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Study of a New Anti-HIV Drug, T-20, in HIV-Infected Children

Phase 1
Completed
Conditions
HIV Infections
Registration Number
NCT00001118
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief 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. \[AS PER AMENDMENT 12/7/00: Patients participating in Part B are evaluated at the clinic 6 times during the first 3 weeks, every 4 weeks through Week 24, and then every 8 weeks through Week 48.\]

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (25)

Long Beach Memorial (Pediatric)

🇺🇸

Long Beach, California, United States

Univ of Florida Health Science Ctr / Pediatrics

🇺🇸

Jacksonville, Florida, United States

Harlem Hosp Ctr

🇺🇸

New York, New York, United States

Med Univ of South Carolina

🇺🇸

Charleston, South Carolina, United States

Children's Hosp of Los Angeles/UCLA Med Ctr

🇺🇸

Los Angeles, California, United States

North Shore Univ Hosp

🇺🇸

Great Neck, New York, United States

Duke Univ Med Ctr

🇺🇸

Durham, North Carolina, United States

Children's Hosp of Michigan

🇺🇸

Detroit, Michigan, United States

Bronx Lebanon Hosp Ctr

🇺🇸

Bronx, New York, United States

SUNY Health Sciences Ctr at Syracuse / Pediatrics

🇺🇸

Syracuse, New York, United States

Bellevue Hosp / New York Univ Med Ctr

🇺🇸

New York, New York, United States

Metropolitan Hosp Ctr

🇺🇸

New York, New York, United States

UCSF / Moffitt Hosp - Pediatric

🇺🇸

San Francisco, California, United States

Children's Hosp of Washington DC

🇺🇸

Washington, District of Columbia, United States

Univ of Miami (Pediatric)

🇺🇸

Miami, Florida, United States

Children's Hosp of Boston

🇺🇸

Boston, Massachusetts, United States

Boston City Hosp / Pediatrics

🇺🇸

Boston, Massachusetts, United States

Baystate Med Ctr of Springfield

🇺🇸

Springfield, Massachusetts, United States

Univ of Massachusetts Med School

🇺🇸

Worcester, Massachusetts, United States

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

🇺🇸

Bronx, New York, United States

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

🇺🇸

Newark, New Jersey, United States

San Juan City Hosp

🇵🇷

San Juan, Puerto Rico

UCSD Med Ctr / Pediatrics / Clinical Sciences

🇺🇸

La Jolla, California, United States

Tulane Univ / Charity Hosp of New Orleans

🇺🇸

New Orleans, Louisiana, United States

Howard Univ Hosp

🇺🇸

Washington, District of Columbia, United States

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