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Trial record 2 of 513 for:    HES

Efficacy and Safety Study of Mepolizumab in Subjects With Severe Hypereosinophilic Syndrome (HES)

This study is currently recruiting participants.
See Contacts and Locations
Verified September 2017 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02836496
First received: July 14, 2016
Last updated: September 21, 2017
Last verified: September 2017
  Purpose
Mepolizumab is a humanized monoclonal antibody. In conditions where eosinophilia is considered to play an important part in the pathology, including eosinophilic asthma, HES, and eosinophilic granulomatosis with polyangiitis, a consistent reduction in blood eosinophil counts is observed in association with mepolizumab administration, with concomitant clinical improvement. This is a 32-week treatment period, randomized, double-blind, placebo-controlled, parallel group, multicentre study of mepolizumab in adolescent and adult subjects with severe HES receiving standard of care (SoC) therapy. This study will demonstrate the efficacy of mepolizumab compared with placebo based on maintenance of control of HES symptoms during the treatment period. The study will comprise of a screening period of up to approximately 4 weeks followed by a 32-Week study treatment period (subjects will be randomized 1:1 to placebo or mepolizumab) and up to 8-week additional follow-up period (12 weeks after the last dose of study treatment).

Condition Intervention Phase
Hypereosinophilic Syndrome Drug: Mepolizumab 300 mg Drug: Placebo matching mepolizumab Drug: Active OCS capsules (5 mg prednisolone or prednisone) Drug: Placebo matching OCS capsules Phase 3

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Study 200622: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Mepolizumab in the Treatment of Adolescent and Adult Subjects With Severe Hypereosinophilic Syndrome

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Proportionof subjects who experience an HES flare during the 32-week study treatment period [ Time Frame: Up to 33 weeks ]
    HES flare is defined as either an HES-related clinical manifestation based on a physician-documented change in clinical signs or symptoms when maintenance oral corticosteroids (OCS) dose will be increased by at least 10 milligram [mg]/day for 5 days or any cytotoxic and/or immunosuppressive HES therapy increase or addition will be needed or receipt of two or more courses of blinded active OCS during the treatment period.


Secondary Outcome Measures:
  • Time to first HES flare [ Time Frame: Up to 33 Weeks ]
    The time to first HES flare will be calculated from the date of randomization and the start date of the HES flare.

  • Proportion of subjects who experience an HES flare during Week 20 through Week 32 [ Time Frame: From Week 20 until Week 32 ]
    An HES flare during Week 20 through Week 32 will be defined as an HES flare starting or ongoing on or after the date of the Week 20 visit up to and including the date of the Week 32 visit.

  • Number of HES flares per subject per year [ Time Frame: Baseline (randomization) and up to 33 Weeks ]
    The rate of HES flares will be calculated for each subject as the number of observed HES flares divided by the time (expressed in years) between randomization and either the week 32 visit date if available, or otherwise the study withdrawal date. Start date of an HES flare must be at least 14 days apart from the resolution date of the preceding HES flare to be considered as a separate episode of HES flare.

  • Change from baseline in fatigue severity based on Brief Fatigue Inventory (BFI) item 3 (worst level of fatigue during past 24 hours) at Week 32 [ Time Frame: Baseline and up to Week 32 ]
    BFI item 3 assesses the worst level of fatigue during past 24 hours using a numeric rating scale anchored with 0 (no fatigue/interference) and 10 (as bad as you can imagine/completely interferes).


Estimated Enrollment: 120
Actual Study Start Date: March 7, 2017
Estimated Study Completion Date: February 25, 2019
Estimated Primary Completion Date: February 25, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mepolizumab
Enrolled subjects will receive either mepolizumab 300 mg or placebo subcutaneous (SC) every 4 weeks while continuing their HES therapy.
Drug: Mepolizumab 300 mg
Mepolizumab is available as lyophilized powder for injection reconstituted with Sterile Water for Injection, just prior to use.
Drug: Active OCS capsules (5 mg prednisolone or prednisone)
All subjects will be provided with 2 bottles of blinded OCS capsules, one containing 5mg OCS capsules (active OCS treatment) and a second one containing matching placebo capsules (placebo OCS treatment). These will be dispensed to each subject at each scheduled clinic visit and as needed. Subjects with an increase in blood eosinophils above the pre-specified threshold will be instructed to start blinded OCS treatment from one of the bottles provided (active treatment) unless the subject's HES therapy has already been increased due to a symptom flare within the past 2 weeks.
Drug: Placebo matching OCS capsules
All subjects will be provided with 2 bottles of blinded OCS capsules, one containing 5mg OCS capsules (active OCS treatment) and a second one containing matching placebo capsules (placebo OCS treatment). These will be dispensed to each subject at each scheduled clinic visit and as needed.A subject who does not reach the pre-specified blood eosinophil threshold with a similar blood draw date will be selected to initiate a placebo OCS treatment in a blinded manner, unless the subject's HES therapy has already been increased due to a symptom flare within the past 2 weeks.
Placebo Comparator: Placebo
Enrolled subjects will receive either mepolizumab 300 mg or placebo SC every 4 weeks while continuing their HES therapy.
Drug: Placebo matching mepolizumab
Placebo is available as 0.9% sodium chloride solution
Drug: Active OCS capsules (5 mg prednisolone or prednisone)
All subjects will be provided with 2 bottles of blinded OCS capsules, one containing 5mg OCS capsules (active OCS treatment) and a second one containing matching placebo capsules (placebo OCS treatment). These will be dispensed to each subject at each scheduled clinic visit and as needed. Subjects with an increase in blood eosinophils above the pre-specified threshold will be instructed to start blinded OCS treatment from one of the bottles provided (active treatment) unless the subject's HES therapy has already been increased due to a symptom flare within the past 2 weeks.
Drug: Placebo matching OCS capsules
All subjects will be provided with 2 bottles of blinded OCS capsules, one containing 5mg OCS capsules (active OCS treatment) and a second one containing matching placebo capsules (placebo OCS treatment). These will be dispensed to each subject at each scheduled clinic visit and as needed.A subject who does not reach the pre-specified blood eosinophil threshold with a similar blood draw date will be selected to initiate a placebo OCS treatment in a blinded manner, unless the subject's HES therapy has already been increased due to a symptom flare within the past 2 weeks.

  Eligibility

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

Inclusion Criteria:

  • Capable of giving signed informed consent/assent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol
  • Twelve years of age or older, at the time of signing the informed consent/assent
  • Subjects who have been diagnosed with HES for at least 6 months at randomization
  • A history of two or more HES flares within the past 12 months prior to screening. Historical HES flares are defined as documented HES-related worsening of clinical symptoms or blood eosinophil counts requiring an escalation in therapy. At least one HES flare within the past 12 months must not be related to a decrease in HES therapy during the 4 weeks prior to the flare.
  • Subjects must have blood eosinophil count >=1000 cells/µL present in the sample collected during screening (within 4 weeks prior to randomization).
  • Subjects must be on a stable dose of HES therapy for the 4 weeks prior to randomization. HES therapy includes but is not limited to oral corticosteroid, immunosuppressive, and cytotoxic therapy.
  • Male or female. A female subject is eligible to participate if she is not pregnant, not lactating, and either non-reproductive potential or reproductive potential and agree to use a highly effective method to avoid pregnancy from 30 days prior to the first dose of study medication and until 4 months after the last dose of study treatment.

Exclusion Criteria:

  • Life-threatening HES or life-threatening HES co-morbidities: Imminently life-threatening HES disease severity such that the likelihood of death is high unless the course of the disease is interrupted within 12 weeks prior to randomization.
  • Subjects who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological, respiratory or any other system abnormalities that are not associated with HES and are uncontrolled with standard treatment.
  • Eosinophilia of unknown clinical significance
  • Twelve-lead electrocardiogram (ECG) finding: QT interval corrected for heart rate (QTc) > 450 msec or QTc > 480 msec in subjects with bundle branch block or an abnormal ECG finding from the 12-lead ECG conducted at Visit 1 if considered to be clinically significant and would impact the subject's participation during the study based on the evaluation of the Investigator.
  • Subjects with documented history of any clinically significant cardiac damage prior to screening that, in the opinion of the investigator, would impact the subject's participation during the study.
  • Liver abnormality/disease - Alanine transaminase (ALT) >2.5x upper limit of normal (ULN) or ALT>5xULN if documented HES with liver manifestations, or bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent), or current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis.

NOTE: Chronic stable hepatitis B and C (e.g., presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria.

  • Clinical diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA)
  • Subjects with a history of or current lymphoma, or subjects with current malignancy or previous history of cancer in remission for less than 12 months prior to randomization. Subjects that had localized carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded.
  • FIP1 like 1-platelet derived growth factor receptor (FIP1L1-PDGFR) Status: Subjects who test positive for the FIP1L1-PDGFR fusion tyrosine kinase gene translocation.
  • Subjects with chronic or ongoing active infections requiring systemic treatment, as well as subjects who have experienced clinically significant infections due to viruses, bacteria, and fungi within 4 weeks prior to randomization or subjects with a pre-existing helminthes infestation within 6 months prior to randomization
  • Subjects with a known human immunodeficiency virus (e.g., HIV), other than that explained by the use of OCS or other therapy taken for HES.
  • Other laboratory abnormalities: Evidence of clinically significant abnormality in the hematological, biochemical or urinalysis screen from the sample collected at screening, that could put the subject's safety at risk by participating in the study, as judged by the investigator
  • Subjects who have previously received mepolizumab in the 4 months prior to randomization
  • Subjects receiving intravenous or subcutaneous corticosteroids in the 4-week period prior to randomization or any other monoclonal antibodies within 30 days or 5 half-lives, whichever is longer, of randomization
  • Subjects who have received treatment with an investigational agent (biologic or non-biologic) within the past 30 days or 5 drug half-lives whichever is longer, prior to randomization or subjects who are currently participating in any other interventional clinical study
  • Subjects who are not responsive to oral corticosteroid based on clinical response or blood eosinophil counts
  • Subjects with any history of hypersensitivity to any monoclonal antibody (including mepolizumab) or any steroid or steroid-containing product
  • Subjects with a known or suspected history of alcohol or substance abuse at screening which in the opinion of the investigator could interfere with the subject's proper completion of the protocol requirement.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02836496

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
United States, Minnesota
GSK Investigational Site Recruiting
Rochester, Minnesota, United States, 55905
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United States, Utah
GSK Investigational Site Recruiting
Salt Lake City, Utah, United States, 84132
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Belgium
GSK Investigational Site Recruiting
Bruxelles, Belgium, 1070
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Leuven, Belgium, 3000
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
France
GSK Investigational Site Not yet recruiting
Lille cedex, France, 59037
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Nantes Cedex 1, France, 44093
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Suresnes, France, 92150
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Toulouse Cedex 9, France, 31059
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Germany
GSK Investigational Site Recruiting
Kirchheim -Teck, Baden-Wuerttemberg, Germany, 73230
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
Mannheim, Baden-Wuerttemberg, Germany, 68167
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
Muenchen, Bayern, Germany, 80802
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Hannover, Niedersachsen, Germany, 30625
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Mexico
GSK Investigational Site Recruiting
Guadalajara, Jalisco, Mexico, 44100
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Villahermosa, Tabasco, Mexico, 86035
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Romania
GSK Investigational Site Not yet recruiting
Bucharest, Romania, 010306
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Russian Federation
GSK Investigational Site Not yet recruiting
Saint-Petersburg, Russian Federation, 197341
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Spain
GSK Investigational Site Recruiting
Barcelona, Spain, 08035
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Barcelona, Spain, 08036
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
Málaga, Spain, 29010
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
Pozuelo (Madrid), Spain, 28223
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
Salamanca, Spain, 37007
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Valencia, Spain, 46026
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United Kingdom
GSK Investigational Site Recruiting
Leicester, United Kingdom, LE3 9QP
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02836496     History of Changes
Other Study ID Numbers: 200622
Study First Received: July 14, 2016
Last Updated: September 21, 2017

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

Keywords provided by GlaxoSmithKline:
Safety
Mepolizumab
Hypereosinophilic syndrome
HES flare
Efficacy

Additional relevant MeSH terms:
Hypereosinophilic Syndrome
Syndrome
Disease
Pathologic Processes
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Prednisone
Prednisolone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 25, 2017