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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03306043
• Collaborator: (none)
• Enrollment: 102
• Locations: 36
• Arm: 1
• Actual Duration (Months): 25.5
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

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participate in this extension study if they had completed the 32-Week treatment period in study 200622 or if they were withdrawn from the study pre-maturely, but were continued in the study per protocol until 32 Weeks from randomization.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

Condition or Disease	Intervention/Treatment	Phase
Hypereosinophilic Syndrome	Drug: Mepolizumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: A single group of subjects will receive 300 mg SC mepolizumab every 4 Weeks.A single group of subjects will receive 300 mg SC mepolizumab every 4 Weeks.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 13, 2017
• Actual Primary Completion Date: Dec 30, 2019
• Actual Study Completion Date: Dec 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subjects who received mepolizumab 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; 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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	La Jolla	California	United States	92093
2	GSK Investigational Site	New Haven	Connecticut	United States	06520
3	GSK Investigational Site	Rochester	Minnesota	United States	55905
4	GSK Investigational Site	Cincinnati	Ohio	United States	45229
5	GSK Investigational Site	Mayfield Heights	Ohio	United States	44124
6	GSK Investigational Site	Murray	Utah	United States	84107
7	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1028AAP
8	GSK Investigational Site	La Plata	Buenos Aires	Argentina
9	GSK Investigational Site	Mar del Plata	Buenos Aires	Argentina	7600
10	GSK Investigational Site	Bruxelles		Belgium	1070
11	GSK Investigational Site	Leuven		Belgium	3000
12	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul	Brazil	40110-160
13	GSK Investigational Site	Santo André - SP	São Paulo	Brazil	09080-110
14	GSK Investigational Site	Sorocaba	São Paulo	Brazil	18040-425
15	GSK Investigational Site	Lille Cedex		France	59037
16	GSK Investigational Site	Nantes Cedex 1		France	44093
17	GSK Investigational Site	Suresnes		France	92151
18	GSK Investigational Site	Toulouse Cedex 9		France	31059
19	GSK Investigational Site	Mannheim	Baden-Wuerttemberg	Germany	68167
20	GSK Investigational Site	Fulda	Hessen	Germany	36043
21	GSK Investigational Site	Hannover	Niedersachsen	Germany	30625
22	GSK Investigational Site	Kirchheim unter Teck		Germany	73230
23	GSK Investigational Site	Napoli	Campania	Italy	80131
24	GSK Investigational Site	Firenze	Toscana	Italy	50134
25	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44100
26	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64060
27	GSK Investigational Site	Villahermosa	Tabasco	Mexico	86035
28	GSK Investigational Site	Krakow		Poland	31-066
29	GSK Investigational Site	Lodz		Poland	90-153
30	GSK Investigational Site	Bucharest		Romania	010306
31	GSK Investigational Site	Targu Mures		Romania	540327
32	GSK Investigational Site	Moscow		Russian Federation	125167
33	GSK Investigational Site	Saint-Petersburg		Russian Federation	197341
34	GSK Investigational Site	Barcelona		Spain	08036
35	GSK Investigational Site	Valencia		Spain	46026
36	GSK Investigational Site	Leicester		United Kingdom	LE3 9QP

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Nov 16, 2017
• Statistical Analysis Plan - Jun 18, 2019

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03306043
• Other Study ID Numbers: 205203; 2017-000184-32
• First Posted: Oct 10, 2017
• Last Update Posted: Jun 23, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: hypereosinophilic syndrome; hypereosinophilic syndrome flare; open-label extension study; Mepolizumab; SB240563; Long-term safety
• Additional relevant MeSH terms: Hypereosinophilic Syndrome; Syndrome

Study Results

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 Detail	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.

Arm/Group Title	Mepolizumab 300 mg SC
Arm/Group Description	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).
Period Title: Overall Study
STARTED	102
COMPLETED	98
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Mepolizumab 300 mg SC
Arm/Group Description	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).
Overall Participants	102
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46.0 (15.54)
Sex: Female, Male (Count of Participants)
Female	55 53.9%
Male	47 46.1%
Race/Ethnicity, Customized (Count of Participants)
Asian-East Asian Heritage	1 1%
Black or African American	2 2%
White-White/Caucasian/European Heritage	79 77.5%
American Indian or Alaskan Native	3 2.9%
Unknown	17 16.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety Population comprised of all participants who received at least one dose of open-label mepolizumab.

Arm/Group Title	Mepolizumab 300 mg SC
Arm/Group Description	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).
Measure Participants	102
Count of Participants [Participants]	34 33.3%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Mepolizumab 300 mg SC
Arm/Group Description	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).
Measure Participants	102
Count of Participants [Participants]	9 8.8%

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Mepolizumab 300 mg SC
Arm/Group Description	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).
Measure Participants	102
Baseline, Negative, n=102	101 99%
Baseline, Positive, n=102	1 1%
Week 20, Negative, n=101	101 99%
Week 20, Positive, n=101	0 0%
Week 28, Negative, n=14	14 13.7%
Week 28, Positive, n=14	0 0%

Adverse Events

Time Frame	Serious AEs were reported from start of study (Week 0) up to end of study (up to Week 28) and non-serious AEs were reported from start of study treatment until 28 days after last dose (up to Week 20)
Adverse Event Reporting Description	Non-serious AEs and serious AEs were reported for Safety Population.
Arm/Group Title	Mepolizumab 300 mg SC
Arm/Group Description	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).
All Cause Mortality
	Mepolizumab 300 mg SC
	Affected / at Risk (%)	# Events
Total	0/102 (0%)
Serious Adverse Events
	Mepolizumab 300 mg SC
	Affected / at Risk (%)	# Events
Total	9/102 (8.8%)
Blood and lymphatic system disorders
Hypereosinophilic syndrome	1/102 (1%)	1
Gastrointestinal disorders
Gastroenteritis eosinophilic	1/102 (1%)	1
Infections and infestations
Bacteraemia	1/102 (1%)	1
Clostridium difficile colitis	1/102 (1%)	1
Diverticulitis	1/102 (1%)	1
Gastrointestinal infection	1/102 (1%)	1
Infective exacerbation of bronchiectasis	1/102 (1%)	1
Mycobacterium abscessus infection	1/102 (1%)	1
Perihepatic abscess	1/102 (1%)	1
Pneumonia	1/102 (1%)	1
Sinusitis	1/102 (1%)	1
Injury, poisoning and procedural complications
Joint dislocation	1/102 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Peripheral T-cell lymphoma unspecified	1/102 (1%)	1
Other (Not Including Serious) Adverse Events
	Mepolizumab 300 mg SC
	Affected / at Risk (%)	# Events
Total	34/102 (33.3%)
Gastrointestinal disorders
Diarrhoea	12/102 (11.8%)	13
Vomiting	6/102 (5.9%)	7
Constipation	5/102 (4.9%)	6
Nausea	5/102 (4.9%)	5
General disorders
Fatigue	4/102 (3.9%)	4
Injection site reaction	4/102 (3.9%)	11
Infections and infestations
Nasopharyngitis	5/102 (4.9%)	5
Bronchitis	4/102 (3.9%)	4
Sinusitis	4/102 (3.9%)	4
Upper respiratory tract infection	4/102 (3.9%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	5/102 (4.9%)	6
Nervous system disorders
Headache	6/102 (5.9%)	7
Skin and subcutaneous tissue disorders
Pruritus	7/102 (6.9%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.