Hypereosinophilic SyndromePhase 3NCT02836496
Efficacy and Safety Study of Mepolizumab in Subjects With Severe Hypereosinophilic Syndrome (HES)
A Phase 3 study testing Mepolizumab 300 mg and Active OCS capsules (5 mg prednisolone or prednisone) in people with Hypereosinophilic Syndrome, run by GlaxoSmithKline at 43 sites in 13 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Hypereosinophilic Syndrome
- What is being tested?
- Mepolizumab 300 mg and Active OCS capsules (5 mg prednisolone or prednisone)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 43 sitesin 13 countries
- Study dates
- 7 Mar 2017to 8 Aug 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
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
Trial locations and contacts
43 sites in 13 countries.
43 sites in 13 countries
United States7 sites
GSK Investigational Site
Charleston, South Carolina, 29425
GSK Investigational Site
Cincinnati, Ohio, 45229
GSK Investigational Site
Mayfield Heights, Ohio, 44124
GSK Investigational Site
New Haven, Connecticut, 06520
GSK Investigational Site
Rochester, Minnesota, 55905
GSK Investigational Site
Salt Lake City, Utah, 84132
GSK Investigational Site
San Diego, California, 92037-0641
Germany5 sites
GSK Investigational Site
Fulda, Hesse, 36043
GSK Investigational Site
Hanover, Lower Saxony, 30625
GSK Investigational Site
Kirchheim -Teck, Baden-Wurttemberg, 73230
GSK Investigational Site
Mannheim, Baden-Wurttemberg, 68167
GSK Investigational Site
Munich, Bavaria, 80802
Argentina4 sites
GSK Investigational Site
Buenos Aires, C1425BEN
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, C1028AAP
GSK Investigational Site
La Plata, Buenos Aires
GSK Investigational Site
Mar del Plata, Buenos Aires, 7600
Brazil4 sites
GSK Investigational Site
Blumenau, Santa Catarina, 89030-101
GSK Investigational Site
Porto Alegre, Rio Grande do Sul, 90610000
GSK Investigational Site
Santo André - SP, São Paulo, 09080-110
GSK Investigational Site
Sorocaba, São Paulo, 18040-425
France4 sites
GSK Investigational Site
Lille, 59037
GSK Investigational Site
Nantes, 44093
GSK Investigational Site
Suresnes, 92150
GSK Investigational Site
Toulouse, 31059
Mexico3 sites
GSK Investigational Site
Guadalajara, Jalisco, 44100
GSK Investigational Site
Monterrey, Nuevo León, 64710
GSK Investigational Site
Villahermosa, Tabasco, 86035
Romania3 sites
GSK Investigational Site
Bucharest, 010306
GSK Investigational Site
Cluj-Napoca, 400124
GSK Investigational Site
Târgu Mureş, 540327
Russia3 sites
GSK Investigational Site
Moscow, 125167
GSK Investigational Site
Saint Petersburg, 193024
GSK Investigational Site
Saint Petersburg, 197341
Spain3 sites
GSK Investigational Site
Barcelona, 08035
GSK Investigational Site
Barcelona, 08036
GSK Investigational Site
Valencia, 46026
Belgium2 sites
GSK Investigational Site
Brussels, 1070
GSK Investigational Site
Leuven, 3000
Italy2 sites
GSK Investigational Site
Florence, Tuscany, 50134
GSK Investigational Site
Naples, Campania, 80131
Poland2 sites
GSK Investigational Site
Krakow, 31-066
GSK Investigational Site
Lodz, 90-153
About this study
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
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).
- Conditions
- Hypereosinophilic Syndrome
- Being tested
- Mepolizumab 300 mg, Placebo matching mepolizumab, Active OCS capsules (5 mg prednisolone or prednisone), Placebo matching OCS capsules
- Keywords
- Safety, Mepolizumab, Hypereosinophilic syndrome, HES flare, Efficacy
- Medical subject headings
- Hypereosinophilic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mepolizumab 300 mgDrug
Mepolizumab is available as lyophilized powder for injection reconstituted with Sterile Water for Injection, just prior to use.
Placebo matching mepolizumabDrug
Placebo is available as 0.9% sodium chloride solution
Active OCS capsules (5 mg prednisolone or prednisone)Drug
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.
Placebo matching OCS capsulesDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Mepolizumab | Experimental | Enrolled subjects will receive either mepolizumab 300 mg or placebo subcutaneous (SC) every 4 weeks while continuing their HES therapy. Receives: Drug: Mepolizumab 300 mg; Drug: Active OCS capsules (5 mg prednisolone or prednisone); Drug: Placebo matching OCS capsules |
| Placebo | Placebo comparator | Enrolled subjects will receive either mepolizumab 300 mg or placebo SC every 4 weeks while continuing their HES therapy. Receives: Drug: Placebo matching mepolizumab; Drug: Active OCS capsules (5 mg prednisolone or prednisone); Drug: Placebo matching OCS capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Experienced an HES Flare or Who Withdrew From the Study During the 32-Week Study Treatment Period
Percentage of participants who experienced >=1 HES flare during the 32-Week treatment period or who withdrew from the study has been presented. A HES flare is defined as a HES related clinical manifestation based on a physician-documented change in clinical signs or symptoms which resulted in need for an increase in the maintenance Oral Corticosteroid (OCS) dose by at least 10 mg per day for 5 days or an increase in or addition of any cytotoxic or immunosuppressive HES therapy. HES flare is also defined as receipt of two or more courses of blinded active OCS during the treatment period. Intent-to-treat (ITT) Population comprises of all randomized participants. This population was based on the treatment to which the participants were randomized. Any participant who received a treatment randomization number were considered to be randomized.
Measured: Up to Week 32
Secondary outcomes (4)
Percentage of Participants Who Experienced a HES Flare or Who Withdrew From the Study During Week 20 Through Week 32
HES flare during Week 20 through Week 32 was defined as a 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. Percentage of participants who experienced >=1 HES flare during Week 20 through Week 32 or who withdrew from the study has been presented.
Measured: Week 20 to Week 32
Time to First HES Flare
The time to first HES flare was calculated as (onset date of first HES flare minus date of first dose of study treatment) plus 1. Probability of first flare (by week 4, 8, 12, 16, 20, 24, 28, and 32) and corresponding 95% CI have been presented, calculated using the Kaplan-Meier method.
Measured: Weeks 4, 8, 12, 16, 20, 24, 28 and 32
Number of HES Flares Per Participant Per Year
The rate of HES flares for each participant was calculated 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 the study withdrawal date. Negative binomial generalized linear model including Baseline OCS dose, region, treatment and observed time (offset variable). Wilcoxon test stratified by Baseline OCS (0-<=20mg/day, >20mg/day prednisone or equivalent) and region. Adjusted mean and 95% CI rate/year has been presented.
Measured: Up to Week 32
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category
The change from Baseline in fatigue severity (worst level of fatigue during past 24 hours) at Week 32 was calculated using the mean of the 7 daily assessments of BFI item 3 up to and including the date of the Week 32 visit as the Week 32 assessment, and the mean of the 7 daily assessments of BFI item 3 up to but not including the date of first dose of study treatment as the Baseline assessment. Wilcoxon Rank Sum test stratified by Baseline fatigue severity ("severe" defined as BFI item 3>=7 and "not severe" defined as BFI item 3<7), Baseline OCS (0-<=20mg/day and >20mg/day prednisone or equivalent) and region. Participants with missing change from Baseline at Week 32 were included in the worst category (>=4 point increase).
Measured: Baseline (Week 0) and at Week 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2016 (estimated)
- Study start7 Mar 2017
- Primary completion8 Aug 2019
- Study completion8 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Hypereosinophilic SyndromeStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02836496
- Sponsor's protocol ID
- 200622
- Status last verified
- Feb 2020
- First submitted
- 14 Jul 2016
- Last updated
- 21 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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
Roufosse F, Butterfield J, Steinfeld J, Bentley JH, von Maltzahn R, Kwon N, Nelsen L. Mepolizumab therapy improves the most bothersome symptoms in patients with hypereosinophilic syndrome. Front Med (Lausanne). 2023 Mar 29;10:1035250. doi: 10.3389/fmed.2023.1035250. eCollection 2023.
PubMed 37064032Pane F, Lefevre G, Kwon N, Bentley JH, Yancey SW, Steinfeld J. Characterization of disease flares and impact of mepolizumab in patients with hypereosinophilic syndrome. Front Immunol. 2022 Aug 26;13:935996. doi: 10.3389/fimmu.2022.935996. eCollection 2022.
PubMed 36091012Rothenberg ME, Roufosse F, Faguer S, Gleich GJ, Steinfeld J, Yancey SW, Mavropoulou E, Kwon N; HES Mepolizumab Study Group. Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5. J Allergy Clin Immunol Pract. 2022 Sep;10(9):2367-2374.e3. doi: 10.1016/j.jaip.2022.04.037. Epub 2022 May 12.
PubMed 35568330Reiter A, Lefevre G, Cid MC, Kwon N, Mavropolou E, Yancey SW, Steinfeld J. Association Between Baseline Therapy and Flare Reduction in Mepolizumab-Treated Patients With Hypereosinophilic Syndrome. Front Immunol. 2022 Apr 13;13:840974. doi: 10.3389/fimmu.2022.840974. eCollection 2022.
PubMed 35493455Gleich GJ, Roufosse F, Chupp G, Faguer S, Walz B, Reiter A, Yancey SW, Bentley JH, Steinfeld J; HES Mepolizumab Study Group. Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4431-4440.e1. doi: 10.1016/j.jaip.2021.07.050. Epub 2021 Aug 10.
PubMed 34389506Roufosse F, Kahn JE, Rothenberg ME, Wardlaw AJ, Klion AD, Kirby SY, Gilson MJ, Bentley JH, Bradford ES, Yancey SW, Steinfeld J, Gleich GJ; HES Mepolizumab study group. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020 Dec;146(6):1397-1405. doi: 10.1016/j.jaci.2020.08.037. Epub 2020 Sep 18.
PubMed 32956756
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02836496
- Acronym / sponsor ID
- 200622
- Conditions
- Hypereosinophilic Syndrome
- Keywords
- Safety, Mepolizumab, Hypereosinophilic syndrome, HES flare, Efficacy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 7 Mar 2017 (actual)
- Primary completion
- 8 Aug 2019 (actual)
- Study completion
- 8 Aug 2019 (actual)
- First posted
- 19 Jul 2016 (estimated)
- Results
- Posted 21 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mepolizumab | Experimental | Drug: Mepolizumab 300 mg, Drug: Active OCS capsules (5 mg prednisolone or prednisone), Drug: Placebo matching OCS capsulesEnrolled subjects will receive either mepolizumab 300 mg or placebo subcutaneous (SC) every 4 weeks while continuing their HES therapy. |
| Placebo | Placebo comparator | Drug: Placebo matching mepolizumab, Drug: Active OCS capsules (5 mg prednisolone or prednisone), Drug: Placebo matching OCS capsulesEnrolled subjects will receive either mepolizumab 300 mg or placebo SC every 4 weeks while continuing their HES therapy. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mepolizumab 300 mgMepolizumab is available as lyophilized powder for injection reconstituted with Sterile Water for Injection, just prior to use. | Drug | Mepolizumab |
| Placebo matching mepolizumabPlacebo is available as 0.9% sodium chloride solution | Drug | Placebo |
| 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 | Mepolizumab, Placebo |
| Placebo matching OCS capsulesAll 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. | Drug | Mepolizumab, Placebo |
Primary outcome
Percentage of Participants Who Experienced an HES Flare or Who Withdrew From the Study During the 32-Week Study Treatment Period
Time frame: Up to Week 32
Percentage of participants who experienced >=1 HES flare during the 32-Week treatment period or who withdrew from the study has been presented. A HES flare is defined as a HES related clinical manifestation based on a physician-documented change in clinical signs or symptoms which resulted in need for an increase in the maintenance Oral Corticosteroid (OCS) dose by at least 10 mg per day for 5 days or an increase in or addition of any cytotoxic or immunosuppressive HES therapy. HES flare is also defined as receipt of two or more courses of blinded active OCS during the treatment period. Intent-to-treat (ITT) Population comprises of all randomized participants. This population was based on the treatment to which the participants were randomized. Any participant who received a treatment randomization number were considered to be randomized.
4 secondary outcomes
Percentage of Participants Who Experienced a HES Flare or Who Withdrew From the Study During Week 20 Through Week 32
Time frame: Week 20 to Week 32
Time to First HES Flare
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28 and 32
Number of HES Flares Per Participant Per Year
Time frame: Up to Week 32
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category
Time frame: Baseline (Week 0) and at Week 32
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37064032Roufosse F, Butterfield J, Steinfeld J, Bentley JH, von Maltzahn R, Kwon N, Nelsen L. Mepolizumab therapy improves the most bothersome symptoms in patients with hypereosinophilic syndrome. Front Med (Lausanne). 2023 Mar 29;10:1035250. doi: 10.3389/fmed.2023.1035250. eCollection 2023.
- Derived from this study: PubMed 36091012Pane F, Lefevre G, Kwon N, Bentley JH, Yancey SW, Steinfeld J. Characterization of disease flares and impact of mepolizumab in patients with hypereosinophilic syndrome. Front Immunol. 2022 Aug 26;13:935996. doi: 10.3389/fimmu.2022.935996. eCollection 2022.
- Derived from this study: PubMed 35568330Rothenberg ME, Roufosse F, Faguer S, Gleich GJ, Steinfeld J, Yancey SW, Mavropoulou E, Kwon N; HES Mepolizumab Study Group. Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5. J Allergy Clin Immunol Pract. 2022 Sep;10(9):2367-2374.e3. doi: 10.1016/j.jaip.2022.04.037. Epub 2022 May 12.
- Derived from this study: PubMed 35493455Reiter A, Lefevre G, Cid MC, Kwon N, Mavropolou E, Yancey SW, Steinfeld J. Association Between Baseline Therapy and Flare Reduction in Mepolizumab-Treated Patients With Hypereosinophilic Syndrome. Front Immunol. 2022 Apr 13;13:840974. doi: 10.3389/fimmu.2022.840974. eCollection 2022.
- Derived from this study: PubMed 34389506Gleich GJ, Roufosse F, Chupp G, Faguer S, Walz B, Reiter A, Yancey SW, Bentley JH, Steinfeld J; HES Mepolizumab Study Group. Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4431-4440.e1. doi: 10.1016/j.jaip.2021.07.050. Epub 2021 Aug 10.
- Derived from this study: PubMed 32956756Roufosse F, Kahn JE, Rothenberg ME, Wardlaw AJ, Klion AD, Kirby SY, Gilson MJ, Bentley JH, Bradford ES, Yancey SW, Steinfeld J, Gleich GJ; HES Mepolizumab study group. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020 Dec;146(6):1397-1405. doi: 10.1016/j.jaci.2020.08.037. Epub 2020 Sep 18.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
43 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mepolizumab 300 mg and Active OCS capsules (5 mg prednisolone or prednisone) in people with Hypereosinophilic Syndrome, run by GlaxoSmithKline at 43 sites in 13 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 19 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 21 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 43 sites in United States, Germany, Argentina, Brazil, France and 8 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 21 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 Who Experienced an HES Flare or Who Withdrew From the Study During the 32-Week Study Treatment Period (time frame: Up to Week 32). 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 NCT02836496, which also lists 6 linked publications.
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 21 Feb 2020.