Open-Label Extension Of Intravenous Mepolizumab In Patients With Hypereosinophilic Syndrome

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00097370
• Collaborator: (none)
• Enrollment: 78
• Locations: 24
• Arm: 1
• Actual Duration (Months): 72
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is an open label study of mepolizumab 750 mg intravenous in those subjects who participated in study 100185 to evaluate the long term safety and efficacy of mepolizumab in subjects with hypereosinophilic syndrome. The study will also evaluate the optimal dosing frequency for clinical use, the effects on corticosteroid reduction, and decrease of signs and symptoms of Hypereosinophilic Syndrome.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Extension Study to Evaluate Safety and Efficacy of Mepolizumab in Patients With Hypereosinophilic Syndromes
• Actual Study Start Date: Sep 30, 2004
• Actual Primary Completion Date: Sep 29, 2010
• Actual Study Completion Date: Sep 29, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mepolizumab 750mg Intravenous, monthly and individual dosing schedule	Drug: mepolizumab; Study Drug

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Adverse Event (AE) During the Treatment Phase [From the first dose of study medication up to 7 days after the last dose (up to approximately 6 years)]

   An AE is any untoward medical occurrence in clinical investigation participants temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs are summarized by Treatment phase. Safety and tolerability of the study drug was assessed by number of participants with any AE

2. Number of Participants With Any Adverse Event (AE) During the Follow-up Phase [From end of Treatment Phase up to 97 days after the last dose date (up to approximately 6 years)]

   An AE is any untoward medical occurrence in clinical investigation participants temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs are summarized by Follow-up phase. Safety and tolerability of the study drug was assessed by number of participants with any AE

Secondary Outcome Measures

1. Number of Participants Achieving a Prednisone Level of =<10 mg (as Sole Background Therapy) at the End of Study [up to approximately 6 years]

   Participants who were receiving a prednisone dose level of =<10 mg as their sole background therapy at the end of the study were included for the analysis.

2. Number of Participants Achieving an Eosinophil Level of < 600 Cell/Microliter (uL) (in Addition to the Lowest Background Therapy) at the End of Study [up to approximately 6 years]

   The criteria for eosinophil count was achieved if the participant's eosinophil count remained below <600 cell/uL for the last observation on study i.e. within length of dosing cycle + 7 days of last dose of study drug. For participants who entered in Stage 1, HES medications taking prior to the first infusion date in Stage 2 were considered as the lowest background therapy. For participants who entered in Stage 2, HES medications taken on the date that immediately preceded the first infusion date of study drug and had not been discontinued was regarded as the lowest background therapy. If the dose of the lowest background therapy had increased or the medication had changed or the participant had not reached their lowest background therapy, the participant was regarded as not achieving this endpoint.

3. For Those Participants Who Completed 9 Months of Dosing in Study MHE100185 and Achieved a Prednisone Level <=10 mg: Number of Participants Achieving <= 10 mg Prednisone (as Sole Background Therapy) for >= 3months [up to approximately 6 years]

   Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of <=10 mg of prednisone at study end were analyzed. Duration of doses <=10 mg was determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If it did, then the number of days <=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months).

4. For Those Participants Who Completed 9 Months of Dosing in Study MHE100185 and Achieved a Prednisone Level >10 mg: Number of Participants Achieving <=10 mg Prednisone (as Sole Background Therapy) for >= 8 Weeks [up to approximately 6 years]

   Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of prednisone of >10 mg at the end of the study were analyzed. Duration of doses <= 10 mg were determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If overap occurred, then the number of days <=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 53 days (8 weeks).

5. For Those Participants Who Entered Stage 2 From Study MHE100185 With a Prednisone Level of <=10 mg Prednisone: Number of Participants Achieving a Prednisone Dose <=10 mg (as Sole Background Therapy) for >=3 Months; [up to approximately 6 years]

   Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of <=10 mg of prednisone at study end and participants who withdrew from the study early who were at a prednisone dose level <=10 mg were analyzed. Duration of doses <= 10 mg were determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If overlap occurred, then the number of days <=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months).

6. For Those Participants Who Entered Stage 1 From Study MHE100185 With >10 mg Prednisone: Number of Participants Achieving a Prednisone Dose <=10 mg (as Sole Background Therapy) for>=3 Months [up to approximately 6 years]

   Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of >10 mg prednisone at the end of the study and participants who withdrew from the study early who were at a prednisone dose level >10 mg were analyzed. Duration of doses <= 10 mg was determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they do not overlap with the steroid dosing dates. If it did, then the number of days <=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months)

7. Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3 [up to approximately 6 years]

   Mean blood eosinophil counts were summarized over time taking into account the effect of HES background therapy. Eosinophil count observations for only those participants taking mepolizumab in conjunction with prednisone or as monotherapy were included.

8. Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2 [up to approximately 6 years]

   The number of participants at the end of Stage 2 with study medication dosing frequencies of 4 weeks, 5-6 weeks, 7-8 weeks, 9-10 weeks, 11-12 weeks, 13-16 weeks, 17-20 weeks, 21-24 weeks and >24 weeks were summarized. The first infusion date in Stage 3 and the last infusion date in Stage 2 were used to calculate the dosing frequency.

9. Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter [Baseline and up to approximately 6 years]

   The pruritus visual analogue scale asks participants to rate the status of their Pruritus based on the severity of their itch. Scores range from 0-100 with 0 = No itch and 100 = Worst imaginable itch. Change from Baseline in pVAS score is the difference between the pVAS score at the time point being considered to the MHE100901 Baseline score.

10. Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter [Baseline and up to approximately 6 years]

    The erythema subscale score and edema subscale score are each graded on a 0-3 scale, with 0 = absent , 1 = mild, 2 = moderate, 3 = severe. The total score ranged from 0 to 6, with higher scores indicative of more severe Erythema/Edema. The total score was obtained by summing together the responses for each of the two subscale items. Change from Baseline in erythema/edema total score is the difference between erythema/edema total score at the time point being analyzed to the MHE100901 Baseline score..

11. Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter [Baseline and up to approximately 6 years]

    The SF-12v2 is the 12 item abbreviated form of SF-36v2 survey . It provides information about how participants feel, and how well they have been able to perform their usual activities, over the past 4 weeks. SF-12v2 questions make up 8 scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health . Transformed physical component summary score (PCS-12) is derived using all the 12 items and scored onto a 0-100 scale such that a higher score indicates a better health state and better functioning. Change from Baseline in scale or summary measure score is the difference between the score at the time point being analyzed to Baseline.

12. Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter [Baseline and up to approximately 6 years]

    The SF-12v2 is the 12 item abbreviated form of SF-36v2 survey developed by the Medical Outcomes Trust and QualityMetric Incorporated. It provides information about how participants feel, and how well they have been able to perform their usual activities, over the past 4 weeks. SF-12v2 scale questions make up 8 scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health are for mental component summary. Transformed mental component summary score (MCS-12) is derived using all the 12 items and scored onto a 0-100 scale such that a higher score indicates a better health state and better functioning. Change from Baseline in scale or summary measure score is the difference between the score at the time point being analyzed to Baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Signed informed consent.

• Subjects who have participated in Study MHE100185 and have been administered at least 2 doses of study medication.

• Not pregnant or nursing

• Of non-childbearing potential (i.e., women who had a hysterectomy, are post-menopausal which is defined as 1 year without menses, have both ovaries surgically removed, or have current documented tubule ligation); or

• Of childbearing potential (i.e., women with functional ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category includes women with oligomenorrhoea [even severe], women who are perimenopausal or have just begun to menstruate. These women must have a negative serum pregnancy test at the Screening Visit, and agree to one of the following:1). Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of investigational product until 3 months after the last dose of investigational product; Or 2). Consistent and correct use of one of the following acceptable methods of birth control for one month prior to the start of the investigation product and three months after the last dose:Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for the female subjects; Implants of levonorgestrel;Injectable progestogen;Any intrauterine device (IUD) with a documented failure rate of less than 1% per year; Oral contraceptives (either combined or progestogen only)

Exclusion criteria:

• Has developed life-threatening or other serious illness or clinical manifestation deemed inappropriate for inclusion in study per the principal investigator

• Has any of the following abnormal laboratory values at the Week36/EW Visit of Study MHE100185: • Serum creatinine ≥3 times institutional upper limit normal (ULN); • AST or/ALT ≥5 times institutional ULN; • Platelet count < 50,000/uL

• Has developed abnormal cardiac functions, as the following, within past 3 months:• Left ventricular ejection fraction (LVEF) < 20%; • NYHA class IIIb or IV; • Angina or acute myocardial infarction

• Has developed allergic reaction to Study MHE100185 investigational product Use of an investigational drug as concurrent medication

• Does not complete Week36/EW Visit assessments required in Study MHE100185

• Has completed or been terminated from Study MHE100185 for more than 1 month

• Recent history or suspicion of current drug abuse or alcohol abuse within the last 6 months

• Positive pregnancy test at the Week36/EW Visit of Study MHE100185

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	San Diego	California	United States	92103
2	GSK Investigational Site	Denver	Colorado	United States	80206
3	GSK Investigational Site	Bethesda	Maryland	United States	20892
4	GSK Investigational Site	Boston	Massachusetts	United States	02215
5	GSK Investigational Site	Rochester	Minnesota	United States	55905
6	GSK Investigational Site	Cincinnati	Ohio	United States	45229
7	GSK Investigational Site	Nashville	Tennessee	United States	37203-1424
8	GSK Investigational Site	Salt Lake City	Utah	United States	84132
9	GSK Investigational Site	Richmond	Virginia	United States	23298
10	GSK Investigational Site	Madison	Wisconsin	United States	53705
11	GSK Investigational Site	St Leonards	New South Wales	Australia	2065
12	GSK Investigational Site	West Perth	Western Australia	Australia	6005
13	GSK Investigational Site	Bruxelles		Belgium	1070
14	GSK Investigational Site	Leuven		Belgium	3000
15	GSK Investigational Site	Winnipeg	Manitoba	Canada	R3C 0N2
16	GSK Investigational Site	Halifax	Nova Scotia	Canada	B3H 1V7
17	GSK Investigational Site	Hamilton	Ontario	Canada	L8N 3Z5
18	GSK Investigational Site	Toronto	Ontario	Canada	M5V 2T3
19	GSK Investigational Site	Lille		France	59000
20	GSK Investigational Site	Suresnes		France	92150
21	GSK Investigational Site	Muenchen	Bayern	Germany	80802
22	GSK Investigational Site	Hannover	Niedersachsen	Germany	30625
23	GSK Investigational Site	Bad Bramstedt	Schleswig-Holstein	Germany	24576
24	GSK Investigational Site	Bologna	Emilia-Romagna	Italy	40138

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00097370
• Other Study ID Numbers: 100901
• First Posted: Nov 23, 2004
• Last Update Posted: Jul 7, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Mepolizumab; Open-label; Anti-IL-5; Hypereosinophilic Syndrome; Hypereosinophilia
• Additional relevant MeSH terms: Hypereosinophilic Syndrome; Syndrome

Study Results

Participant Flow

Recruitment Details	Participants (par.) who completed 9 months of treatment or withdrew from Study MHE100185 after receiving >=2 infusions of study medication were enrolled in this open label extension study. Par. with daily dose of prednisone >10 milligrams (mg) or <=10 mg at the end of Study MHE100185 were enrolled in Stage 1 or Stage 2 of this study, respectively.
Pre-assignment Detail	This study was open-label extension to previous Study MHE100185 (NCT00086658). A total of seventy-eight participants participated in this study. Of these, 38 participants previously received placebo in Study MHE100185 and 40 participants previously received mepolizumab in Study MHE100185.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by intravenous (IV) infusion monthly in Stage 1 along with concomitant hypereosinophilic syndrome (HES)-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Period Title: Stage 1
STARTED	37
COMPLETED	31
NOT COMPLETED	6
Period Title: Stage 1
STARTED	72
COMPLETED	59
NOT COMPLETED	13
Period Title: Stage 1
STARTED	59
COMPLETED	0
NOT COMPLETED	59

Baseline Characteristics

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Overall Participants	78
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	49.2 (14.89)
Sex: Female, Male (Count of Participants)
Female	36 46.2%
Male	42 53.8%
Race/Ethnicity, Customized (Number) [Number]
Arabic/North African	2 2.6%
Black	6 7.7%
East and South East Asian	2 2.6%
South Asian	1 1.3%
White/Caucasian	67 85.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Adverse Event (AE) During the Treatment Phase
Description	An AE is any untoward medical occurrence in clinical investigation participants temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs are summarized by Treatment phase. Safety and tolerability of the study drug was assessed by number of participants with any AE
Time Frame	From the first dose of study medication up to 7 days after the last dose (up to approximately 6 years)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all enrolled participants who received at least one dose of mepolizumab in this study.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	78
Number [Participants]	76 97.4%

2. Primary Outcome

Title	Number of Participants With Any Adverse Event (AE) During the Follow-up Phase
Description	An AE is any untoward medical occurrence in clinical investigation participants temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs are summarized by Follow-up phase. Safety and tolerability of the study drug was assessed by number of participants with any AE
Time Frame	From end of Treatment Phase up to 97 days after the last dose date (up to approximately 6 years)

Outcome Measure Data

Analysis Population Description

Follow-up Population: subset of the modified ITT Population who had evidence of being in the study > length of dosing cycle + 7 days after the date of their last dose of study medication and up to and including 97 days after their last dose date.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	15
Number [Participants]	3 3.8%

3. Secondary Outcome

Title	Number of Participants Achieving a Prednisone Level of =<10 mg (as Sole Background Therapy) at the End of Study
Description	Participants who were receiving a prednisone dose level of =<10 mg as their sole background therapy at the end of the study were included for the analysis.
Time Frame	up to approximately 6 years

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	78
Number [Participants]	62 79.5%

4. Secondary Outcome

Title	Number of Participants Achieving an Eosinophil Level of < 600 Cell/Microliter (uL) (in Addition to the Lowest Background Therapy) at the End of Study
Description	The criteria for eosinophil count was achieved if the participant's eosinophil count remained below <600 cell/uL for the last observation on study i.e. within length of dosing cycle + 7 days of last dose of study drug. For participants who entered in Stage 1, HES medications taking prior to the first infusion date in Stage 2 were considered as the lowest background therapy. For participants who entered in Stage 2, HES medications taken on the date that immediately preceded the first infusion date of study drug and had not been discontinued was regarded as the lowest background therapy. If the dose of the lowest background therapy had increased or the medication had changed or the participant had not reached their lowest background therapy, the participant was regarded as not achieving this endpoint.
Time Frame	up to approximately 6 years

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	78
Number [Participants]	46 59%

5. Secondary Outcome

Title	For Those Participants Who Completed 9 Months of Dosing in Study MHE100185 and Achieved a Prednisone Level <=10 mg: Number of Participants Achieving <= 10 mg Prednisone (as Sole Background Therapy) for >= 3months
Description	Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of <=10 mg of prednisone at study end were analyzed. Duration of doses <=10 mg was determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If it did, then the number of days <=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months).
Time Frame	up to approximately 6 years

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who completed 9 months of dosing in study MHE100185 and achieved a prednisone level <=10 mg were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	43
Number [Participants]	39 50%

6. Secondary Outcome

Title	For Those Participants Who Completed 9 Months of Dosing in Study MHE100185 and Achieved a Prednisone Level >10 mg: Number of Participants Achieving <=10 mg Prednisone (as Sole Background Therapy) for >= 8 Weeks
Description	Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of prednisone of >10 mg at the end of the study were analyzed. Duration of doses <= 10 mg were determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If overap occurred, then the number of days <=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 53 days (8 weeks).
Time Frame	up to approximately 6 years

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who completed 9 months of dosing in study MHE100185 and achieved a prednisone level >10 mg were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	6
Number [Participants]	5 6.4%

7. Secondary Outcome

Title	For Those Participants Who Entered Stage 2 From Study MHE100185 With a Prednisone Level of <=10 mg Prednisone: Number of Participants Achieving a Prednisone Dose <=10 mg (as Sole Background Therapy) for >=3 Months;
Description	Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of <=10 mg of prednisone at study end and participants who withdrew from the study early who were at a prednisone dose level <=10 mg were analyzed. Duration of doses <= 10 mg were determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they did not overlap with the steroid dosing dates. If overlap occurred, then the number of days <=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months).
Time Frame	up to approximately 6 years

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who entered Stage 2 from study MHE100185 with a prednisone level of <=10 mg prednisone were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	48
Number [Participants]	43 55.1%

8. Secondary Outcome

Title	For Those Participants Who Entered Stage 1 From Study MHE100185 With >10 mg Prednisone: Number of Participants Achieving a Prednisone Dose <=10 mg (as Sole Background Therapy) for>=3 Months
Description	Participants from study MHE100185 who completed the 9 months treatment period and achieved a level of >10 mg prednisone at the end of the study and participants who withdrew from the study early who were at a prednisone dose level >10 mg were analyzed. Duration of doses <= 10 mg was determined by examining changes in the prednisone dosing or allowable alternative corticosteroid medication (prednisone equivalents). Start and stop dates of other HES medications were checked to ensure that they do not overlap with the steroid dosing dates. If it did, then the number of days <=10 mg during this overlap was considered as zero and the cumulative days reset to zero, as the endpoint was assessing prednisone dose as sole background therapy. The dosing criteria for this endpoint was considered as achieved if the duration of dosing was minimum of 84 days (3months)
Time Frame	up to approximately 6 years

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who entered Stage 1 from study MHE100185 with >10 mg prednisone were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	30
Number [Participants]	22 28.2%

9. Secondary Outcome

Title	Blood Eosinophil Count (With Consideration of the HES Background Therapy) During Stages 1-3
Description	Mean blood eosinophil counts were summarized over time taking into account the effect of HES background therapy. Eosinophil count observations for only those participants taking mepolizumab in conjunction with prednisone or as monotherapy were included.
Time Frame	up to approximately 6 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	78
MHE100185 Baseline; n=78	456.2 (713.81)
MHE100901 Baseline, n=65	467.2 (719.66)
Week 12; n= 69	176.4 (228.41)
Week 24; n= 68	272.6 (499.78)
Week 48; n= 59	163.1 (146.64)
Week 72; n=49	237.3 (358.36)
Week 96; n=43	272.8 (485.06)
Week 120; n=40	174.3 (172.58)
Week 144; n=36	291.4 (546.03)
Week 168; n=33	210.6 (283.35)
Week 192; n=27	208.5 (249.01)
Week 216; n=23	274.8 (337.50)
Week 240; n=21	138.1 (138.08)
Week 264; n=9	466.7 (533.99)
Week 288; n=2	350.0 (212.13)

10. Secondary Outcome

Title	Number of Participants by Dosing Frequency Groups (Defined as Two Week Dosing Ranges Greater Than a 4 Week Interval) at the End of Stage 2
Description	The number of participants at the end of Stage 2 with study medication dosing frequencies of 4 weeks, 5-6 weeks, 7-8 weeks, 9-10 weeks, 11-12 weeks, 13-16 weeks, 17-20 weeks, 21-24 weeks and >24 weeks were summarized. The first infusion date in Stage 3 and the last infusion date in Stage 2 were used to calculate the dosing frequency.
Time Frame	up to approximately 6 years

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at end of Stage 2 were included.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	59
<4 Weeks	1 1.3%
4 Weeks	5 6.4%
5 to 6 Weeks	6 7.7%
7 to 8 Weeks	4 5.1%
9 to 10 Weeks	5 6.4%
11 to 12 Weeks	8 10.3%
13 to 16 Weeks	12 15.4%
17 to 20 Weeks	8 10.3%
21 to 24 Weeks	4 5.1%
>24 Weeks	6 7.7%

11. Secondary Outcome

Title	Change From Baseline in the Pruritus Visual Analogue Scale (pVAS) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter
Description	The pruritus visual analogue scale asks participants to rate the status of their Pruritus based on the severity of their itch. Scores range from 0-100 with 0 = No itch and 100 = Worst imaginable itch. Change from Baseline in pVAS score is the difference between the pVAS score at the time point being considered to the MHE100901 Baseline score.
Time Frame	Baseline and up to approximately 6 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	73
Week 12; n= 58	-6.8 (20.01)
Week 24; n= 51	-4.5 (17.49)
Week 48; n= 46	-5.1 (26.19)
Week 72; n=39	-0.1 (20.77)
Week 96; n=41	1.0 (27.63)
Week 120; n=38	-0.3 (17.84)
Week 144; n=32	-2.8 (18.68)
Week 168; n=33	-4.9 (26.55)
Week 192; n=30	-1.2 (21.54)
Week 216; n=21	-0.8 (13.99)
Week 240; n=17	4.4 (12.33)
Week 264; n=7	2.7 (13.14)
Week 288; n=2	39.5 (54.45)

12. Secondary Outcome

Title	Change From Baseline in Erythema/Edema Score 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter
Description	The erythema subscale score and edema subscale score are each graded on a 0-3 scale, with 0 = absent , 1 = mild, 2 = moderate, 3 = severe. The total score ranged from 0 to 6, with higher scores indicative of more severe Erythema/Edema. The total score was obtained by summing together the responses for each of the two subscale items. Change from Baseline in erythema/edema total score is the difference between erythema/edema total score at the time point being analyzed to the MHE100901 Baseline score..
Time Frame	Baseline and up to approximately 6 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	78
Week 12; n= 59	0.0 (1.07)
Week 24; n= 54	0.0 (1.00)
Week 48; n= 36	0.0 (1.13)
Week 72; n=38	0.2 (0.98)
Week 96; n=21	-0.1 (1.01)
Week 120; n=11	-0.2 (0.60)
Week 144; n=9	-0.2 (0.67)
Week 168; n=6	0.5 (1.05)
Week 192; n=4	0.8 (0.96)
Week 216; n=4	0.3 (1.26)
Week 240; n=11	0.3 (0.65)
Week 264; n=8	0.0 (0.00)
Week 288; n=3	-1.0 (1.00)

13. Secondary Outcome

Title	Change From Baseline in Quality of Life (QoL) and Current Health Status: Physical Summary Score of the Study Short Form Health Survey (SF-12) 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter
Description	The SF-12v2 is the 12 item abbreviated form of SF-36v2 survey . It provides information about how participants feel, and how well they have been able to perform their usual activities, over the past 4 weeks. SF-12v2 questions make up 8 scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health . Transformed physical component summary score (PCS-12) is derived using all the 12 items and scored onto a 0-100 scale such that a higher score indicates a better health state and better functioning. Change from Baseline in scale or summary measure score is the difference between the score at the time point being analyzed to Baseline.
Time Frame	Baseline and up to approximately 6 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	75
Week 12; n= 64	-2.0 (8.25)
Week 36; n= 50	-1.4 (8.76)
Week 60; n=48	-1.1 (8.91)
Week 84; n=47	-0.8 (8.43)
Week 108; n=39	-1.0 (8.23)
Week 132; n=37	-1.3 (8.33)
Week 156; n=41	-1.1 (8.66)
Week 180; n=45	-2.1 (8.10)
Week 204; n=43	-2.2 (10.02)
Week 228; n=44	-0.1 (9.41)
Week 252; n=24	-1.3 (9.60)
Week 276; n=12	-1.4 (10.76)

14. Secondary Outcome

Title	Change From Baseline in QoL and Current Health Status: Mental Summary Score of the SF12 3 Months After the Start of Study MHE100901 and Every 6 Months Thereafter
Description	The SF-12v2 is the 12 item abbreviated form of SF-36v2 survey developed by the Medical Outcomes Trust and QualityMetric Incorporated. It provides information about how participants feel, and how well they have been able to perform their usual activities, over the past 4 weeks. SF-12v2 scale questions make up 8 scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health are for mental component summary. Transformed mental component summary score (MCS-12) is derived using all the 12 items and scored onto a 0-100 scale such that a higher score indicates a better health state and better functioning. Change from Baseline in scale or summary measure score is the difference between the score at the time point being analyzed to Baseline.
Time Frame	Baseline and up to approximately 6 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
Measure Participants	75
Week 12; n= 64	2.8 (8.46)
Week 36; n= 50	1.6 (10.75)
Week 60; n=48	2.8 (10.34)
Week 84; n=47	1.5 (8.46)
Week 108; n=39	2.9 (11.02)
Week 132; n=37	5.3 (10.20)
Week 156; n=41	2.1 (10.82)
Week 180; n=45	2.7 (11.95)
Week 204; n=43	1.9 (11.54)
Week 228; n=44	1.8 (11.43)
Week 252; n=24	0.6 (12.13)
Week 276; n=12	3.3 (12.44)

Adverse Events

Time Frame	On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from from the first dose of study medication up to 7 days after the last dose (up to approximately 6 years).
Adverse Event Reporting Description	SAEs and non-serious AEs were collected in members of the Intent to treat (ITT)population, comprised of all enrolled participants who received at least one dose of mepolizumab in this study
Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received mepolizumab 750 mg by IV infusion monthly in Stage 1 along with concomitant HES-active medications that included prednisone (or equivalent) or other HES therapies. In Stage 2, the dosing intervals were optimized for each participant based on the individual's blood eosinophil count and the clinical presentation. In Stage 3, the dosing frequency established in Stage 2 was continued with individual participant monitoring.
All Cause Mortality
	Mepolizumab 750 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Mepolizumab 750 mg
	Affected / at Risk (%)	# Events
Total	40/78 (51.3%)
Blood and lymphatic system disorders
Eosinophilia	2/78 (2.6%)
Anaemia	1/78 (1.3%)
Autoimmune thrombocytopenia	1/78 (1.3%)
Hypereosinophilic syndrome	1/78 (1.3%)
Cardiac disorders
Cardiac failure	2/78 (2.6%)
Atrioventricular block	1/78 (1.3%)
Bradycardia	1/78 (1.3%)
Cardiac failure congestive	1/78 (1.3%)
Myocardial infarction	1/78 (1.3%)
Endocrine disorders
Adrenal insufficiency	1/78 (1.3%)
Gastrointestinal disorders
Diarrhoea	2/78 (2.6%)
Abdominal pain upper	1/78 (1.3%)
Gastritis	1/78 (1.3%)
Gastroenteritis eosinophilic	1/78 (1.3%)
Gastrooesophageal reflux disease	1/78 (1.3%)
Pancreatitis	1/78 (1.3%)
General disorders
Pyrexia	3/78 (3.8%)
Disease progression	1/78 (1.3%)
Fatigue	1/78 (1.3%)
Influenza like illness	1/78 (1.3%)
Multi-organ failure	1/78 (1.3%)
Sudden death	1/78 (1.3%)
Hepatobiliary disorders
Cholecystitis acute	2/78 (2.6%)
Cholangitis sclerosing	1/78 (1.3%)
Infections and infestations
Pneumonia	4/78 (5.1%)
Acquired immunodeficiency syndrome	1/78 (1.3%)
Bronchiectasis	1/78 (1.3%)
Bronchitis	1/78 (1.3%)
Device related infection	1/78 (1.3%)
Gastroenteritis	1/78 (1.3%)
Gastroenteritis clostridial	1/78 (1.3%)
HIV infection	1/78 (1.3%)
Herpes zoster	1/78 (1.3%)
Influenza	1/78 (1.3%)
Lobar pneumonia	1/78 (1.3%)
Pneumocystis jiroveci pneumonia	1/78 (1.3%)
Post procedural infection	1/78 (1.3%)
Sepsis	1/78 (1.3%)
Upper respiratory tract infection	1/78 (1.3%)
Thermal burn	1/78 (1.3%)
Swelling face	1/78 (1.3%)
Injury, poisoning and procedural complications
Accidental overdose	1/78 (1.3%)
Hip fracture	1/78 (1.3%)
Splenic rupture	1/78 (1.3%)
Investigations
Hepatic enzyme increased	1/78 (1.3%)
T-lymphocyte count increased	1/78 (1.3%)
Metabolism and nutrition disorders
Calciphylaxis	1/78 (1.3%)
Dehydration	1/78 (1.3%)
Hypoglycaemia	1/78 (1.3%)
Hypokalaemia	1/78 (1.3%)
Musculoskeletal and connective tissue disorders
Spinal disorder	1/78 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	2/78 (2.6%)
Angioimmunoblastic T-cell lymphoma	1/78 (1.3%)
Hepatic neoplasm	1/78 (1.3%)
Multiple myeloma	1/78 (1.3%)
Nervous system disorders
Cervicobrachial syndrome	1/78 (1.3%)
Haemorrhage intracranial	1/78 (1.3%)
Ischaemic stroke	1/78 (1.3%)
Migraine	1/78 (1.3%)
Motor neurone disease	1/78 (1.3%)
Myelitis transverse	1/78 (1.3%)
Optic neuritis	1/78 (1.3%)
Radiculitis brachial	1/78 (1.3%)
Psychiatric disorders
Depression	1/78 (1.3%)
Self-injurious ideation	1/78 (1.3%)
Renal and urinary disorders
Nephrotic syndrome	1/78 (1.3%)
Renal colic	1/78 (1.3%)
Renal failure	1/78 (1.3%)
Renal failure acute	1/78 (1.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/78 (2.6%)
Asthma	1/78 (1.3%)
Nasal polyps	1/78 (1.3%)
Pulmonary fibrosis	1/78 (1.3%)
Respiratory arrest	1/78 (1.3%)
Rhinitis hypertrophic	1/78 (1.3%)
Status asthmaticus	1/78 (1.3%)
Skin and subcutaneous tissue disorders
Eczema	1/78 (1.3%)
Eosinophilic cellulitis	1/78 (1.3%)
Skin erosion	1/78 (1.3%)
Vascular disorders
Arterial occlusive disease	1/78 (1.3%)
Extremity necrosis	1/78 (1.3%)
Hypertension	1/78 (1.3%)
Hypotension	1/78 (1.3%)
Temporal arteritis	1/78 (1.3%)
Thrombophlebitis	1/78 (1.3%)
Other (Not Including Serious) Adverse Events
	Mepolizumab 750 mg
	Affected / at Risk (%)	# Events
Total	72/78 (92.3%)
Blood and lymphatic system disorders
Hypereosinophilic syndrome	7/78 (9%)
Anaemia	6/78 (7.7%)
Thrombocytopenia	5/78 (6.4%)
Cardiac disorders
Palpitations	5/78 (6.4%)
Eye disorders
Vision blurred	4/78 (5.1%)
Gastrointestinal disorders
Nausea	18/78 (23.1%)
Abdominal pain	17/78 (21.8%)
Diarrhoea	17/78 (21.8%)
Vomiting	10/78 (12.8%)
Abdominal pain upper	8/78 (10.3%)
Dyspepsia	8/78 (10.3%)
Abdominal discomfort	7/78 (9%)
Gastrooesophageal reflux disease	6/78 (7.7%)
Constipation	4/78 (5.1%)
Gastritis	4/78 (5.1%)
Oesophagitis	4/78 (5.1%)
Toothache	4/78 (5.1%)
General disorders
Fatigue	23/78 (29.5%)
Pyrexia	14/78 (17.9%)
Influenza like illness	10/78 (12.8%)
Pain	10/78 (12.8%)
Oedema peripheral	9/78 (11.5%)
Chest pain	8/78 (10.3%)
Oedema	7/78 (9%)
Asthenia	5/78 (6.4%)
Local swelling	4/78 (5.1%)
Infections and infestations
Rhinitis	9/78 (11.5%)
Ear infection	7/78 (9%)
Gastroenteritis	6/78 (7.7%)
Pharyngitis	6/78 (7.7%)
Urinary tract infection	6/78 (7.7%)
Cystitis	5/78 (6.4%)
Gastroenteritis viral	5/78 (6.4%)
Herpes zoster	5/78 (6.4%)
Localised infection	5/78 (6.4%)
Respiratory tract infection	5/78 (6.4%)
Fungal infection	4/78 (5.1%)
Influenza	4/78 (5.1%)
Pneumonia	4/78 (5.1%)
Injury, poisoning and procedural complications
Contusion	6/78 (7.7%)
Investigations
Weight decreased	7/78 (9%)
Metabolism and nutrition disorders
Decreased appetite	7/78 (9%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/78 (24.4%)
Back pain	16/78 (20.5%)
Pain in extremity	13/78 (16.7%)
Myalgia	11/78 (14.1%)
Muscle spasms	9/78 (11.5%)
Neck pain	5/78 (6.4%)
Nervous system disorders
Headache	23/78 (29.5%)
Hypoaesthesia	12/78 (15.4%)
Dizziness	9/78 (11.5%)
Paraesthesia	6/78 (7.7%)
Psychiatric disorders
Anxiety	9/78 (11.5%)
Insomnia	6/78 (7.7%)
Depression	5/78 (6.4%)
Respiratory, thoracic and mediastinal disorders
Sinusitis	22/78 (28.2%)
Upper respiratory tract infection	22/78 (28.2%)
Bronchitis	21/78 (26.9%)
Nasopharyngitis	18/78 (23.1%)
Cough	26/78 (33.3%)
Dyspnoea	17/78 (21.8%)
Asthma	11/78 (14.1%)
Oropharyngeal pain	11/78 (14.1%)
Epistaxis	6/78 (7.7%)
Rhinorrhoea	6/78 (7.7%)
Nasal congestion	5/78 (6.4%)
Sinus congestion	5/78 (6.4%)
Wheezing	4/78 (5.1%)
Skin and subcutaneous tissue disorders
Rash	17/78 (21.8%)
Pruritus	15/78 (19.2%)
Urticaria	13/78 (16.7%)
Erythema	6/78 (7.7%)
Night sweats	5/78 (6.4%)
Vascular disorders
Hypotension	4/78 (5.1%)

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.