A Study to Evaluate the Safety and Effectiveness of Epoetin Alfa in AIDS Patients With Anemia Caused Both by Their Disease and by AZT (Zidovudine, an Antiviral Drug) Given as Treatment for Their Disease

A Double-Blind, Placebo-Controlled Study With Open-Label Follow-up to Determine the Safety and Efficacy of r-HuEPO in AIDS Patients With Anemia Induced by Their Disease and AZT Therapy

The purpose of this study is to evaluate the effectiveness and safety of epoetin alfa versus placebo for the treatment of anemia in AIDS (Acquired Immunodeficiency Syndrome) patients with anemia that is a result of this disease and zidovudine (AZT) treatment. Epoetin alfa is a genetically engineered protein that stimulates red blood cell production.

It is estimated that approximately 75% to 80% of patients with AIDS experience anemia, which can be caused by AIDS or by the therapy patients receive for AIDS treatment (for example, AZT). Anemia is a condition in which a patient has below normal levels of hemoglobin, the substance in red blood cells that carries oxygen to all parts of the body. People with severe anemia may experience fatigue and shortness of breath with activity. Therefore, this condition can have a negative influence on a person's quality of life. Epoetin alfa, used to treat anemia, is a genetically engineered form of a natural hormone, erythropoietin, that stimulates red blood cell production. This is a randomized, double-blind, placebo-controlled, parallel group study with an open-label follow-up period that is designed to evaluate the safety and effectiveness of epoetin alfa treatment in patients with AIDS who are being treated with AZT. The study consists of 3 periods: a screening period to determine if patients are eligible for the study, a double-blind period, and an open-label period. Eligible patients will be randomly assigned to one of two groups: a group receiving epoetin alfa 100 U/kg or a group receiving matching placebo. Patients will be treated with study medication injected under the skin 3 times per week for 12 weeks (or until their hematocrit reaches 38% to 40%). In the open-label period, all patients receive epoetin alfa injected under the skin for up to 6 months. Effectiveness will be determined by the change in hemoglobin, hematocrit, and reticulocytes (laboratory tests used to evaluate the severity of anemia), transfusion requirements, the patient's quality of life assessment, and the physician's global evaluation of the drug effect. Safety assessments include the incidence and severity of adverse events during the study, and changes in clinical laboratory tests (hematology, biochemistry, and urinalysis), vital signs, electrocardiograms (ECGs), and physical examination findings. The study hypothesis is that AIDS patients who are receiving AZT and who are treated with epoetin alfa will have a lower incident of anemia compared with patients receiving placebo. Double-blind: epoetin alfa (100 U/kg) or placebo given under the skin 3 times a week for 12 weeks or until hematocrit reaches 38% to 40%. Open-label: epoetin alfa 150 U/kg 3 times a week for up to 6 months (once weekly after hematocrit reaches 38% to 40%). Dosage may be adjusted up to 300 U/kg.

Inclusion Criteria:

• Patients with a confirmed diagnosis of AIDS, exhibiting signs and symptoms of AIDS characterized by lymphocytopenia (decrease in the number of lymphocytes in the blood) as determined by a finding of <1,000 cells/cubic millimeter and a documented (if available) decrease in CD4 (a protein found on certain cells that has an affinity for the HIV virus) positive lymphocytes as determined by a finding of <400 cells/cubic millimeter
• presence of HIV antibody
• documented history of infection (such as pneumonia) resulting from the patient's impaired resistance
• hematocrit <=30%, and a history of a >=15% decrease in hematocrit since starting AZT therapy, or that the patient has become dependent on transfusions
• clinically stable for >=1 month before study entry, with a performance score of 0, 1, or 2.

Exclusion Criteria:

• Patients with a history of any important blood disease, or clinically significant disease or malfunction of the lungs, heart, hormones, neurological, gastrointestinal, reproductive or urinary systems, which are not caused by the AIDS infection
• having anemia caused by other conditions than AIDS or AZT therapy (for example, certain vitamin deficiencies or bleeding from the gastrointestinal tract)
• having a sudden onset of infections, dementia due to AIDS, uncontrolled high blood pressure, or an iron deficiency
• having a history of seizures, history of cell damage due to chemotherapy within 1 month before study entry, or a history of substance abuse
• received androgen therapy within 2 months before study entry