Open-Label Extension Of Intravenous Mepolizumab In Patients With Hypereosinophilic Syndrome
- Registration Number
- NCT00097370
- Lead Sponsor
- GlaxoSmithKline
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 78
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description mepolizumab mepolizumab 750mg Intravenous, monthly and individual dosing schedule
- Primary Outcome Measures
Name Time Method 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
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
Name Time Method 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.
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).
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.
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).
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).
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)
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.
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.
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.
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..
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.
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.
Trial Locations
- Locations (1)
GSK Investigational Site
🇮🇹Bologna, Emilia-Romagna, Italy