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

Hypereosinophilic Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03306043
• Other study ID #: 205203
• Secondary ID: 2017-000184-32
• Status: Completed
• Phase: Phase 3
• Start date: November 13, 2017
• Est. completion date: December 30, 2019

Study information

• Verified date: June 2020
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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participate in this extension study if they had completed the 32-Week treatment period in study 200622 or if they were withdrawn from the study pre-maturely, but were continued in the study per protocol until 32 Weeks from randomization.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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: December 30, 2019
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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205203, subjects from study 200622 must have completed 32-Week treatment period in the study or if the subject was withdrawn from study treatment prematurely during the 200622 study, but continued in the study per protocol (including HES flare-related assessments) until 32 Weeks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

Related Conditions & MeSH terms

• Hypereosinophilic Syndrome
• Syndrome

Intervention

Drug:
• Mepolizumab
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.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Leuven
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Santo André - SP	São Paulo
Brazil	GSK Investigational Site	Sorocaba	São Paulo
France	GSK Investigational Site	Lille Cedex
France	GSK Investigational Site	Nantes Cedex 1
France	GSK Investigational Site	Suresnes
France	GSK Investigational Site	Toulouse Cedex 9
Germany	GSK Investigational Site	Fulda	Hessen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Kirchheim unter Teck
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Italy	GSK Investigational Site	Firenze	Toscana
Italy	GSK Investigational Site	Napoli	Campania
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Villahermosa	Tabasco
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lodz
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Targu Mures
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Saint-Petersburg
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Valencia
United Kingdom	GSK Investigational Site	Leicester
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	La Jolla	California
United States	GSK Investigational Site	Mayfield Heights	Ohio
United States	GSK Investigational Site	Murray	Utah
United States	GSK Investigational Site	New Haven	Connecticut
United States	GSK Investigational Site	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  France,  Germany,  Italy,  Mexico,  Poland,  Romania,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to Week 20
Primary	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.	Up to Week 28
Primary	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.	Baseline (Day 1), Week 20 and Week 28