Trial Outcomes & Findings for A Multi-center, Open-label Extension, Safety Study of Mepolizumab in Subjects With Hypereosinophilic Syndrome (HES) From Study 200622 (NCT NCT03306043)

Last Updated: 2020-06-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

102 participants

Primary outcome timeframe

Up to Week 20

Results posted on

2020-06-23

Participant Flow

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).

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.

Participant milestones

Participant milestones
Measure	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).
Overall Study STARTED	102
Overall Study COMPLETED	98
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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).
Overall Study Adverse Event	1
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mepolizumab 300 mg SC n=102 Participants 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).
Age, Continuous	46.0 Years STANDARD_DEVIATION 15.54 • n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants
Race/Ethnicity, Customized White-White/Caucasian/European Heritage	79 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	3 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 20

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

Outcome measures

Outcome measures
Measure	Mepolizumab 300 mg SC n=102 Participants 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).
Number of Participants With Common (>=3%) Non-serious Adverse Events (AEs)	34 Participants

PRIMARY outcome

Timeframe: Up to Week 28

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Mepolizumab 300 mg SC n=102 Participants 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).
Number of Participants With Serious AEs	9 Participants

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Mepolizumab 300 mg SC n=102 Participants 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).
Number of Participants With the Presence of Anti-drug Antibody Baseline, Negative, n=102	101 Participants
Number of Participants With the Presence of Anti-drug Antibody Baseline, Positive, n=102	1 Participants
Number of Participants With the Presence of Anti-drug Antibody Week 20, Positive, n=101	0 Participants
Number of Participants With the Presence of Anti-drug Antibody Week 20, Negative, n=101	101 Participants
Number of Participants With the Presence of Anti-drug Antibody Week 28, Negative, n=14	14 Participants
Number of Participants With the Presence of Anti-drug Antibody Week 28, Positive, n=14	0 Participants

Adverse Events

Mepolizumab 300 mg SC

Serious events: 9 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Mepolizumab 300 mg SC n=102 participants at risk 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).
Infections and infestations Bacteraemia	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Clostridium difficile colitis	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Diverticulitis	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Gastrointestinal infection	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Infective exacerbation of bronchiectasis	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Mycobacterium abscessus infection	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Perihepatic abscess	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Pneumonia	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Sinusitis	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Blood and lymphatic system disorders Hypereosinophilic syndrome	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Gastrointestinal disorders Gastroenteritis eosinophilic	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Injury, poisoning and procedural complications Joint dislocation	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peripheral T-cell lymphoma unspecified	0.98% 1/102 • Number of events 1 • 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) Non-serious AEs and serious AEs were reported for Safety Population.

Other adverse events

Other adverse events
Measure	Mepolizumab 300 mg SC n=102 participants at risk 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).
Gastrointestinal disorders Diarrhoea	11.8% 12/102 • Number of events 13 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Gastrointestinal disorders Vomiting	5.9% 6/102 • Number of events 7 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Gastrointestinal disorders Constipation	4.9% 5/102 • Number of events 6 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Gastrointestinal disorders Nausea	4.9% 5/102 • Number of events 5 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Nasopharyngitis	4.9% 5/102 • Number of events 5 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Bronchitis	3.9% 4/102 • Number of events 4 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Sinusitis	3.9% 4/102 • Number of events 4 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Infections and infestations Upper respiratory tract infection	3.9% 4/102 • Number of events 4 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
General disorders Fatigue	3.9% 4/102 • Number of events 4 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
General disorders Injection site reaction	3.9% 4/102 • Number of events 11 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Skin and subcutaneous tissue disorders Pruritus	6.9% 7/102 • Number of events 7 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Nervous system disorders Headache	5.9% 6/102 • Number of events 7 • 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) Non-serious AEs and serious AEs were reported for Safety Population.
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 5/102 • Number of events 6 • 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) Non-serious AEs and serious AEs were reported for Safety Population.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER