A Study to Compare Two Anti-HIV Combination Therapies Each Containing Saquinavir in HIV-Positive Children

A Randomized Trial of Two Saquinavir-Containing Combination Treatment Regimens in Children With HIV Infection

The purpose of this study is to determine the safety and effectiveness of a soft-gel capsule formulation of saquinavir (SQV-SGC), a protease inhibitor, when given in combination with other anti-HIV drugs.

SQV-SGC has been tested in adults for the treatment of HIV infection, but more information is still needed about SQV-SGC in children. Recent studies suggest that this soft-gel capsule form may be safer and more effective than other protease inhibitors.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Ritonavir; Drug: Nelfinavir mesylate; Drug: Saquinavir

Detailed Description

Clinical trials in adults and children suggest that SQV-SGC has advantages over other protease inhibitors in terms of tolerability, safety, and effectiveness in patients who have failed therapy with other protease inhibitors. [AS PER AMENDMENT 11/24/99: Pharmacokinetic data from this study demonstrate lower than expected plasma SQV exposures, particularly in Arm 1. Based on these data, patients in the study will be offered the opportunity to adjust their doses. Ritonavir added to the Arm 1 regimen is expected to significantly increase SQV-SGC plasma levels and allow twice-daily dosing for SQV-SGC.]

Patients are randomized to one of two study arms. Patients in Arm 1 receive SQV-SGC plus two [AS PER AMENDMENT 11/24/99: one or two] NRTIs of choice. Patients in Arm 2 receive SQV-SGC plus NFV plus one or two NRTIs of choice. All participants are evaluated by physical examinations and laboratory tests during the study and are followed for incidence of death, cancer, or fetal abnormality. NRTIs are not provided as part of this study. [AS PER AMENDMENT 11/24/99: This study is closed to accrual. All subjects on follow-up (Cohort 1) are given the option of either discontinuing participation in ACTG 397 or participating in the next phase of the study (version 2.0). Those electing to continue participation constitute Cohort 1A. The adjusted Arm 1 regimen consists of SQV-SGC plus ritonavir plus one or two NRTIs. Ritonavir is not provided as part of this study. The Arm 2 regimen study drugs have not changed but the maximum allowable dose of SQV-SGC has increased from 1,200 mg twice-daily to 1,600 mg twice-daily. Participants continue to be followed with physical examinations and laboratory evaluations that include an intensive pharmacokinetics study on Day 14 of the new regimen.]

• Study Type: Interventional
• Enrollment: 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Bayamon, Puerto Rico, 00956
    • Ramon Ruiz Arnau Univ Hosp / Pediatrics
  • San Juan, Puerto Rico, 009367344
    • San Juan City Hosp
  • San Juan, Puerto Rico, 009365067
    • Univ of Puerto Rico / Univ Children's Hosp AIDS
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Univ of Alabama at Birmingham - Pediatric
    • Birmingham, Alabama, United States, 352330011
      • Univ of Alabama at Birmingham / Childrens Hosp of AL
  • California
    • Long Beach, California, United States, 90801
      • Long Beach Memorial (Pediatric)
    • Los Angeles, California, United States, 90033
      • Los Angeles County - USC Med Ctr
    • Oakland, California, United States, 946091809
      • Children's Hosp of Oakland
    • San Francisco, California, United States, 941430105
      • UCSF / Moffitt Hosp - Pediatric
  • Connecticut
    • New Haven, Connecticut, United States, 06504
      • Yale Univ Med School
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard Univ Hosp
  • Florida
    • Miami, Florida, United States, 33161
      • Univ of Miami (Pediatric)
    • Riviera Beach, Florida, United States, 33404
      • Palm Beach County Health Dept
  • Georgia
    • Atlanta, Georgia, United States, 30306
      • Emory Univ Hosp / Pediatrics
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp
    • Chicago, Illinois, United States, 606143394
      • Chicago Children's Memorial Hosp
    • Chicago, Illinois, United States, 60612
      • Univ of Illinois College of Medicine / Pediatrics
  • Louisiana
    • New Orleans, Louisiana, United States, 701122699
      • Tulane Univ / Charity Hosp of New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Univ of Maryland at Baltimore / Univ Med Ctr
  • Massachusetts
    • Boston, Massachusetts, United States, 021155724
      • Children's Hosp of Boston
    • Springfield, Massachusetts, United States, 01199
      • Baystate Med Ctr of Springfield
  • Mississippi
    • Jackson, Mississippi, United States, 39213
      • Univ of Mississippi Med Ctr
  • New Jersey
    • Newark, New Jersey, United States, 071032714
      • Univ of Medicine & Dentistry of New Jersey / Univ Hosp
  • New York
    • Albany, New York, United States, 12208
      • Children's Hosp at Albany Med Ctr
    • Bronx, New York, United States, 10461
      • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
    • Bronx, New York, United States, 10457
      • Bronx Lebanon Hosp Ctr
    • Great Neck, New York, United States, 11021
      • North Shore Univ Hosp
    • New York, New York, United States, 10021
      • Cornell Univ Med College
    • New York, New York, United States, 10032
      • Columbia Presbyterian Med Ctr
    • New York, New York, United States, 10032
      • Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
    • New York, New York, United States, 10037
      • Harlem Hosp Ctr
    • Stony Brook, New York, United States, 117948111
      • State Univ of New York at Stony Brook
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 191341095
      • Saint Christopher's Hosp for Children
  • South Carolina
    • Charleston, South Carolina, United States, 294253312
      • Med Univ of South Carolina
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Med College of Virginia
  • Washington
    • Seattle, Washington, United States, 981050371
      • Children's Hospital & Medical Center / Seattle ACTU

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

Your child may be eligible for this study if he or she:

• Is HIV-positive.
• Is 3 to 16 years of age (consent of parent or guardian is required).
• Has an HIV level greater than 10,000 copies/ml.
• Has never taken at least one of the following anti-HIV drugs: lamivudine, zidovudine, stavudine, or didanosine.
• Is able to swallow capsules and tablets.

Exclusion Criteria

Your child will not be eligible if he or she:

• Has cancer requiring chemotherapy.
• Has an acute opportunistic (AIDS-related) infection requiring therapy.
• Has had two or more episodes of moderate or severe diarrhea or vomiting in the 3 months prior to study entry.
• Has ever taken SQV or NFV.
• Is pregnant or breast-feeding.
• Is taking certain medications, including those that would interfere with the study drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Courtney Fletcher; Study Chair: Mark Kline

Publications and helpful links

General Publications

• Brundage RC, Kline MW, Lindsey J, Fenton T, Fletcher CV. Pharmacokinetics of saquinavir (SQV) with nelfinavir (NFV) or ritonavir (RTV) in HIV-infected children. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 728)
• Kline MW, Fletcher CV, Lindsey JC, Fenton T. A randomized trial of two saquinavir (SQV-SGC)-containing combination treatment regimens in HIV-infected children. 7th Conference on Retroviruses and Opportunistic Infections. 2000 Jan 30-Feb 2 [Poster 694]
• Kline MW, Fletcher CV, Lindsey JC, Fenton T. A randomized trial of combination therapy with saquinavir soft gelatin capsules (SQV) in HIV-infected children. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 683)
• Brundage RC, Kline MW, Lindsey JC, Fenton T, Fletcher CV. Pharmacokinetics (PK) of saquinavir (SQV) and nelfinavir (NFV) in a twice-daily (BID) regimen in HIV-infected children. 7th Conference on Retroviruses and Opportunistic Infections. 2000 Jan 30-Feb 2 [Poster 718]

Study record dates

Study Major Dates

• Study Completion (Actual): April 1, 2001

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 (Actual): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Reverse Transcriptase Inhibitors; Anti-HIV Agents; Viral Load; Saquinavir
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Nelfinavir; Saquinavir
• Other Study ID Numbers: ACTG 397; 11353 (Registry Identifier: DAIDS ES)