Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma
| Status: | Completed |
|---|---|
| Conditions: | Asthma |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 12 - Any |
| Updated: | 4/21/2016 |
| Start Date: | October 2012 |
| End Date: | December 2013 |
MEA115575: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study of Mepolizumab Adjunctive Therapy to Reduce Steroid Use in Subjects With Severe Refractory Asthma
This is a randomised, double-blind, placebo-controlled, parallel-group, multicenter study of
mepolizumab in comparison with placebo in reducing Oral Corticosteroid (OCS) use in subjects
with severe refractory asthma. The study consists of four phases, OCS Optimisation Phase
(Week -8 to Week 0), and the double-blind treatment period divided into an Induction Phase
(Week 0 to Week 4), OCS Reduction Phase (Week 5 upto Week 20) followed by Maintenance Phase
(Week 20 to Week 24). During the Optimisation Phase the investigator will adjust the OCS
(prednisone/prednisolone) dose according to the Optimisation titration schedule based on a
review of Asthma Control Questionnaire (ACQ)-5 score and exacerbation. In the Induction
Phase subjects will be randomized 1:1 (approximately 60 per arm) to receive either
mepolizumab (100 mg) administered subcutaneously (SC) or placebo every 4 weeks in addition
to their existing maintenance asthma therapy with the lowest dose of OCS from Optimisation
Phase. The Induction Phase will allow sufficient time for those subjects randomised to the
mepolizumab arm to achieve a decrease in the eosinophilic inflammation prior to the
reduction in OCS. During the Reduction Phase, subjects will continue receiving 100 mg
mepolizumab/placebo every 4 weeks and the OCS dose reduction will be done every 4 weeks
using the reduction titration schedule based on a review of eDiary parameters recorded by
the subject, the subjects' exacerbation history, and a review of the signs and symptoms of
adrenal insufficiency. In the Maintenance Phase subjects will be maintained without any
further OCS dose adjustment. Subjects who complete the 24 week double-blind period and meet
the eligibility criteria, will be offered the opportunity to participate in an open label
extension (OLE) study otherwise they will return for a Follow-up Visit 12 weeks after their
last dose of double blind study treatment. At each clinic visit, adverse events, safety
labs, spirometery parameters and exacerbations will be assessed. The pharmacokinetic samples
will be collected in the beginning of the treatment, prior to last dose, at the end of study
(exit visit) and the follow up.
mepolizumab in comparison with placebo in reducing Oral Corticosteroid (OCS) use in subjects
with severe refractory asthma. The study consists of four phases, OCS Optimisation Phase
(Week -8 to Week 0), and the double-blind treatment period divided into an Induction Phase
(Week 0 to Week 4), OCS Reduction Phase (Week 5 upto Week 20) followed by Maintenance Phase
(Week 20 to Week 24). During the Optimisation Phase the investigator will adjust the OCS
(prednisone/prednisolone) dose according to the Optimisation titration schedule based on a
review of Asthma Control Questionnaire (ACQ)-5 score and exacerbation. In the Induction
Phase subjects will be randomized 1:1 (approximately 60 per arm) to receive either
mepolizumab (100 mg) administered subcutaneously (SC) or placebo every 4 weeks in addition
to their existing maintenance asthma therapy with the lowest dose of OCS from Optimisation
Phase. The Induction Phase will allow sufficient time for those subjects randomised to the
mepolizumab arm to achieve a decrease in the eosinophilic inflammation prior to the
reduction in OCS. During the Reduction Phase, subjects will continue receiving 100 mg
mepolizumab/placebo every 4 weeks and the OCS dose reduction will be done every 4 weeks
using the reduction titration schedule based on a review of eDiary parameters recorded by
the subject, the subjects' exacerbation history, and a review of the signs and symptoms of
adrenal insufficiency. In the Maintenance Phase subjects will be maintained without any
further OCS dose adjustment. Subjects who complete the 24 week double-blind period and meet
the eligibility criteria, will be offered the opportunity to participate in an open label
extension (OLE) study otherwise they will return for a Follow-up Visit 12 weeks after their
last dose of double blind study treatment. At each clinic visit, adverse events, safety
labs, spirometery parameters and exacerbations will be assessed. The pharmacokinetic samples
will be collected in the beginning of the treatment, prior to last dose, at the end of study
(exit visit) and the follow up.
Inclusion Criteria:
- Informed Consent and Study Compliance: Subjects must 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.
- Systemic Corticosteroids: Requirement for regular treatment with maintenance systemic
corticosteroids in the 6 months prior to Visit 1 and using a stable oral
corticosteroid dose for 4 weeks prior to Visit 1. Subjects must be taking 5.0 to 35
mg/day of prednisone or equivalent at Visit 1 and must agree to switch to study
required prednisone/prednisolone as their oral corticosteroid and use it per protocol
for the duration of the study.
- Inhaled Corticosteroids: Requirement for regular treatment with high dose inhaled
corticosteroid in the 6 months prior to Visit 1. For 18 years of age and older:
inhaled corticosteroid (ICS) dose must be >=880 microgram (µg)/day fluticasone
propionate (FP) (ex-actuator) or equivalent daily. For ICS/ long acting beta2 agonist
(LABA) combination preparations, the highest approved maintenance dose in the local
country will meet this ICS criterion. For ages 12 to 17: ICS dose must be >=440
μg/day FP (ex-actuator) or equivalent daily.
- Controller Medication: Current treatment with an additional controller medication for
at least 3 months OR documentation of having used and failed an additional controller
medication for at least 3 successive months during the prior 12 months [e.g., LABA,
leukotriene receptor antagonist (LTRA), or theophylline].
- Eosinophilic Asthma: Prior documentation of eosinophilic asthma or high likelihood of
eosinophilic asthma.
- FEV1: Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 <80%
predicted.
- Asthma: Evidence of asthma indicated by airway reversibility, hyperresponsiveness or
airway variability.
Exclusion Criteria:
- Smoking history: Current smokers or former smokers with a smoking history of >=10
pack years.
- Concurrent Respiratory Disease: Presence of a clinically important lung condition
other than asthma.
- Malignancy: A current malignancy or previous history of cancer in remission for less
than 12 months prior screening
- Liver Disease: Unstable liver disease
- Cardiovascular: Subjects who have severe or clinically significant cardiovascular
disease uncontrolled with standard treatment.
- Other Concurrent Medical Conditions: Subjects 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: Subjects with other conditions that could lead to elevated
eosinophils such as Hypereosiniophilic Syndromes, including Churg-Strauss Syndrome,
or Eosinophilic Esophaghitis. Subjects with a known, pre-existing parasitic
infestation within 6 months prior to Visit 1 are also to be excluded.
- ECG: ECG assessment QTcF >=450 milliseconds (msec) or QTcF >= 480 msec for subjects
with Bundle Branch Block.
- Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus - HIV),
other than that explained by the use of corticosteroids taken as therapy for asthma.
- Omalizumab Use: Subjects who have received omalizumab [Xolair] within 130 days of
Visit 1.
- Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody
(other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
- Investigational Medications: 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, prior to Visit 1 (this also includes investigational
formulations of marketed products).
- Hypersensitivity: Subjects with a known allergy or intolerance to a monoclonal
antibody or biologic.
- Pregnancy: Subjects who are pregnant or breastfeeding. Patients should not be
enrolled if they plan to become pregnant during the time of study participation.
- Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or
substance abuse within 2 years prior to Visit 1.
- Adherence: Subjects who have known evidence of lack of adherence to controller
medications and/or ability to follow physician's recommendations.
- Previous participation: Subjects who have previously any study of mepolizumab and
received Investigational Product.
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