Safety and Effectiveness of CD4-IgG2 in HIV-Positive Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      CD4-IgG2 is a special man-made protein that was built to block the entrance of HIV into CD4
      cells (cells of the immune system that fight infection). The purpose of this study is to see
      if giving CD4-IgG2 to HIV-infected children is safe and effective.

      HIV attaches to CD4 cells and enters them. Inside, HIV makes copies of itself that will help
      the virus invade the body. CD4 cells are killed or disabled during this process of HIV
      replication. Decreases in CD4 cells lead to a weakened immune system. When CD4 cell counts
      become very low, the body is unable to defend itself, and HIV infection develops into AIDS.
      The protein used in this study, CD4-IgG2, may be able to attach to HIV and inactivate it so
      that it cannot enter CD4 cells. This is an early study to examine CD4-IgG2 as a possible
      treatment for HIV in children.
    

Detailed description: 
      Since CD4 is the high-affinity receptor for HIV-1, molecules such as CD4-IgG2, which
      incorporate the gp120 binding region of CD4, have the potential to bind and neutralize all
      strains of the virus. [AS PER AMENDMENT 4/25/00: Study results have demonstrated that the
      product is safe in children, well tolerated, and may have antiviral properties. With these
      encouraging results in hand, an extra cohort has been added using twice the dose of rCD4-IgG2
      as in Cohort I.]

      The study is conducted in two parts. In Part 1 patients receive a single dose of CD4-IgG2
      intravenously at 1 of 4 dose levels. A minimum of 3 patients are treated at a given dose
      level. If none of these 3 patients experience Grade 3 or 4 toxicity, patients are escalated
      to the next dose level. If any of these 3 patients have life-threatening toxicities or if
      more than 1 of these 3 patients experience non-life-threatening Grade 3 or 4 toxicities,
      escalation stops and the prior dose (if any) is considered the maximum tolerated dose (MTD).
      If 1 of these 3 patients experiences non-life-threatening Grade 3 or 4 toxicities, 3
      additional patients are treated at this dose level. If 1 or more of these 3 additional
      patients has Grade 3 or 4 toxicity, escalation stops. If none of these 3 additional patients
      has Grade 3 or 4 toxicity, patients are escalated to the next dose level.

      Part 2 provides additional data on the safety, toxicity and pharmacokinetics of CD4-IgG2 when
      given in multiple doses. Patients receive the highest safe dose (MTD) as established in Part
      1. Treatment is given intravenously once weekly at Weeks 0, 1, 2, and 3. If insufficient
      activity is seen at this dose level, 6 additional patients will be enrolled at a higher dose
      level. Patients who participate in Part 1 may enroll in Part 2 provided they are followed for
      at least 3 months and meet inclusion criteria for Part 2. If any patient experiences a
      life-threatening condition due to CD4-IgG2, the study will stop. [AS PER AMENDMENT 4/25/00:
      Cohort II receives twice the dose of Cohort I intravenously once weekly at Weeks 0, 1, 2 and
      3. Pharmacokinetic samples are obtained at pre-dose and 1 hour after the doses are
      administered at Weeks 0, 1, and 2; and pre-dose, 1 hour, 24 hours, and Days 3, 7, and 14
      after the dose are administered at Week 3. An overnight stay in the hospital is recommended
      for the first 24 hours. At Weeks 0, 1, 2, and 3, virology testing including HIV-1 RNA is
      performed with each infusion of CD4-IgG. Follow-up monitoring of patients is done once a
      month for 4 months for patients in Cohort II.]
    

Intervention name(s): CD4-IgG2
Intervention type(s): Drug
Intervention MeSH terms: CD4 Immunoadhesins
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Antiviral Agents; CD4-IgG(2); PRO 542