B-Lymphocyte Stimulator (BLyS) To Treat Selective IgA Deficiency

• Status: Completed
• Trial end date: 2004-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will examine the safety of BlyS, an experimental drug being developed to treat immune deficiency. As of July 17, 2001, 7 persons with common variable immune deficiency (CVID) have received BlyS, with no problems reported. This study will test the safety of the drug in people with IgA deficiency.

Patients 18 years of age and older with IgA deficiency who have recurrent or chronic sinus or lung infections or chronic diarrhea or malabsorption may be eligible for this study. Candidates will be screened with a physical examination, blood and urine tests, electrocardiogram (EKG), chest X-ray and a breathing test (spirometry).

Participants will be divided into five groups of three persons each to receive different doses (0.1, 1, 5, 15 or 45 micrograms/kilogram of body weight) of BlyS. The first group will receive a single dose at the lowest dose level (0.l mg). Each succeeding group will receive a single higher dose following a 2-week observation period of the preceding group. The drug will be injected under the skin, with vital signs (temperature, pulse, blood pressure and breathing rate) monitored for one hour after dosing. Blood samples will be collected several times on the day of dosing (before the dose and at 1.5, 3, 5, 8 and 12 hours after the dose) and again at 1,2, 4, 8 and 12 weeks after the dose to measure BlyS levels and evaluate safety. Participants receiving one of the three higher doses will have additional blood samples collected 36, 48 and 60 hours after the dose. Blood will also be collected from all participants 6 and 12 months after dosing to look for any unexpected long-term effects. A total of 289 ml (1.2 cups) of blood will be collected.

Blood will be checked for changes in blood count, kidney and liver function, antibody levels and autoimmune problems. Saliva will be collected four times by placing a cotton ball in the mouth-once before the dose and three times after the dose-to measure antibody levels.

Urine samples will also be collected during the study.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)

Criteria

INCLUSION CRITERIA:

Eligible subjects must meet the diagnostic criteria for IgA deficiency as defined by WHO or PAGID/ESID (Conley, 1999).

Diagnosis of IgA-D with recurrent or chronic sinopulmonary infection or chronic diarrhea/malabsorption.

Serum IgA at least 2 standard deviations below the mean at screening.

Eligible patients will be at least 18 years of age.

Liver function tests (SGOT, SGPT, alkaline phosphatase, total bilirubin) within 1.25 x upper limit of normal.

Serum creatinine within normal limits.

Patients must be able to understand and sign an informed consent form.

EXCLUSION CRITERIA:

A history of malignancy (other than adequately treated in situ carcinoma or non-melanotic skin cancer).

Active clinically-significant autoimmune manifestations within 2 years of study entry; any history of IgA nephropathy or Henoch-Schonlein purpura.

Pre-existing renal disease; proteinuria greater than trace at screening.

Symptomatic cardiac disease (greater than grade 1 NCI CTC) at screening. Patients with adequately treated well-controlled hypertension or minor arrythmias are eligible.

Pulmonary disease requiring treatment, bronchiectasis on baseline chest x-ray or FEV1 less than 75% normal limits at baseline evaluation. Patients with adequately treated well-controlled asthma are eligible.

Splenomegaly associated with cytopenias.

Significant cytopenias: Anemia (Hct less than 30%); Neutropenia (ANC less than 1500/microL); Thrombocytopenia (Platelets less than 75,000/mm(3)).

Biopsy-proven granulomatous disease.

B-lymphocyte count at screening less than 50/microL.

Use immune-based therapies (other than IVIG) such as chronic corticosteroid use, growth factors or other immune-modulating drugs within 4 weeks of screening (inhaled corticosteroids are permitted).

Pregnant female or nursing mother. (All females of childbearing potential must have had a negative blood or urine pregnancy test at screening. Over the course of the study, all female subjects must have practiced a method of contraception with greater than 90% reliability, or be sterile or postmenopausal.)

Participation in any clinical trial involving investigational or conventional drugs within 30 days of screening.

Known active hepatitis (testing not required for study entry).