Hypereosinophilic Syndrome
Conditions
Keywords
hypereosinophilic syndrome, hypereosinophilic syndrome flare, open-label extension study, Mepolizumab, SB240563, Long-term safety
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participate in this extension study if they had completed the 32-Week treatment period in study 200622 or if they were withdrawn from the study pre-maturely, but were continued in the study per protocol until 32 Weeks from randomization.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.
Interventions
DRUGMepolizumab
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.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A single group of subjects will receive 300 mg SC mepolizumab every 4 Weeks.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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205203, subjects from study 200622 must have completed 32-Week treatment period in the study or if the subject was withdrawn from study treatment prematurely during the 200622 study, but continued in the study per protocol (including HES flare-related assessments) until 32 Weeks from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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Common (>=3%) Non-serious Adverse Events (AEs) | Up to Week 20 | 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 | Up to Week 28 | 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 | Baseline (Day 1), Week 20 and Week 28 | 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. |
Countries
Argentina, Belgium, Brazil, France, Germany, Italy, Mexico, Poland, Romania, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
This was a multi-center, open-label extension study to evaluate the long-term safety profile of mepolizumab in participants with Hypereosinophilic Syndrome (HES). In this study, participants received open-label mepolizumab 300 milligram (mg) subcutaneously (SC).
Pre-assignment details
A total of 102 participants who completed the parent study (200622 \[NCT02836496\]) and met the eligibility criteria were enrolled in this open-label extension study.
Participants by arm
| Arm | Count |
|---|---|
| Mepolizumab 300 mg SC Participants were administered 300 mg SC mepolizumab every 4 weeks (starting approximately 32 weeks after the first dose of study treatment in Study 200622). The final dose of mepolizumab was administered at Visit 5 (Week 16). | 102 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Mepolizumab 300 mg SC |
|---|---|
| Age, Continuous | 46.0 Years STANDARD_DEVIATION 15.54 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 3 Participants |
| Race/Ethnicity, Customized Asian-East Asian Heritage | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Unknown | 17 Participants |
| Race/Ethnicity, Customized White-White/Caucasian/European Heritage | 79 Participants |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 102 |
| other Total, other adverse events | 34 / 102 |
| serious Total, serious adverse events | 9 / 102 |
Outcome results
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.
Time frame: Up to Week 20
Population: Safety Population comprised of all participants who received at least one dose of open-label mepolizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mepolizumab 300 mg SC | Number of Participants With Common (>=3%) Non-serious Adverse Events (AEs) | 34 Participants |
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.
Time frame: Up to Week 28
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mepolizumab 300 mg SC | Number of Participants With Serious AEs | 9 Participants |
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.
Time frame: Baseline (Day 1), Week 20 and Week 28
Population: Safety Population. Only those participants with data available at specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mepolizumab 300 mg SC | Number of Participants With the Presence of Anti-drug Antibody | Baseline, Negative, n=102 | 101 Participants |
| Mepolizumab 300 mg SC | Number of Participants With the Presence of Anti-drug Antibody | Baseline, Positive, n=102 | 1 Participants |
| Mepolizumab 300 mg SC | Number of Participants With the Presence of Anti-drug Antibody | Week 20, Negative, n=101 | 101 Participants |
| Mepolizumab 300 mg SC | Number of Participants With the Presence of Anti-drug Antibody | Week 20, Positive, n=101 | 0 Participants |
| Mepolizumab 300 mg SC | Number of Participants With the Presence of Anti-drug Antibody | Week 28, Negative, n=14 | 14 Participants |
| Mepolizumab 300 mg SC | Number of Participants With the Presence of Anti-drug Antibody | Week 28, Positive, n=14 | 0 Participants |