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A Multi-center, Open-label Extension, Safety Study of Mepolizumab in Subjects With Hypereosinophilic Syndrome (HES) From Study 200622

Primary Purpose

Hypereosinophilic Syndrome

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Mepolizumab
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypereosinophilic Syndrome focused on measuring hypereosinophilic syndrome, hypereosinophilic syndrome flare, open-label extension study, Mepolizumab, SB240563, Long-term safety

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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205203, subjects from study 200622 must have completed 32-Week treatment period in the study or if the subject was withdrawn from study treatment prematurely during the 200622 study, but continued in the study per protocol (including HES flare-related assessments) until 32 Weeks from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.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Subjects who received mepolizumab

Arm Description

Subjects who were part of study 200622 and were randomized to receive either placebo or mepolizumab will be enrolled in this study as per study eligibility criteria. In this study, subjects will receive 300 mg of mepolizumab SC (three 100 mg SC injections) every 4 Weeks for a total of 5 doses during 20-Week treatment period.

Outcomes

Primary Outcome Measures

Number of Participants With Common (>=3%) Non-serious Adverse Events (AEs)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-serious AEs from start of study treatment until 28 days after last dose (up to Week 20) are reported. Number of participants with common (>=3% incidence) non-serious AEs are presented.
Number of Participants With Serious AEs
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with serious AEs are presented.
Number of Participants With the Presence of Anti-drug Antibody
Blood samples were analyzed for the presence of anti-mepolizumab antibodies by binding anti-drug antibody (ADA) assay. The binding ADA assay results at each visit were summarized as negative or positive. The binding ADA assay was performed in three steps; screening, confirmation and titration. The screening assay produced a result of positive or negative relative to a screening cut point. Positive samples continued with the confirmation assay, which also produced a result of positive or negative relative to a confirmation cut point. For positive confirmation samples, a titre value was obtained to quantify the degree of binding in a titration assay. Participants were considered 'Positive' if they had a positive confirmation ADA assay result.

Secondary Outcome Measures

Full Information

First Posted
October 5, 2017
Last Updated
June 4, 2020
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT03306043
Brief Title
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

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
November 13, 2017 (Actual)
Primary Completion Date
December 30, 2019 (Actual)
Study Completion Date
December 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypereosinophilic Syndrome
Keywords
hypereosinophilic syndrome, hypereosinophilic syndrome flare, open-label extension study, Mepolizumab, SB240563, Long-term safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
A single group of subjects will receive 300 mg SC mepolizumab every 4 Weeks.
Masking
None (Open Label)
Allocation
N/A
Enrollment
102 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Subjects who received mepolizumab
Arm Type
Experimental
Arm Description
Subjects who were part of study 200622 and were randomized to receive either placebo or mepolizumab will be enrolled in this study as per study eligibility criteria. In this study, subjects will receive 300 mg of mepolizumab SC (three 100 mg SC injections) every 4 Weeks for a total of 5 doses during 20-Week treatment period.
Intervention Type
Drug
Intervention Name(s)
Mepolizumab
Intervention Description
Mepolizumab will be available as 100 mg vial for injection. Subjects will receive three 100 mg SC injections for every 4 Weeks for a total of 5 doses during 20 Week treatment period.
Primary Outcome Measure Information:
Title
Number of Participants With Common (>=3%) Non-serious Adverse Events (AEs)
Description
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-serious AEs from start of study treatment until 28 days after last dose (up to Week 20) are reported. Number of participants with common (>=3% incidence) non-serious AEs are presented.
Time Frame
Up to Week 20
Title
Number of Participants With Serious AEs
Description
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious AE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with serious AEs are presented.
Time Frame
Up to Week 28
Title
Number of Participants With the Presence of Anti-drug Antibody
Description
Blood samples were analyzed for the presence of anti-mepolizumab antibodies by binding anti-drug antibody (ADA) assay. The binding ADA assay results at each visit were summarized as negative or positive. The binding ADA assay was performed in three steps; screening, confirmation and titration. The screening assay produced a result of positive or negative relative to a screening cut point. Positive samples continued with the confirmation assay, which also produced a result of positive or negative relative to a confirmation cut point. For positive confirmation samples, a titre value was obtained to quantify the degree of binding in a titration assay. Participants were considered 'Positive' if they had a positive confirmation ADA assay result.
Time Frame
Baseline (Day 1), Week 20 and Week 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
GSK Investigational Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
GSK Investigational Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
GSK Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
GSK Investigational Site
City
Mayfield Heights
State/Province
Ohio
ZIP/Postal Code
44124
Country
United States
Facility Name
GSK Investigational Site
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
GSK Investigational Site
City
Ciudad Autonoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1028AAP
Country
Argentina
Facility Name
GSK Investigational Site
City
La Plata
State/Province
Buenos Aires
Country
Argentina
Facility Name
GSK Investigational Site
City
Mar del Plata
State/Province
Buenos Aires
ZIP/Postal Code
7600
Country
Argentina
Facility Name
GSK Investigational Site
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
GSK Investigational Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
GSK Investigational Site
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
40110-160
Country
Brazil
Facility Name
GSK Investigational Site
City
Santo André - SP
State/Province
São Paulo
ZIP/Postal Code
09080-110
Country
Brazil
Facility Name
GSK Investigational Site
City
Sorocaba
State/Province
São Paulo
ZIP/Postal Code
18040-425
Country
Brazil
Facility Name
GSK Investigational Site
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
GSK Investigational Site
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
GSK Investigational Site
City
Suresnes
ZIP/Postal Code
92151
Country
France
Facility Name
GSK Investigational Site
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
GSK Investigational Site
City
Mannheim
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
68167
Country
Germany
Facility Name
GSK Investigational Site
City
Fulda
State/Province
Hessen
ZIP/Postal Code
36043
Country
Germany
Facility Name
GSK Investigational Site
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
GSK Investigational Site
City
Kirchheim unter Teck
ZIP/Postal Code
73230
Country
Germany
Facility Name
GSK Investigational Site
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
GSK Investigational Site
City
Firenze
State/Province
Toscana
ZIP/Postal Code
50134
Country
Italy
Facility Name
GSK Investigational Site
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44100
Country
Mexico
Facility Name
GSK Investigational Site
City
Monterrey
State/Province
Nuevo León
ZIP/Postal Code
64060
Country
Mexico
Facility Name
GSK Investigational Site
City
Villahermosa
State/Province
Tabasco
ZIP/Postal Code
86035
Country
Mexico
Facility Name
GSK Investigational Site
City
Krakow
ZIP/Postal Code
31-066
Country
Poland
Facility Name
GSK Investigational Site
City
Lodz
ZIP/Postal Code
90-153
Country
Poland
Facility Name
GSK Investigational Site
City
Bucharest
ZIP/Postal Code
010306
Country
Romania
Facility Name
GSK Investigational Site
City
Targu Mures
ZIP/Postal Code
540327
Country
Romania
Facility Name
GSK Investigational Site
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Saint-Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
GSK Investigational Site
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
GSK Investigational Site
City
Leicester
ZIP/Postal Code
LE3 9QP
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
http://clinicalstudydatarequest.com
Citations:
PubMed Identifier
34389506
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.
Results Reference
derived

Learn more about this trial

A Multi-center, Open-label Extension, Safety Study of Mepolizumab in Subjects With Hypereosinophilic Syndrome (HES) From Study 200622

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