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

NCT ID: NCT00001118

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2002-12-31

Brief Summary

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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

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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. \[AS PER AMENDMENT 12/7/00: Patients participating in Part B are evaluated at the clinic 6 times during the first 3 weeks, every 4 weeks through Week 24, and then every 8 weeks through Week 48.\]

Conditions

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HIV Infections

Keywords

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Injections, Intravenous Injections, Subcutaneous Drug Therapy, Combination HIV Protease Inhibitors Membrane Fusion Reverse Transcriptase Inhibitors Anti-HIV Agents Viral Load peptide T20

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Enfuvirtide

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

3 Years

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joseph Church

Role: STUDY_CHAIR

Coleen Cunningham

Role: STUDY_CHAIR

Locations

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UCSD Med Ctr / Pediatrics / Clinical Sciences

La Jolla, California, United States

Site Status

Long Beach Memorial (Pediatric)

Long Beach, California, United States

Site Status

Children's Hosp of Los Angeles/UCLA Med Ctr

Los Angeles, California, United States

Site Status

UCSF / Moffitt Hosp - Pediatric

San Francisco, California, United States

Site Status

Children's Hosp of Washington DC

Washington D.C., District of Columbia, United States

Site Status

Howard Univ Hosp

Washington D.C., District of Columbia, United States

Site Status

Univ of Florida Health Science Ctr / Pediatrics

Jacksonville, Florida, United States

Site Status

Univ of Miami (Pediatric)

Miami, Florida, United States

Site Status

Tulane Univ / Charity Hosp of New Orleans

New Orleans, Louisiana, United States

Site Status

Children's Hosp of Boston

Boston, Massachusetts, United States

Site Status

Boston City Hosp / Pediatrics

Boston, Massachusetts, United States

Site Status

Baystate Med Ctr of Springfield

Springfield, Massachusetts, United States

Site Status

Univ of Massachusetts Med School

Worcester, Massachusetts, United States

Site Status

Children's Hosp of Michigan

Detroit, Michigan, United States

Site Status

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, United States

Site Status

North Shore Univ Hosp

Great Neck, New York, United States

Site Status

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Site Status

Metropolitan Hosp Ctr

New York, New York, United States

Site Status

Harlem Hosp Ctr

New York, New York, United States

Site Status

SUNY Health Sciences Ctr at Syracuse / Pediatrics

Syracuse, New York, United States

Site Status

Bronx Lebanon Hosp Ctr

The Bronx, New York, United States

Site Status

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

The Bronx, New York, United States

Site Status

Duke Univ Med Ctr

Durham, North Carolina, United States

Site Status

Med Univ of South Carolina

Charleston, South Carolina, United States

Site Status

San Juan City Hosp

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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)

Reference Type BACKGROUND

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 of T-20 in human immunodeficiency virus 1-infected children. Pediatr Infect Dis J. 2002 Jul;21(7):653-9. doi: 10.1097/00006454-200207000-00010.

Reference Type RESULT
PMID: 12237598 (View on PubMed)

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: searching for exposure-response relationships. Clin Pharmacol Ther. 2003 Dec;74(6):569-80. doi: 10.1016/j.clpt.2003.09.002.

Reference Type RESULT
PMID: 14663459 (View on PubMed)

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-infected children. Pediatr Infect Dis J. 2004 Aug;23(8):713-8. doi: 10.1097/01.inf.0000133045.45316.6a.

Reference Type RESULT
PMID: 15295220 (View on PubMed)

Other Identifiers

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11642

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG P1005

Identifier Type: -

Identifier Source: secondary_id

PACTG P1005

Identifier Type: -

Identifier Source: secondary_id

T20-204

Identifier Type: -

Identifier Source: secondary_id

P1005

Identifier Type: -

Identifier Source: org_study_id