Study of a New Anti-HIV Drug, T-20, in HIV-Infected Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine the best dose of T-20, a new anti-HIV drug, to
      treat HIV-infected children.

      T-20, unlike other anti-HIV medications, lessens the ability of HIV to infect certain cells
      (T cells) in the body. Doctors hope to better treat HIV by adding T-20 to anti-HIV drug
      combinations that include 1 or 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a
      nonnucleoside reverse transcriptase inhibitor (NNRTI) and/or a protease inhibitor (PI).
    

Detailed description: 
      T-20 is the first drug to be developed which specifically inhibits the function of the gp41
      transmembrane glycoprotein. By inhibiting the essential protein-protein surface interaction,
      T-20 is able to block the process of virus-to-host cell membrane fusion. Combination
      antiretroviral regimens (reverse transcriptase inhibitors plus PIs) have benefited many HIV
      patients, but heavily pretreated patients often develop multi-drug resistance via multiple
      gene mutations. A pharmacologic agent, such as T-20, that is effective at an alternative
      point in the virus replication cycle will make a valuable addition to the treatment of HIV
      infection.

      This Phase I/II open-label, dose-escalating, randomized study is divided into 2 parts.
      Patients may participate in Part A and/or Part B. Part A (single dosing): 12 patients are
      sequentially assigned to receive 1 of 3 doses of T-20 given once on Day 0 by SC injection
      into the abdomen, deltoid area, or anterior aspect of the thigh and once on Day 1 by IV
      infusion. Provided safety criteria are met, patients who complete Part A, or new enrollees
      who did not participate in Part A, enroll in Part B. Doses for Part B are determined by
      pharmacokinetic data obtained in Part A. [AS PER AMENDMENT 4/20/00: Current data has now
      projected a pediatric dose. Each child will move to chronic dosing in Part B provided the
      child has no Grade 3 or higher toxicity to study drug through Day 7 in Part A.] Part B
      (multiple dosing): Patients are randomly assigned to 1 of 3 dose cohorts to receive 24 weeks
      [AS PER AMENDMENT 12/7/00: 48 weeks] of treatment (optional extension to 48 weeks [AS PER
      AMENDMENT 12/7/00: 96 weeks]) with bid SC injections of T-20. Cohort 1 receives the dose
      identified in Part A (Dose 1) as the lowest dose that is well tolerated and that achieves the
      target trough plasma concentration. Cohort 2 receives the next higher dose from Dose 1 (Dose
      2). Cohort 3 receives either Dose 1 or Dose 2, depending on the tolerability and antiviral
      activity of each dose. [AS PER AMENDMENT 4/20/00: Cohort 1 receives 30 mg/m2 SC bid (Dose 1);
      Cohort 2 receives 60 mg/m2 SC bid (Dose 2); and Cohort 3 receives Dose 1 or 2 SC bid.] On Day
      7 of T-20 dosing, children begin a new antiretroviral therapy regimen chosen by the site
      investigator based on study parameters. (Abacavir and amprenavir are not allowed for this
      regimen.) [AS PER AMENDMENT 1/6/00: Abacavir and amprenavir are now allowed.] The first
      injection will be given in the clinic and a parent/guardian will be trained to give
      successive injections. [AS PER AMENDMENT 4/20/00: The 2 doses given prior to obtaining trough
      levels on Days 1 and 7 must be directly observed by medical personnel.] Patients undergo
      clinical and laboratory evaluations to monitor viral load, HIV-related symptoms, and
      pharmacokinetics at time points throughout the study. Patients participating in Part A are
      evaluated at the clinic on Days 0, 1, and 7. Patients participating in Part B are evaluated
      at the clinic 6 times during the first 3 weeks and then every 4 weeks through Week 24. [AS
      PER AMENDMENT 12/7/00: Patients participating in Part B are evaluated at the clinic 6 times
      during the first 3 weeks, every 4 weeks through Week 24, and then every 8 weeks through Week
      48.]
    

Intervention name(s): Enfuvirtide
Intervention type(s): Drug
Intervention MeSH terms: Enfuvirtide
Primary purpose: Treatment
Keywords: Injections, Intravenous; Injections, Subcutaneous; Drug Therapy, Combination; HIV Protease Inhibitors; Membrane Fusion; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Viral Load; peptide T20