Last updated: 05/14/2024 13:30:12
Efficacy and safety study of mepolizumab in subjects with severe hypereosinophilic syndrome (HES)
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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
Trial description: 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).
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Proportionof subjects who experience an HES flare during the 32-week study treatment period
Timeframe: Up to 33 weeks
Secondary outcomes:
Time to first HES flare
Timeframe: Up to 33 Weeks
Proportion of subjects who experience an HES flare during Week 20 through Week 32
Timeframe: From Week 20 until Week 32
Number of HES flares per subject per year
Timeframe: Baseline (randomization) and up to 33 Weeks
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
Timeframe: Baseline and up to Week 32
Interventions:
Enrollment:
108
Primary completion date:
2019-08-08
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Roufosse F, Kahn JE, Rothenberg M, Wardlaw AJ, Klion A, Yun Kirby S, Gilson M, Bentley J, Bradford E, Yancey S, Steinfeld J, Gleich G. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: a Phase III, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020;
DOI: 10.1016/j.jaci.2020.08.037
Reiter A, Lefevre G, Cid Xutgla M, Kwon N, Mavropoulou E, Yancey S, Steinfeld J.Association between baseline therapy and flare reduction in mepolizumab-treated patients with hypereosinophilic syndrome .Front Immunol.2022;13:840974
DOI: https://doi.org/10.3389/fimmu.2022.840974
PMID: NULL
Rothenberg M, Roufosse F, Faguer S, Gleich G, Steinfeld J, Yancey S, Mavropoulou E, Kwon N.Mepolizumab reduces hypereosinophilic syndrome flares irrespective of blood eosinophil count and IL-5 .J Allergy Clin Immunol Pract.2022;
DOI:10.1016/j.jaip.2022.04.037
PMID:35568330
Medical condition
Hypereosinophilic Syndrome
Product
mepolizumab
Collaborators
Not applicable
Study date(s)
March 2017 to August 2019
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
12+ years
Accepts healthy volunteers
No
- 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
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Blumenau, Santa Catarina, Brazil, 89030-101
Status
Study Complete
Location
GSK Investigational Site
Charleston, South Carolina, United States, 29425
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45229
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1028AAP
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
Status
Study Complete
Location
GSK Investigational Site
Kirchheim -Teck, Baden-Wuerttemberg, Germany, 73230
Status
Study Complete
Location
GSK Investigational Site
La Plata, Buenos Aires, Argentina, 1900
Status
Study Complete
Location
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68167
Status
Study Complete
Location
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, 7600
Status
Study Complete
Location
GSK Investigational Site
Mayfield Heights, Ohio, United States, 44124
Status
Study Complete
Location
GSK Investigational Site
New Haven, Connecticut, United States, 06520
Status
Study Complete
Location
GSK Investigational Site
Porto Alegre, Rio Grande Do Sul, Brazil, 90610000
Status
Study Complete
Location
GSK Investigational Site
Rochester, Minnesota, United States, 55905
Status
Study Complete
Location
GSK Investigational Site
Salt Lake City, Utah, United States, 84132
Status
Study Complete
Location
GSK Investigational Site
San Diego, California, United States, 92037-0641
Status
Study Complete
Location
GSK Investigational Site
Santo André - SP, São Paulo, Brazil, 09080-110
Status
Study Complete
Location
GSK Investigational Site
Sorocaba, São Paulo, Brazil, 18040-425
Status
Study Complete
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2019-08-08
Actual study completion date
2019-08-08
Plain language summaries
Summary of results in plain language
Available language(s): English, Dutch (Belgium), French, French (Belgium), German, Italian, Polish, Portuguese (Latin America), Romanian, Russian, Spanish, Spanish (Argentina), Spanish (Mexico)
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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