Clinical trial NCT00006325: Safety, Tolerability, and Anti-HIV Activity of PEG-Intron in HIV-Positive Children
Official title: Safety, Tolerability, Antiviral Activity, and Pharmacokinetics of PEG-Intron in HIV-1 Infected Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Polyethylene Glycols
Interferon Alfa-2b
HIV-1
Dose-Response Relationship, Drug
Drug Therapy, Combination
Virus Inhibitors
Anti-HIV Agents
Pharmacokinetics
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2001-08-31
Enrollment: 54
Sex: ALL
Minimum age (years): 3
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.)

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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial (Pediatric)
state: California
city: Los Angeles
country: United States
facility: Children's Hosp of Los Angeles/UCLA Med Ctr
state: California
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: San Francisco
country: United States
facility: UCSF / Moffitt Hosp - Pediatric
state: California
city: Farmington
country: United States
facility: Connecticut Children's Med Ctr
state: Connecticut
city: Jacksonville
country: United States
facility: Univ of Florida Health Science Ctr / Pediatrics
state: Florida
city: Miami
country: United States
facility: Univ of Miami (Pediatric)
state: Florida
city: Boston
country: United States
facility: Children's Hosp of Boston
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Med Ctr of Springfield
state: Massachusetts
city: Worcester
country: United States
facility: Univ of Massachusetts Med School
state: Massachusetts
city: Newark
country: United States
facility: Univ of Medicine & Dentistry of New Jersey / Univ Hosp
state: New Jersey
city: New Hyde Park
country: United States
facility: Schneider Children's Hosp
state: New York
city: New York
country: United States
facility: Harlem Hosp Ctr
state: New York
city: Syracuse
country: United States
facility: SUNY Health Sciences Ctr at Syracuse / Pediatrics
state: New York
city: Houston
country: United States
facility: Texas Children's Hosp / Baylor Univ
state: Texas
Study officials:
name: Katherine Luzuriaga
role: STUDY_CHAIR
name: Andrea Kovacs
role: STUDY_CHAIR
References: