104317: The market authorisation application for mepolizumab for the indication ofhypereosinophilic syndrome (HES) was filed in 2008, but later the file was withdrawn dueto outstanding questions from regulator's raised from the application. On the basis ofsponsor's evaluation, participants with life-threatening HES who have documented failure(lack of efficacy or a contra-indication) to at least 3 standard HES therapies(compassionate use) and participants who have participated in a previous GSK sponsoredstudy in HES (long-term access) can be consider for mepolizumab treatment where thecountry regulation permits. In this study, participants will receive mepolizumab in anopen-labelled manner, and limited data will be collected to evaluate the long-term safetyand efficacy of mepolizumab.201956: This is a Long-term Access Programme (LAP) which aims to support provision ofmepolizumab, until it is commercially available, to eligible subjects with severe asthmawho participated in a GSK-sponsored mepolizumab clinical study in severe asthma. Eligiblesubjects will initiate mepolizumab within a 6-month period following the individualsubject's last scheduled visit in their preceding clinical study. For each subjectbenefit versus risk will be assessed throughout the study to support continued treatmentwith mepolizumab.112562: To provide a mechanism for expanded access to mepolizumab therapy for eligiblepatients with HES. Whenever possible, use of an investigational medicinal product by apatient as part of a clinical trial is preferable. However, when patient enrollment in aclinical trial is not possible (such as when the patient is not eligible for ongoingclinical trials or the patient is not able to attend investigational sites), appropriatepatients may receive mepolizumab through expanded access. This expanded access protocolwas designed to allow access to mepolizumab for HES patients with seriously debilitatingor life-threatening disease that are not able to enroll in clinical trials, includingthose patients that have already participated in a mepolizumab clinical trial.
Drug: Mepolizumab
open label investigational product
104317 Inclusion criteria:
- ≥ 12 years of age
- Has life-threatening HES as defined by the treating physician's documented view that
likelihood of death is high unless the course of the disease is interrupted.
- Meets the diagnostic criteria for Hyper Eosinophilic Syndrome as defined by:
Eosinophilia >1500cells/ul for at least 6 months with evidence of symptoms and signs of
organ system involvement or dysfunction that can be directly related to eosinophilia
(with no evidence of parasitic, allergic or other recognized causes of eosinophilia such
as connective tissues disease, malignancy) or Eosinophilia of >1500cells/ul for less than
6 months who meet the other criteria for HES accompanied by clear evidence of eosinophil
tissue infiltration and with exclusion for secondary causes of eosinophilia as above.
- Compassionate use: Documented failure (lack of efficacy or a contra-indication) to
at least 3 standard therapies (corticosteroids, cytotoxic agents, immunomodulatory
therapy, and Imatinib mesylate) at the appropriate duration and dose
- Long-term access: Entry of subjects who participated in a previous GSK HES study to
this study must be supported by the following: Subjects who received mepolizumab (if
study treatment is known) in a previous GSK HES study: Documented improvement in
symptoms and/or signs of HES following treatment with mepolizumab or Subjects who
received mepolizumab or placebo in a previous GSK HES study: The treating physician
must confirm a positive benefit/risk ratio, and the anticipated clinical benefit
from mepolizumab must outweigh any potential safety or tolerability risk in this
study or Subjects who participated in Study 200622 should complete the protocol
required assessments for the duration of 32 weeks after randomization. Subsequently,
subjects should complete the 20-week assessments in Study 205203, open-label
extension (OLE) to Study 200622, prior to being considered for this protocol
(MHE104317). In addition, subjects should not have had an adverse event (serious or
non-serious) considered related to study treatment while participating in Study
200622 or Study 205203 which resulted in permanent withdrawal of study treatment.
104317 Exclusion Criteria:
- Subjects without HES but with other conditions associated with eosinophilic
pathological process such as Churg-Strauss, Wegner's Granulomatosis, atopic
disorders, hypersensitivity reactions to parasitic infections, eosinophilic
gastroenteropathies, will not be eligible for this compassionate use program which
is restricted to life-threatening HES.
- Female subjects of child -bearing potential who are not using an effective method of
contraception:
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 16 weeks after the last
dose.
- Pregnant or lactating females
- Subjects with severe/life-threatening underlying disease unrelated to HES unrelated
to HES where life expectancy is estimated to be less than 3 months.
- Subjects with a history of or current malignancy: Subjects with a history of or
current lymphoma or Subjects with current malignancy or previous history of cancer
in remission for less than 12 months prior to the first dose. Subjects that had
localized carcinoma (i.e., basal or squamous cell) of the skin which was resected
for cure will not be excluded.
- Subjects with history of serious allergic reaction (hypersensitivity/anaphylaxis) to
anti-IL5 or other antibody therapy or known or suspected hypersensitivity to any
component of mepolizumab, leading to treatment discontinuation
- Subjects with current drug or alcohol abuse where uncertain compliance with
medication causes safety risk.
- subject currently receiving any other investigational product or other
investigational intervention.
201956 Inclusion criteria:
- Subject participated in GSK-sponsored asthma clinical study with mepolizumab.
- Subject has either: completed the treatment period in the mepolizumab asthma
clinical study to which they were originally enrolled or if the subject was
withdrawn from study treatment prematurely during the mepolizumab asthma clinical
study to which they were originally enrolled but the subject has completed the study
assessments at the study visit that would have been the end of the respective
treatment period.
- The treating physician requesting mepolizumab under this Long-term Access Programme
considers the benefits of treatment with mepolizumab outweigh the risks for the
individual subject.
- To be eligible for mepolizumab treatment under this Long-term Access Programme,
females of childbearing potential (FCBP) must commit to consistent and correct use
of an acceptable method of birth control, beginning with consent, for the duration
of the treatment with mepolizumab and for 4 months after the last mepolizumab
administration.
- The subject consents to receiving treatment with mepolizumab under this Long-term
Access Programme. In the case of a paediatric subject being eligible a
parent(s)/guardian will give written informed consent prior to the child's
participation in the study. If applicable, the subject must be able and willing to
give assent to take part in the study according to the local requirement.
201956 Exclusion criteria:
- A current malignancy or history of cancer in remission for less than 12 months
(Subjects who had localized carcinoma (i.e., basal or squamous cell) of the skin
which was resected for cure will not be excluded).
- Subject has other clinically significant medical conditions uncontrolled with
standard-of-care therapy not associated with asthma, e.g., unstable liver disease,
uncontrolled cardiovascular disease, ongoing active infectious disease requiring
systemic treatment.
- Subject is pregnant or breastfeeding. Subjects should not be considered for
continued treatment if they plan to become pregnant during the course of treatment
with mepolizumab.
- Subject has a known allergy or intolerance to a monoclonal antibody or biologic
therapy including mepolizumab.
- Subject had an adverse event (serious or non-serious) considered related to study
treatment whilst participating in a clinical study with mepolizumab which resulted
in permanent withdrawal of study treatment.
- Subject is receiving treatment with another biological therapy such as a monoclonal
antibody therapy or intravenous (IV) immunoglobulin (Ig) therapy.
- Subjects who have received treatment with an investigational drug within the past 30
days or 5 terminal phase half-lives of the drug whichever is longer, prior to
initiation of mepolizumab treatment under this Long-term Access Programme (this also
includes investigational formulations of marketed products).
- Subject is currently participating in any other interventional clinical study.
112562 Inclusion criteria:
- In accordance with local procedures, written informed consent/assent can be obtained
from the patient or legally authorized representative.
- ≥ 12 years of age at the time of signing the informed consent/assent.
- Meets the diagnostic criteria for HES as defined by:
Eosinophilia >1500 cells/µl for at least 6 months with evidence of symptoms and signs of
organ system involvement or dysfunction that can be directly related to eosinophilia
(with no evidence of parasitic, allergic or other recognised causes of eosinophilia such
as connective tissues disease, malignancy) or Eosinophilia of >1500 cells/µl for less
than 6 months and meet the other criteria for HES accompanied by clear evidence of
eosinophil tissue infiltration and with exclusion of secondary causes of eosinophilia as
above.
- Patients meeting all three of the following criteria will be eligible: The
indication, HES, is a seriously debilitating or life-threatening disease; There is
no satisfactory alternative treatment: documented failure (lack of efficacy or a
contra-indication) to at least 3 standard therapies (corticosteroids, cytotoxic
agents, immunomodulatory therapy, and Imatinib mesylate) at the appropriate duration
and dose or demonstrated clinical benefit from prior treatment with mepolizumab; and
There is reason to believe that the benefit:risk ratio for mepolizumab in the
indication is positive.
112562 Exclusion criteria:
- Patients without HES but with other conditions associated with eosinophilic
pathological processes such as eosinophilic granulomatosis with polyangiitis [EGPA],
Wegener's granulomatosis, atopic disorders, parasitic infections, eosinophilic
gastroenteropathies.
- Female patients of childbearing potential who are not using an effective method of
contraception:
Consistent and correct use of an acceptable method of birth control for one month prior
to the start of the investigational medicine and until 16 weeks after the last dose (see
Appendix 3 for a list of acceptable methods of contraception).
- Pregnant or lactating females
- Patients with severe/life-threatening underlying disease unrelated to HES where life
expectancy is estimated to be less than 3 months
- Patients with a history of or current malignancy:
- Patients with a history of or current lymphoma
- Patients with current malignancy or previous history of cancer in remission for less
than 12 months prior to the first dose. Patients that had localized carcinoma (i.e.,
basal or squamous cell) of the skin which was resected for cure will not be
excluded.
- Patients with history of serious allergic reaction (hypersensitivity/anaphylaxis) to
anti-IL5 or other antibody therapy or known or suspected hypersensitivity to any
component of mepolizumab, leading to treatment discontinuation
- Patients with current drug or alcohol abuse where uncertain compliance with the
protocol and/or with the medical management instruction of the treating physician
may cause safety risk
- Patients who have received treatment with an investigational agent (biologic or
non-biologic, excluding mepolizumab) within the past 30 days or 5 drug half-lives
whichever is longer, prior to the administration of mepolizumab under this protocol.
The term "investigational" applies to any drug not approved for sale in the country
in which it is being used or investigational formulations of marketed products.
GSK Clinical Trials, Study Director
GlaxoSmithKline