Safety, Tolerability, and Anti-HIV Activity of PEG-Intron in HIV-Positive Children

Safety, Tolerability, Antiviral Activity, and Pharmacokinetics of PEG-Intron in HIV-1 Infected Children

The purpose of this study is to see if PEG-Intron is safe and tolerated when given to children, to see how much gets into the blood and how long it stays in the blood, and to see how well it works to reduce viral load (level of HIV in the blood).

PEG-Intron is an experimental drug that works differently than other anti-HIV medications. It decreases the ability of HIV to infect the T cells (a special type of cell that helps fight infection). PEG-Intron has been approved by the Food and Drug Administration (FDA) to treat hepatitis C in adults, but in this study, it is being used as an investigational agent for the treatment of HIV/AIDS. It has not been tested in children before and experience with PEG-Intron in adults is limited. (This protocol has been changed to reflect FDA approval of PEG-Intron for treating hepatitic C in adults.)

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Peginterferon alfa-2b

Detailed Description

The current optimal clinical management of HIV infection involves therapy with combinations of nucleoside and nonnucleoside reverse transcriptase inhibitors and HIV protease inhibitors. These regimens, though effective, do not completely eliminate HIV and the development of drug resistance is a major clinical problem. Interferons have been proposed as a possible treatment of HIV. Interferon-alfa inhibits HIV replication in vitro, and HIV-infected patients appear to have reduced production of interferons. Previous short-term clinical studies in adults showed anti-HIV activity, although there were safety and tolerability problems associated with the higher dose regimens used. This study will utilize a rising multiple-dose design to assess the safety, tolerability, and pharmacokinetics of single and multiple doses of PEG-Intron in HIV-infected children.

In a dose-escalation study, patients add weekly PEG-Intron to their antiretroviral therapy for up to 6 weeks. The first 2 doses are received in the clinic where parents/guardians are trained to administer injections, and succeeding doses are given at home.

Patients are enrolled from 2 cohorts. An older cohort of ages 2 to 16 years receives PEG-Intron at the lowest drug level. If the dose is tolerated, patients are added and if safety criteria are met, patients are enrolled in the next higher dose level. The dose level will be increased similarly for up to 4 doses. An optimal dose level is chosen.

Cohort II patients are a younger group ranging from 3 months to under 2 years of age. Patients initially receive the next lower PEG-Intron dose to the optimal dose identified in Cohort I [AS PER AMENDMENT 07/23/01: or 1 microg/kg if the optimal dose proves to be 1 microg/kg]. If this dose is safely tolerated, additional patients are added. If this dose level meets safety criteria, patients are enrolled to receive the optimal dose level. Patients are evaluated with the same safety criteria as Cohort I. Patients in both cohorts who have at least a 0.5 log reduction in HIV RNA at 28 days of treatment are offered continued treatment for a total of 60 weeks.

• Study Type: Interventional
• Enrollment: 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90801
      • Long Beach Memorial (Pediatric)
    • Los Angeles, California, United States, 900276016
      • Children's Hosp of Los Angeles/UCLA Med Ctr
    • Los Angeles, California, United States, 90033
      • Los Angeles County - USC Med Ctr
    • San Francisco, California, United States, 941430105
      • UCSF / Moffitt Hosp - Pediatric
  • Connecticut
    • Farmington, Connecticut, United States, 060303805
      • Connecticut Children's Med Ctr
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Univ of Florida Health Science Ctr / Pediatrics
    • Miami, Florida, United States, 33161
      • Univ of Miami (Pediatric)
  • Massachusetts
    • Boston, Massachusetts, United States, 021155724
      • Children's Hosp of Boston
    • Springfield, Massachusetts, United States, 01199
      • Baystate Med Ctr of Springfield
    • Worcester, Massachusetts, United States, 016550001
      • Univ of Massachusetts Med School
  • New Jersey
    • Newark, New Jersey, United States, 071032714
      • Univ of Medicine & Dentistry of New Jersey / Univ Hosp
  • New York
    • New Hyde Park, New York, United States, 11040
      • Schneider Children's Hosp
    • New York, New York, United States, 10037
      • Harlem Hosp Ctr
    • Syracuse, New York, United States, 13210
      • SUNY Health Sciences Ctr at Syracuse / Pediatrics
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hosp / Baylor Univ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients may be eligible for this study if they:

• Are HIV-infected infants and children aged 3 months to 16 years.
• Have been on stable anti-HIV drugs for at least 16 weeks if over 6 months of age. Infants aged 3 to 6 months must be on stable anti-HIV drugs for at least 6 weeks. Children should be receiving at least 3 anti-HIV drugs.
• Have a viral load of more than 5,000 copies/ml.
• Have written informed consent from parent or guardian and, if able, can give written consent themselves.
• Are able to follow the schedule in the protocol.
• Have a parent/guardian who is willing to comply with study requirements.
• (This study has been changed to allow any combination of 3 anti-HIV drugs and to remove CD4 requirements.)

Exclusion Criteria

Patients will not be eligible for this study if they:

• Are breast-feeding or pregnant or not using birth control, if a female.
• Have abnormal thyroid activity.
• Have severe HIV symptoms.
• Have opportunistic (AIDS-related) infections or history of such infections within the preceding 2 months.
• Have participated in a clinical trial of an experimental drug in the previous month.
• Have a positive test result for hepatitis B or C.
• Have an allergy to E. coli.
• Have a mental disorder.
• Have a history of drug dependence and measure positive when screened.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Chair: Andrea Kovacs; Study Chair: Katherine Luzuriaga

Study record dates

Study Major Dates

• Study Completion (Actual): March 1, 2004

Study Registration Dates

• First Submitted: October 2, 2000
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Anti-HIV Agents; HIV-1; Pharmacokinetics; Dose-Response Relationship, Drug; Polyethylene Glycols; Interferon Alfa-2b; Virus Inhibitors
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2b
• Other Study ID Numbers: P1017; 11652 (Registry Identifier: DAIDS ES Registry Number); PACTG P1017; ACTG P1017