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

HIV Infections Clinical Trial

Official title:

A Phase I/II Study of T-20, a Fusion Inhibitor, in HIV-1 Infected Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001118
• Other study ID #: P1005
• Secondary ID: 11642ACTG P1005P
• Status: Completed
• Phase: Phase 1
• Est. completion date: December 2002

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 2002
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 12 Years

Eligibility

Inclusion Criteria

Children may be eligible for this study if they:

• Are 3 to 12 years old (consent of parent or guardian required).

• Are HIV-positive.

• Are receiving combination anti-HIV therapy. He/she must have been taking this combination for at least 16 weeks, and it must include either 2 NRTIs alone or 2 NRTIs plus either an NNRTI or a PI. (This study has been changed. This no longer has to be a child's first anti-HIV drug combination.)

• Have a viral load greater than 10,000 copies/ml while taking this anti-HIV drug combination.

• Have never received treatment with a PI or an NNRTI. (One or two doses are allowed.)

• Have never taken at least 1 NRTI.

Exclusion Criteria

Children will not be eligible for this study if they:

• Are receiving treatment for an opportunistic (AIDS-related) or serious bacterial infection at the time of study entry.

• Are receiving chemotherapy for cancer.

• Have certain serious diseases (other than HIV) or conditions.

• Have received or are currently receiving certain medications.

• Are pregnant.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Enfuvirtide

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hosp	San Juan
United States	Boston City Hosp / Pediatrics	Boston	Massachusetts
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Children's Hosp of Michigan	Detroit	Michigan
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	North Shore Univ Hosp	Great Neck	New York
United States	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida
United States	UCSD Med Ctr / Pediatrics / Clinical Sciences	La Jolla	California
United States	Long Beach Memorial (Pediatric)	Long Beach	California
United States	Children's Hosp of Los Angeles/UCLA Med Ctr	Los Angeles	California
United States	Univ of Miami (Pediatric)	Miami	Florida
United States	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	Metropolitan Hosp Ctr	New York	New York
United States	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey
United States	UCSF / Moffitt Hosp - Pediatric	San Francisco	California
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	SUNY Health Sciences Ctr at Syracuse / Pediatrics	Syracuse	New York
United States	Children's Hosp of Washington DC	Washington	District of Columbia
United States	Howard Univ Hosp	Washington	District of Columbia
United States	Univ of Massachusetts Med School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (4)

Church JA, Cunningham C, Hughes M, Palumbo P, Mofenson LM, Delora P, Smith E, Wiznia A, Purdue L, Hawkins E, Sista P; PACTG P1005 Study Team. Pediatric AIDS Clinical Trials Group. Safety and antiretroviral activity of chronic subcutaneous administration o — View Citation

Church JA, Hughes M, Chen J, Palumbo P, Mofenson LM, Delora P, Smith E, Wiznia A, Hawkins E, Sista P, Cunningham CK; Pediatric AIDS Clinical Trials Group P1005 Study Team. Long term tolerability and safety of enfuvirtide for human immunodeficiency virus 1 — View Citation

Kosel B, Church J, Cunningham C, Sista P, Aweeka F. Pharmacokinetics (PK) of selected doses of T-20, a fusion inhibitor, in HIV-1-infected children. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 726)

Soy D, Aweeka FT, Church JA, Cunningham CK, Palumbo P, Kosel BW, Sheiner LB; Pediatric AIDS Clinical Trial Group (PACTG) Study P1005 Investigators. Population pharmacokinetics of enfuvirtide in pediatric patients with human immunodeficiency virus: searchi — View Citation

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