Intravenous Mepolizumab In Subjects With Hypereosinophilic Syndromes (HES)

Study Overview
=================
Brief Summary
-----------------
Hypereosinophilic syndrome (HES) is a rare disease with broad clinical signs and symptoms which is diagnosed based on a persistent blood eosinophil count of greater than 1500 cells, various end-organ damages (including skin, heart, lung, nervous system and digestive system etc.), and with exclusion of known secondary causes of hypereosinophilia. HES has a high morbidity/mortality rate. The major treatment of HES has been systemic corticosteroid and other chemotherapeutic drugs (for example, hydroxyurea and interferon) with the intention to lower eosinophil counts and therefore to slow down the progression of disease. Even though corticosteroid and other therapies can effectively reduce eosinophilia in some patients, some may eventually become nonresponsive and intolerable to the amount of side effects of the long-term therapy with these medications. Mepolizumab is a humanized monoclonal antibody that binds specifically to human interleukin 5 (hIL-5) and inhibits its activity. Previous human experience has shown it has been effective in reducing blood eosinophilia in atopic and HES patients and has alleviated some HES clinical signs and symptoms. This study intends to further evaluate the corticosteroid-sparing and clinical benefit of mepolizumab in HES.

Detailed Description
-----------------
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Phase III Study to Evaluate Corticosteroid-reduction and -sparing effects of Mepolizumab 750 mg intravenously in Subjects with Hypereosinophilic Syndromes (HES) and to evaluate the Efficacy and Safety of Mepolizumab in controlling the Clinical Signs and Symptoms of HES over Nine Months

Official Title
-----------------
A Multicenter, Double-blind, Placebo-controlled, Study to to Evaluate the Corticosteroid- Sparing Effects of Mepolizumab in Subjects With Hypereosinophilic Syndromes (HES) and Evaluate Efficacy and Safety of Mepolizumab in Controlling the Clinical Signs and Symptoms of Subjects With HES

Conditions
-----------------
Hypereosinophilia, Hypereosinophilic Syndrome

Intervention / Treatment
-----------------
* Drug: mepolizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Documented history of Hypereosinophilic Syndrome (HES) Eosinophil count greater than 1500 cells for 6 months Signs and symptoms of organ system involvement No evidence of parasitic, allergic or other causes of eosinophilia after comprehensive evaluation. Achieve and maintain a stable prednisone (corticosteroid) dose prior to starting study medication. Not pregnant or nursing. Exclusion criteria: Churg-Strauss Syndrome Wegener's Granulomatosis Lymphoma, hematological malignancy, advanced and metastatic solid tumors Chemotherapy, radiotherapy or interleukin 2 treatment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: mepolizumab|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve a total daily prednisone dose of </=10 mg for a period of 8 consecutive weeks |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the effect of mepo in lowering prednisone dose and blood eosinophil count, improving HES-associated skin manifestations, improving quality of life (QoL), safety and tolerability. |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypereosinophilic Syndrome Hypereosinophilia, mepolizumab, anti IL-5