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AsthmaPhase 3NCT02555371

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

A Phase 3 study testing Mepolizumab 100mg in people with Asthma, run by GlaxoSmithKline at 73 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Asthma
What is being tested?
Mepolizumab 100mg
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
306 participants
Where
73 sitesin 14 countries
Study dates
7 Jan 2016to 24 Jul 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

73 sites in 14 countries.

73 sites in 14 countries

United States13 sites

  • GSK Investigational Site

    Albany, Georgia, 31707

  • GSK Investigational Site

    Baltimore, Maryland, 21224

  • GSK Investigational Site

    Denver, Colorado, 80206

  • GSK Investigational Site

    Durham, North Carolina, 27705

  • GSK Investigational Site

    Hershey, Pennsylvania, 17033

  • GSK Investigational Site

    Long Beach, California, 90808

  • GSK Investigational Site

    Murray, Utah, 84107

  • GSK Investigational Site

    Nashville, Tennessee, 37212

  • GSK Investigational Site

    New Haven, Connecticut, 6504

  • GSK Investigational Site

    Riverside, California, 92506

  • GSK Investigational Site

    Rochester, Minnesota, 55905

  • GSK Investigational Site

    Rochester, New York, 14642

  • GSK Investigational Site

    Winston-Salem, North Carolina, 27104

Other trials in United States

Japan9 sites

  • GSK Investigational Site

    Chiba, 296-8602

  • GSK Investigational Site

    Fukuoka, 802-0052

  • GSK Investigational Site

    Fukuoka, 811-1394

  • GSK Investigational Site

    Gunma, 370-0615

  • GSK Investigational Site

    Ibaraki, 319-1113

  • GSK Investigational Site

    Kanagawa, 252-0392

  • GSK Investigational Site

    Osaka, 596-8501

  • GSK Investigational Site

    Tokyo, 102-0083

  • GSK Investigational Site

    Tokyo, 103-0027

Other trials in Japan

South Korea7 sites

  • GSK Investigational Site

    Anyang-Si, Gyeonggi-do, 14068

  • GSK Investigational Site

    Bucheon-si, Gyeonggi-do, 14584

  • GSK Investigational Site

    Cheongju-si, Chungcheongbuk-do, 28644

  • GSK Investigational Site

    Gwangju, 61469

  • GSK Investigational Site

    Seoul, 06973

  • GSK Investigational Site

    Seoul, 120/752

  • GSK Investigational Site

    Suwon-si, Gyeonggi-do, 16499

Other trials in South Korea

Germany6 sites

  • GSK Investigational Site

    Berlin, 10367

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60596

  • GSK Investigational Site

    Gelnhausen, Hesse, 63571

  • GSK Investigational Site

    Lübeck, Schleswig-Holstein, 23552

  • GSK Investigational Site

    Magdeburg, 39120

  • GSK Investigational Site

    Neu-Isenburg, Hesse, 63263

Other trials in Germany

Argentina5 sites

  • GSK Investigational Site

    Buenos Aires, C1424BSF

  • GSK Investigational Site

    Buenos Aires, C1426ABP

  • GSK Investigational Site

    Mendoza, M5500CCG

  • GSK Investigational Site

    Rosario, Santa Fe Province, S2000DBS

  • GSK Investigational Site

    San Rafael, Mendoza Province, 5600

Other trials in Argentina

France5 sites

  • GSK Investigational Site

    Le Kremlin-Bicêtre, 94275

  • GSK Investigational Site

    Lille, 59037

  • GSK Investigational Site

    Marseille, 13915

  • GSK Investigational Site

    Montpellier, 34295

  • GSK Investigational Site

    Paris, 75877

Other trials in France

Russia5 sites

  • GSK Investigational Site

    Barnaul, 656 045

  • GSK Investigational Site

    Chelyabinsk, 454106

  • GSK Investigational Site

    Moscow, 123182

  • GSK Investigational Site

    Saint Petersburg, 194354

  • GSK Investigational Site

    Saint Petersburg, 194356

Other trials in Russia

Spain5 sites

  • GSK Investigational Site

    Alicante, 03004

  • GSK Investigational Site

    Barcelona, 08025

  • GSK Investigational Site

    Barcelona, 08036

  • GSK Investigational Site

    Pozuelo de Alarcón/Madrid, 28223

  • GSK Investigational Site

    Sabadell (Barcelona), 08208

Other trials in Spain

Canada4 sites

  • GSK Investigational Site

    Montreal, Quebec, H2X 3E4

  • GSK Investigational Site

    Montreal, Quebec, H4J 1C5

  • GSK Investigational Site

    Québec, G1V 4G5

  • GSK Investigational Site

    Saint-Charles-Borromée, Quebec, J6E 2B4

Other trials in Canada

Poland4 sites

  • GSK Investigational Site

    Bialystok, 15-044

  • GSK Investigational Site

    Krakow, 30-033

  • GSK Investigational Site

    Lodz, 90-153

  • GSK Investigational Site

    Wroclaw, 54-239

Other trials in Poland

Ukraine4 sites

  • GSK Investigational Site

    Dnipropetrovsk, 49074

  • GSK Investigational Site

    Kharkiv, 61124

  • GSK Investigational Site

    Mykolayiv, 54003

  • GSK Investigational Site

    Vinnytsia, 21018

Other trials in Ukraine

Australia2 sites

  • GSK Investigational Site

    Nedlands, Western Australia, 6009

  • GSK Investigational Site

    New Lambton, New South Wales, 2305

Other trials in Australia

Netherlands2 sites

  • GSK Investigational Site

    Amsterdam, 1105 AZ

  • GSK Investigational Site

    Leeuwarden, 8934 AD

Other trials in Netherlands

Romania2 sites

  • GSK Investigational Site

    Bucharest, 050159

  • GSK Investigational Site

    Iași, 700115

Other trials in Romania

About this study

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)

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).

Conditions
Asthma
Being tested
Mepolizumab 100mg, Placebo
Keywords
Severe eosinophilic asthma, mepolizumab, asthma exacerbation
Medical subject headings
Asthma, Pulmonary Eosinophilia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mepolizumab 100mgBiological

    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.

  • PlaceboDrug

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

Study groups in NCT02555371
Study groupRoleWhat they receive
Arm Mepolizumab 100 mgExperimentalThere 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
Receives: Biological: Mepolizumab 100mg
Arm PlaceboPlacebo comparatorThere 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.
Receives: Biological: Mepolizumab 100mg; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With First Clinically Significant Exacerbation in Part C

    Clinically significant exacerbation was defined as worsening of asthma which requires use of systemic corticosteroids (e.g., prednisone) for at least 3 days or a single intramuscular (IM) corticosteroid dose and/or hospitalization and/or emergency department (ED) visits. For participants on maintenance systemic corticosteroids, at least double the existing maintenance dose for at least 3 days is required. Percentage of participants with clinically significant exacerbation over time during the on-treatment period of Part C and 95% confidence interval were estimated using Kaplan-Meier estimates. Intent-to-Treat Population includes all randomized participants who received at least one dose of double-blind study medication within Part C.

    Measured: Weeks 12, 24, 36 and 52

Secondary outcomes (3)

  1. Ratio to Baseline in Blood Eosinophil Count in Part C

    Blood samples were collected at specific time points to measure blood eosinophils level. Baseline was defined as the latest available assessment prior to first dose of double-blind treatment within Part C. Ratio to Baseline is defined as visit value divided by Baseline value and was analyzed using Mixed Model Repeated Measures with covariates of Baseline, region, exacerbations in the year prior to randomization (as an ordinal variable), Baseline maintenance oral corticosteroids (OCS) therapy (OCS versus no OCS), treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group. The log transformation was applied to blood eosinophil counts prior to analysis. If a blood eosinophil count of zero was reported, a small value was added prior to log transforming the data. The dispersion measure used was log standard error.

    Measured: Baseline and Weeks 12, 24, 36 and 52

  2. Percentage of Participants With 0.5 Point or More Increase in Asthma Control Questionnaire (ACQ)-5 Score From Baseline in Part C

    The ACQ-5 is a five-item, self-completed questionnaire. Five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response ranges from zero (no impairment/limitation) to six (total impairment/ limitation) scale. Increase in score of >= 0.5 units from Baseline indicates decrease in asthma control. Baseline is the latest available assessment prior to first dose of double-blind treatment within Part C. Percentage of participants with a 0.5 point or more increase in ACQ-5 score from Baseline over time during the on-treatment period of Part C and its 95% confidence interval were estimated using Kaplan-Meier estimates.

    Measured: Baseline and Weeks 12, 24, 36 and 52

  3. Percentage of Participants With Time to First Exacerbation Requiring Hospitalization or ED Visit in Part C

    Exacerbations of asthma requiring hospitalization or ED visit were assessed. The analysis was performed from Cox Proportional Hazards Model with covariates of treatment group, region, exacerbations in the year prior to randomization (as an ordinal variable) and Baseline maintenance OCS therapy (OCS versus no OCS). Percentage of participants with an exacerbation over time and its 95% confidence intervals were estimated using Kaplan-Meier estimates

    Measured: Weeks 12, 24, 36 and 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2015 (estimated)
  2. Study start7 Jan 2016
  3. Primary completion24 Jul 2019
  4. Study completion24 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
306 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02555371
Sponsor's protocol ID
201810
Other IDs
2015-002361-32, 2015
Status last verified
Jan 2020
First submitted
17 Sep 2015
Last updated
5 Feb 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Expanded access
Available

Publications

  • Moore WC, Kornmann O, Humbert M, Poirier C, Bel EH, Kaneko N, Smith SG, Martin N, Gilson MJ, Price RG, Bradford ES, Liu MC. Stopping versus continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study). Eur Respir J. 2022 Jan 6;59(1):2100396. doi: 10.1183/13993003.00396-2021. Print 2022 Jan.

    PubMed 34172470

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Mepolizumab 100mg in people with Asthma, run by GlaxoSmithKline at 73 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 73 sites in United States, Japan, South Korea, Germany, Argentina and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With First Clinically Significant Exacerbation in Part C (time frame: Weeks 12, 24, 36 and 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02555371, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.

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