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Trial record 3 of 19 for:    mepolizumab | Recruiting, Not yet recruiting, Active, not recruiting, Enrolling by invitation Studies

Cessation Versus Continuation of Long-term Mepolizumab in Severe Eosinophilic Asthma Patients

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ClinicalTrials.gov Identifier: NCT02555371
Recruitment Status : Active, not recruiting
First Posted : September 21, 2015
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:

Primary objective of the study is to evaluate whether patients with severe eosinophilic asthma who have received long-term treatment with mepolizumab (at least 3 years) need to maintain treatment with mepolizumab to continue to receive benefit. Subjects who participated in the open-label studies MEA115666 or 201312 with at least 6 months of treatment with mepolizumab prior to Visit 1 and who have no more than 2 consecutive missed doses of mepolizumab treatment will be eligible to participate in this study. This study will be conducted in 4 parts in approximately 300 subjects. Part A will be Variable Open-Label Run-in (for subjects with less than 3 years of mepolizumab treatment). Once the required 3 year exposure is reached, subjects will enter Part B- Fixed Open-Label Run-In (4 weeks to 8 weeks). During Part A and B subjects will be administered Open-label mepolizumab (100 milligram [mg] Subcutaneous [SC]) every 4 weeks. Part C will be the randomized double-blinded part. Upon completion of Part B, eligible subjects will be randomized to mepolizumab (100 mg SC) every 4 weeks or placebo administered SC every 4 weeks for 52 weeks.

Subjects discontinuing investigational product (IP) due to a clinically significant asthma exacerbation will then enter optional Part D of the study. During Part D, subjects receive open-label mepolizumab in addition to their standard of care therapy for the remainder of the study, through Part D up to 52-weeks post-randomization. An Exit Visit will be conducted 52 weeks after randomization in order to assess subject's efficacy parameters, immunogenicity status, and to conduct additional safety assessments. Eligible subjects will participate in the study ranging from 56 to192 weeks, depending on the duration of Part A (0 to 132 weeks) and Part B (4 to 8 weeks).


Condition or disease Intervention/treatment Phase
Asthma Biological: Mepolizumab 100mg Drug: Placebo Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 297 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Placebo Controlled, Parallel Group Study to Compare Cessation Versus Continuation of Long-term Mepolizumab Treatment in Patients With Severe Eosinophilic Asthma (201810)
Actual Study Start Date : January 7, 2016
Estimated Primary Completion Date : July 24, 2019
Estimated Study Completion Date : July 24, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Mepolizumab

Arm Intervention/treatment
Experimental: Arm Mepolizumab 100 mg
There will be 4 parts during the study. Part A will be Variable Open-Label Run-in (maximum up to 132 weeks). Part B- Fixed Open-Label Run-In (4 Weeks to 8 weeks). Part C will be randomized double-blind treatment period (Up to 52 weeks) and in case of clinically significant asthma exacerbation, optional open label switch Part D (Up to 52 weeks post randomization). Subjects will receive mepolizumab (100 mg SC) every 4 weeks throughout study
Biological: Mepolizumab 100mg
Mepolizumab is a fully humanised Immunoglobulin (IgG) antibody (IgG1, kappa) with human heavy and light chain frameworks. Mepolizumab will be provided as a lyophilised cake in sterile vials for individual use.

Placebo Comparator: Arm Placebo
There will be 4 parts during the study. Part A will be Variable Open-Label Run-in (maximum up to 132 weeks). Part B- Fixed Open-Label Run-In (4 Weeks to 8 weeks). Part C will be randomized double-blind treatment period (Up to 52 weeks) and in case of clinically significant asthma exacerbation, optional open label switch Part D (Up to 52 weeks post randomization). During Part A, B and D, subjects will receive open label mepolizumab (100 mg SC) every 4 weeks and during Part C, subjects will receive placebo SC every 4 weeks.
Biological: Mepolizumab 100mg
Mepolizumab is a fully humanised Immunoglobulin (IgG) antibody (IgG1, kappa) with human heavy and light chain frameworks. Mepolizumab will be provided as a lyophilised cake in sterile vials for individual use.

Drug: Placebo
The placebo will be 0.9% sodium chloride solution and will be provided by the study site.




Primary Outcome Measures :
  1. Time to first clinically significant exacerbation [ Time Frame: Up to 52 weeks ]
    Clinically significant exacerbations will be defined as worsening of asthma which requires use of systemic corticosteroids and/or hospitalisation and/or emergency department (ED) visits


Secondary Outcome Measures :
  1. Ratio to baseline in blood eosinophil count [ Time Frame: Baseline (Week 0) and up to Week 52 ]
    Blood eosinophil counts will be recorded as part of the standard haematological assessments at Baseline (Week 0), weeks 12, 24, 36 and 52 in Part C

  2. Time to a decrease in asthma control, defined as an increase from baseline in Asthma Control Questionnaire-5 (ACQ-5) score of >= 0.5 units [ Time Frame: Baseline (Week 0) and up to Week 52 ]
    The ACQ-5 is a five-item questionnaire, which has been developed as a measure of subject' asthma control that can be quickly and easily completed by the subject. The five questions enquire about the frequency and/or severity of symptoms over the previous week (nocturnal awakening on waking in the morning, activity limitation, and shortness of breath, wheeze). The response options for all these questions consist of a zero (no impairment/limitation) to six (total impairment/ limitation) scale. ACQ score will be collected at Baseline (Week 0) and at Weeks 12, 24, 36, 48 and 56.

  3. Time to first exacerbation requiring hospitalization or ED visit [ Time Frame: Up to 52 weeks ]
    Clinically significant exacerbations will be defined as worsening of asthma which requires use of systemic corticosteroids and/or hospitalisation and/or ED visits



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent, and an assent for subjects under 18 years of age, at Visit 0 (or Visit 1 if these Visits are conducted on the same day).
  • MEA115666 or 201312 Study Participation: Participation (through the Follow Up/Exit Visit or Early Withdrawal) in either study with documented evidence of at least 6 months of continuous mepolizumab treatment prior to Visit 1. Continuous treatment with mepolizumab is defined as no more than 2 consecutive missed doses (no treatment gaps of more than 12 weeks [84 days] between any two doses).
  • Current Anti-Asthma Therapy: Asthma is currently being treated with a controller 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: A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, > 45 years, in the absence of hormone replacement therapy.

OR Child bearing potential, has a negative pregnancy test at screening, and agrees to acceptable contraceptive methods approved in their local country, when used consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician) for the duration of the study and for 4 months after the last study drug administration.

A urine pregnancy test is required of all females of child-bearing potential at each scheduled study visit prior to the injection of study treatment, and at the Exit Visit, Early Withdrawal (EW) or Discontinuation of IP Visit.

  • 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.

Exclusion Criteria:

  • MEA115666 or 201312 IP Discontinuation: Subjects withdrawn from IP or withdrawn from study participation from either MEA115666 or 201312 for safety reasons.
  • Health Status: Clinically significant deterioration in health status at the completion of participation or EW from either the MEA115666 or 201312 trials which in the opinion of the investigator would make the subject unsuitable for participation in this study.
  • Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
  • Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to:

known ejection fraction of <30% OR severe heart failure meeting New York Heart Association Class IV classification OR hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III OR angina diagnosed less than 3 months prior to Visit 1 or at Visit 1.

  • 12-Lead Electrocardiogram (ECG): ECG which has a clinically significant abnormality observed at the Screening Visit as determined by the investigator. Subjects with the following abnormalities are excluded from study participation: QT interval corrected for heart rate by Fridericia's formula (QTcF) > 450 milliseconds (msec), or QTcF >480 msec for subjects with Bundle Branch Block.
  • Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (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.

  • Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody (other than XOLAIR®) to treat inflammatory disease within 5 half-lives of Visit 1.

XOLAIR is a registered trademark of Genentech USA, Inc. and Novartis Pharmaceuticals Corporation.

  • Adherence: Subjects who have known evidence of lack of adherence within studies MEA115666 or 201312 (less than 80%) to controller medications, scheduled study visits and/or ability to follow physician's recommendations.
  • Smoking status: Current smokers
  • Inability to read: In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02555371


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Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02555371     History of Changes
Other Study ID Numbers: 201810
2015-002361-32 ( EudraCT Number )
First Posted: September 21, 2015    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Severe eosinophilic asthma
mepolizumab
asthma exacerbation

Additional relevant MeSH terms:
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Asthma
Pulmonary Eosinophilia
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