following during one of the last treatment visits in MEA115588 or MEA115575 : alanine transaminase (ALT) >=2 x upper limit of normal (ULN); aspartate transaminase (AST) >=2 x ULN; alkaline phosphatase >=2 x ULN; Bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%
- Hepatitis Status: Positive Hepatitis B Surface Antigen (HBsAg) screen at Visit 1
- ECG Over-read: Clinically significant abnormality identified during the central over-read during one of the last treatment visits in MEA115588 or MEA115575
Data sourced from ClinicalTrials.gov (NCT01842607). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.