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

NCT03306043 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 2052032017-000184-32
• Study Type: interventional
• Target: 102
• Locations: 13 countries
• Sites: 36

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participate in this extension study if they had completed the 32-Week treatment period in study 200622 or if they were withdrawn from the study pre-maturely, but were continued in the study per protocol until 32 Weeks from randomization.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

Conditions

Hypereosinophilic Syndrome

Keywords

hypereosinophilic syndrome; hypereosinophilic syndrome flare; open-label extension study; Mepolizumab; SB240563; Long-term safety

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Study Arms (1)

Subjects who received mepolizumab

EXPERIMENTAL

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.

Drug: Mepolizumab

Interventions

Mepolizumab DRUG

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.

Subjects who received mepolizumab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (36)

GSK Investigational Site

La Jolla, California, 92093, United States

Location

GSK Investigational Site

New Haven, Connecticut, 06520, United States

Location

GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45229, United States

Location

GSK Investigational Site

Mayfield Heights, Ohio, 44124, United States

Location

GSK Investigational Site

Murray, Utah, 84107, United States

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1028AAP, Argentina

Location

GSK Investigational Site

La Plata, Buenos Aires, Argentina

Location

GSK Investigational Site

Mar del Plata, Buenos Aires, 7600, Argentina

Location

GSK Investigational Site

Brussels, 1070, Belgium

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Porto Alegre, Rio Grande do Sul, 40110-160, Brazil

Location

GSK Investigational Site

Santo André - SP, São Paulo, 09080-110, Brazil

Location

GSK Investigational Site

Sorocaba, São Paulo, 18040-425, Brazil

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Suresnes, 92151, France

Location

GSK Investigational Site

Toulouse, 31059, France

Location

GSK Investigational Site

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

GSK Investigational Site

Fulda, Hesse, 36043, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Kirchheim unter Teck, 73230, Germany

Location

GSK Investigational Site

Napoli, Campania, 80131, Italy

Location

GSK Investigational Site

Florence, Tuscany, 50134, Italy

Location

GSK Investigational Site

Guadalajara, Jalisco, 44100, Mexico

Location

GSK Investigational Site

Monterrey, Nuevo León, 64060, Mexico

Location

GSK Investigational Site

Villahermosa, Tabasco, 86035, Mexico

Location

GSK Investigational Site

Krakow, 31-066, Poland

Location

GSK Investigational Site

Lodz, 90-153, Poland

Location

GSK Investigational Site

Bucharest, 010306, Romania

Location

GSK Investigational Site

Târgu Mureş, 540327, Romania

Location

GSK Investigational Site

Moscow, 125167, Russia

Location

GSK Investigational Site

Saint Petersburg, 197341, Russia

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

Location

GSK Investigational Site

Leicester, LE3 9QP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34389506 DERIVED

MeSH Terms

Conditions

Hypereosinophilic Syndrome

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: A single group of subjects will receive 300 mg SC mepolizumab every 4 Weeks.

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: October 10, 2017
• Study Start: November 13, 2017
• Primary Completion: December 30, 2019
• Study Completion: December 30, 2019
• Last Updated: June 23, 2020
• Results First Posted: June 23, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• 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.

Locations

RO (2); GB (1); US (6); PL (2); FR (4); AR (3); DE (4); IT (2); ME (3); RU (2); ES (2); BR (3); BE (2)