Trial Information

A Phase I Study of the Safety and Pharmacokinetics of Recombinant Human CD4-Immunoglobulin G (rCD4-IgG) Administered by Intravenous Bolus Injection in Combination With Oral Zidovudine in Patients With AIDS and AIDS-Related Complex

Treatment of AIDS has been directed toward the underlying retroviral infection as well as
toward specific opportunistic infections and malignancies that are associated with the
syndrome. The most extensively studied drugs are reverse transcriptase inhibitors such as
AZT and other nucleoside analogs, including didanosine (ddI) and dideoxycytidine (ddC). The
most extensive clinical experience has been achieved with AZT. These clinical trials
indicated a decreased incidence of opportunistic infection and increased survival in
patients with AIDS. However, AZT treatment is associated with dose-limiting toxicities.
Additionally, identification of resistance to AZT has increased the need to test the
effectiveness of AZT in combination with other drugs. CD4-IgG is capable of binding to HIV
envelope protein (gp120) and inhibiting HIV infectivity in test tube studies. Potential
therapeutic benefit in patients with HIV infection may be derived from CD4-IgG.

AMENDED: Previously, rCD4-IgG had been administered on a mcg/kg basis. Subjects now receive
rCD4-IgG as a fixed dose. Changes to the maintenance schedule were made to accommodate the
new dosages. Original design: This study is divided into two parts: A pharmacokinetic
evaluation, and a safety evaluation. The pharmacokinetic evaluation is done in selected
patients. For the safety evaluation patients will receive rCD4-IgG at a fixed dose level
twice weekly by intravenous bolus injection (over 1 minute) for 12 weeks. Zidovudine (AZT)
is administered orally 3 times daily at one of two dose levels. Eight subjects, at least 4
of whom with p24 levels greater than 75 pg/m, are entered at each dose level of CD4-IgG
beginning with dose level 1. If 3 or more patients at a dose level experience grade 3 or 4
toxicity then no further patients will be added to that or higher dose levels.
Pharmacokinetics of CD4-IgG alone and in combination with AZT is evaluated in patients at
dose level 2 only. Patients receive one IV bolus of CD4-IgG on day 1 and samples are drawn
beginning 15-30 minutes prior to the CD4-IgG injection. There is an 8 day washout period.
Beginning on day 9 and continuing through day 24, patients receive AZT daily. CD4-IgG is
administered by IV bolus on day 16. Samples are drawn beginning 15-30 minutes prior to the
injection of CD4-IgG. The pharmacokinetic evaluation terminates 8 days after the second
CD4-IgG injection (day 24). Extended treatment will be made available to patients at the
discretion of the Principal Investigator.