Protocol Number: 04-I-0158

Title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Phase III Study to Evaluate Corticosteroid-Reduction and -Sparing Effects of Mepolizumab 750 mg Intravenous in Subjects with Hypereosinophilic Syndromes (HES), and to evaluate the

Number:

04-I-0158

Summary:

This study will examine the safety and effectiveness of the drug mepolizumab for treating patients with hypereosinophilic syndrome (HES), a disease in which patients have too many eosinophils (a type of white blood cell) in the blood and in body tissues. This causes damage to affected organs, most commonly the heart, nerves and skin. Mepolizumab is a genetically engineered antibody to interleukin 5, a hormone-like substance produced by white blood cells that plays a significant role in eosinophilia.

Patients with HES between 18 and 75 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination, electrocardiogram, and blood tests.

Participants are treated with prednisone or another corticosteroid for 1 to 6 weeks while they gradually stop taking all other medications for HES. Patients whose disease is controlled successfully with 20 to 50 mg of prednisone a day (or the equivalent) for 1 week may continue in the study. They undergo a baseline evaluation, including physical, neurological and skin exams, a skin biopsy if skin lesions are present, blood and urine tests, electrocardiogram (ECG), echocardiogram, esophagogastroduodenoscopy (EGD, a procedure in which a tube-like instrument is advanced from the throat to the upper part of the gut to examine the gastrointestinal tract), CT scans of the sinuses, lungs, and abdomen, and quality of life assessments.

Patients are then randomly assigned to receive an infusion by vein every 4 weeks of either mepolizumab or placebo (a substance that contains no active drug) for 36 weeks. One week after beginning the study drug, patients' prednisone dose is gradually reduced until it is stopped. Patients are followed weekly for the first 12 weeks by NIH physicians or by the patient's local physician as well as every 4 weeks throughout the study at NIH until treatment is complete. Patients undergo the following tests and procedures during the treatment period:

- History, physical examination, and skin assessments: every 4 weeks.

- Neurologic exam: weeks 4, 8, 16, and 36 (or at the patient's final visit if earlier than 36 weeks).

- Blood tests: chemistries and hematology every week for 12 weeks and then every 4 weeks until the end of the study; measurements of mepolizumab levels at weeks 1, 2, 3, 4, 8, 16, 24, 32 and the end of the study; tests to detect antibodies against mepolizumab every 12 weeks.

- ECG: every 8 weeks.

- Echocardiogram and lung function tests: week 16 and the end of the study.

- CT scans of parts of the body affected by HES: at the end of the study.

- EGD: week 16 and the end of the study if there are gastrointestinal signs and symptoms thought to be related to HES.

- Urine collection: every 4 weeks for pregnancy test in women of childbearing potential; urinalysis at week 12 and the end of the study.

- Questionnaires to assess physical and mental condition: every 12 weeks

During the study, patients' symptoms are treated with prednisone or another corticosteroid. Those who require other medications to control symptoms are taken off the study. Patients are contacted three months after their last dose of drug upon completing or withdrawing from the study to check on possible adverse events and for a final urine pregnancy test in women.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): Children

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Eosinophil

Monoclonal Antibody

Treatment

Recruitment Keyword(s):

Eosinophil

Hyperesosinophilic Syndrome

HES

Condition(s):

Hypereosinophilic Syndrome

Investigational Drug(s):

SB-240563 (mepolizumab)

Investigational Device(s):

None

Interventions:

Drug: SB-240563 (mepolizumab)

Supporting Site:

National Institute of Allergy and Infectious Diseases

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Cardon LR, et al. Testing drug response in the presence of genetic information: sampling issues for clinical trials. Pharmacogenetics. 2000 Aug;10(6):503-10. PMID: 10975604

Arranz M, et al. Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet. 1995 Jul 29;346(8970):281-2. PMID: 7630250

Daly AK. Molecular basis of polymorphic drug metabolism. J Mol Med. 1995 Nov;73(11):539-53. Review. PMID: 8751138

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

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