The Safety and Effectiveness of Zidovudine Plus Lamivudine, Used With and Without 1592U89, in HIV-1 Infected Children Who Have Taken Anti-HIV-1 Drugs

A Double-Blind, Randomized, Multicenter Trial to Evaluate the Safety and Efficacy of the Combination of 1592U89/Zidovudine (ZDV)/Lamivudine (3TC) Versus the Combination of Zidovudine (ZDV)/Lamivudine (3TC) in HIV-1 Therapy-Experienced Pediatric Patients.

To compare the safety, tolerance, durability of the viral load response and the antiviral activity of the 1592U89/zidovudine(ZDV)/lamivudine (3TC) regimen vs. ZDV/3TC regimen. To determine the clinical efficacy of the two regimens as measured survival, disease progression, weight growth velocity, and neuropsychological or neurological changes. To assess the development of viral resistance and relative pharmacokinetics associated with each regimen.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Lamivudine; Drug: Zidovudine; Drug: Abacavir sulfate

Detailed Description

Patients are randomized to receive blinded treatment with ZDV/3TC alone or in combination with 1592U89, orally for 16 weeks. If after the 16-week period certain criteria are met, patients may have the option to switch to open-label treatment for the remainder of the study period.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Univ Alabama - Birmingham / Dept of Pediatrics / UAB Station
  • California
    • Los Angeles, California, United States, 90033
      • Los Angeles County - USC Med Ctr
    • Los Angeles, California, United States, 90027
      • Children's Hosp Los Angeles
  • Florida
    • Fort Lauderdale, Florida, United States, 33301
      • Children's Diagnostic Treatment Ctr
    • Gainesville, Florida, United States, 326100296
      • Univ of Florida - Gainesville / Infectious Dis & Immun
    • Miami, Florida, United States, 33136
      • Univ of Miami / Fox Cancer Research Ctr
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hosp for Women and Children
    • Riviera Beach, Florida, United States, 33404
      • Pediatric Special Immunology Clinic / HRS / PBC PHU
    • Saint Petersburg, Florida, United States, 33701
      • Univ of South Florida All Children's Hosp
    • Tampa, Florida, United States, 33606
      • Dr Patricia Emmanuel
  • Illinois
    • Chicago, Illinois, United States, 60608
      • Mt Sinai Hosp Med Ctr / Dept of Pediatrics
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Univ Med School
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Univ of Minnesota Med School
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • UMDNJ / Division of Allergy Immunology & Infectious Diseases
  • New York
    • Bronx, New York, United States, 10457
      • Bronx Lebanon Hosp Ctr / Dept of Pediatrics
    • Buffalo, New York, United States, 14222
      • PACT Program
    • Great Neck, New York, United States, 11021
      • North Shore Univ Hosp / Pediatric Immunology
    • New Hyde Park, New York, United States, 11040
      • Schneider Children's Hosp
    • New York, New York, United States, 10021
      • New York Hosp - Cornell / Program for Children with AIDS
    • New York, New York, United States, 10025
      • St Luke's - Roosevelt Hosp Ctr
    • Stony Brook, New York, United States, 117948111
      • SUNY Health Ctr at Stony Brook / Pediatric Infectious Dis
    • Syracuse, New York, United States, 13210
      • SUNY Health Sciences Ctr at Syracuse / Dept of Pediatrics
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Univ of North Carolina / Pediatric Infectious Diseases
    • Durham, North Carolina, United States, 27710
      • Duke Univ Med Ctr / Pediatrics Dept / Infec Dis
  • Ohio
    • Dayton, Ohio, United States, 454041815
      • The Children's Med Ctr / Division of Infectious Dis
  • South Carolina
    • Charleston, South Carolina, United States, 294253312
      • Med Univ of South Carolina
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Med Ctr of Dallas / ARMS Clinic
    • Fort Worth, Texas, United States, 76104
      • Cook's Ft Worth Children Med Ctr / Pediatric Inf Dis
    • San Antonio, Texas, United States, 78284
      • Univ of Texas Health Sciences Ctr
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Eastern VA Med Sch / Children's Hosp of the King's Daughters

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• Intravenous immunoglobulin G, erythropoietin, G-CSF and GM-CSF.
• Opportunistic infection prophylaxis.

Patients must have:

• HIV-1 infection documented by:

< 18 months of age:

• one positive viral test culture and one other positive viral test (culture, PCR, p24 antigen, or Immune Complex Dissociation p24 antigen) on two different specimens.

>= 18 months of age:

• two positive viral tests as stated above, one or both of which may be determined by a federally documented ELISA and confirmed by Western blot or Indirect Fluorescent Antibody test.
• Any of the CDC Categories:
• 1, 2, 3, and N, A, B, and C of the 1994 Revised Classification System for HIV Infection in Children Less than 13 Years of Age.
• CD4+ count >= 15% within 14 days prior to study drug administration.
• No active or ongoing AIDS-defining opportunistic infection that precludes absorption of study drug or observation of a study parameter.
• Signed, informed consent from parent or legal guardian for patients under 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Serious bacterial infection that precludes absorption of study drug or observation of a study parameter.
• Documented hypersensitivity to a nucleoside analog.
• Co-enrollment in certain opportunistic infection protocols is not exclusionary if approval is obtained.
• Malignancy.
• Life-threatening infection or other chronic disease that may compromise patient safety.
• Grade 3/4 clinical or laboratory toxicity or current grade 2 or higher pancreatic amylase or lipase toxicity as defined by the ACTG Toxicity Tables within 14 days prior to study entry.

Concurrent Medication:

Excluded:

• Other anti-HIV therapy.
• Probenecid.
• Biologic response modifier (unless listed under included concurrent medication) and megestrol acetate.
• Human growth hormone.
• Immunomodulators and cytotoxic chemotherapeutic agents.
• Systemic corticosteroids > 14 days without approval.
• Investigational agents.

Concurrent Treatment:

Excluded:

Radiation therapy.

Patients with the following prior conditions are excluded:

• History of clinically relevant pancreatitis or hepatitis within the past 6 months.
• Participation in a vaccine trial.

Prior Medication:

Excluded:

• Protease inhibitor therapy within 2 weeks prior to randomization.
• Interleukins or interferons within 30 days prior to study drug administration.
• Investigational drugs within 14 days prior to randomization.
• HIV vaccine dose within past 30 days.

Required:

> 12 weeks prior antiretroviral therapy and unchanged therapy 12 weeks prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment

Collaborators and Investigators

• Sponsor: Glaxo Wellcome

Study record dates

Study Major Dates

• Study Start: December 7, 2022
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: November 1, 1998

More Information

Terms related to this study

• Keywords: Child Development; Drug Therapy, Combination; Reverse Transcriptase Inhibitors; Anti-HIV Agents; HIV-1; Lamivudine; Viral Load; Zidovudine; abacavir
• 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Lamivudine; Zidovudine; Abacavir
• Other Study ID Numbers: 238L; CNAA3006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No