Clinical trial NCT03306043: A Multi-center, Open-label Extension, Safety Study of Mepolizumab in Subjects With Hypereosinophilic Syndrome (HES) From Study 200622
Official title: A Multi-centre, Open-label Extension, Safety Study to Describe the Long-term Clinical Experience of Mepolizumab in Participants With Hypereosinophilic Syndrome (HES) From Study 200622
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypereosinophilic Syndrome
Keywords: hypereosinophilic syndrome
hypereosinophilic syndrome flare
open-label extension study
Mepolizumab
SB240563
Long-term safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-10-10
Enrollment: 102
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A single group of subjects will receive 300 mg SC mepolizumab every 4 Weeks.
Primary purpose: TREATMENT

Brief summary: This is an open-label extension study to Study 200622.In this study subjects from Study 200622 will be continued on 4-weekly dosing with open-label mepolizumab 300 milligram (mg) subcutaneously (SC) for an additional 20 Weeks after completing the 32 Week study assessments post-randomization, while they continue with their background HES therapy per standard of care (SoC). Subjects from study 200622 will participate in this extension study if they had completed the 32-Week treatment period in study 200622 or if they were withdrawn from the study pre-maturely, but were continued in the study per protocol until 32 Weeks from randomization. Data from this study (205203) and 200622 will be combined to provide up to 52-Week exposure data to further characterize the long-term safety profile of mepolizumab and provide additional data on the clinical benefit in HES subjects beyond 32 Weeks. The duration of the study participation will be 20 Weeks for subjects who continue with mepolizumab treatment via MHE104317/MHE112562 after this open-label extension study; and 28 Weeks for subjects who do not continue with MHE104317/MHE112562.


Eligibility criteria: Inclusion Criteria:

* Age 12 years and older subjects who were enrolled in Study 200622.
* To be considered for Study 205203, subjects from study 200622 must have completed 32-Week treatment period in the study or if the subject was withdrawn from study treatment prematurely during the 200622 study, but continued in the study per protocol (including HES flare-related assessments) until 32 Weeks from randomization.
* Male or female subjects. Female subjects must be either not a woman of childbearing potential (WOCBP) or WOCBP who agrees to follow the contraceptive guidance at least 30 days prior to the first dose of study treatment and until 16 weeks after the last dose of study treatment.
* The treating physician must confirm a positive benefit/risk ratio. The anticipated clinical benefit from mepolizumab must outweigh any potential safety or tolerability risk in Study 205203.
* Capable of giving signed informed consent.

Exclusion Criteria:

* Subjects with any history of hypersensitivity to any monoclonal antibody (including mepolizumab).
* Subjects with current malignancy or malignancy that developed during Study 200622.
* Subjects who is pregnant or breastfeeding.
* Subjects who has other clinically significant medical conditions uncontrolled with SoC therapy not associated with HES, example (e. g.), unstable liver disease, uncontrolled cardiovascular disease, ongoing active infectious disease.
* Subjects with QT interval corrected (QTc) greater than 450 millisecond (msec) or QTc greater than 480 msec in subjects with bundle branch block based on local Electrocardiogram (EGC) reading.
* Subjects who discontinue study treatment based on liver chemistry stopping criteria during Study 200622.
* 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).
* 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 the first dose, other than Study 200622 study treatment. The term "investigational" applies to any drug not approved for sale for the disease/indication to treat in the country in which it is being used or investigational formulations of marketed products.
* Subjects who are currently participating in any other interventional clinical study.
* Subjects had an AE (serious or non-serious) considered related to study treatment while participating in Study 200622 which resulted in permanent withdrawal of study treatment.

Primary outcomes:
measure: Number of Participants With Common (>=3%) Non-serious Adverse Events (AEs)
timeFrame: Up to Week 20
measure: Number of Participants With Serious AEs
timeFrame: Up to Week 28
measure: Number of Participants With the Presence of Anti-drug Antibody
timeFrame: Baseline (Day 1), Week 20 and Week 28
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: GSK Investigational Site
state: California
city: New Haven
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Mayfield Heights
country: United States
facility: GSK Investigational Site
state: Ohio
city: Murray
country: United States
facility: GSK Investigational Site
state: Utah
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
state: Rio Grande Do Sul
city: Santo André - SP
country: Brazil
facility: GSK Investigational Site
state: São Paulo
city: Sorocaba
country: Brazil
facility: GSK Investigational Site
state: São Paulo
city: Lille Cedex
country: France
facility: GSK Investigational Site
city: Nantes Cedex 1
country: France
facility: GSK Investigational Site
city: Suresnes
country: France
facility: GSK Investigational Site
city: Toulouse Cedex 9
country: France
facility: GSK Investigational Site
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Fulda
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Kirchheim unter Teck
country: Germany
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: Firenze
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Villahermosa
country: Mexico
facility: GSK Investigational Site
state: Tabasco
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Targu Mures
country: Romania
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Leicester
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gleich 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.