Clinical trial NCT00000913: A Study to Compare Two Anti-HIV Combination Therapies Each Containing Saquinavir in HIV-Positive Children
Official title: A Randomized Trial of Two Saquinavir-Containing Combination Treatment Regimens in Children With HIV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Saquinavir
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 50
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 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.

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

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham / Childrens Hosp of AL
state: Alabama
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham - Pediatric
state: Alabama
city: Long Beach
country: United States
facility: Long Beach Memorial (Pediatric)
state: California
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Oakland
country: United States
facility: Children's Hosp of Oakland
state: California
city: San Francisco
country: United States
facility: UCSF / Moffitt Hosp - Pediatric
state: California
city: New Haven
country: United States
facility: Yale Univ Med School
state: Connecticut
city: Washington
country: United States
facility: Howard Univ Hosp
state: District of Columbia
city: Miami
country: United States
facility: Univ of Miami (Pediatric)
state: Florida
city: Riviera Beach
country: United States
facility: Palm Beach County Health Dept
state: Florida
city: Atlanta
country: United States
facility: Emory Univ Hosp / Pediatrics
state: Georgia
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Univ of Illinois College of Medicine / Pediatrics
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's Memorial Hosp
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ / Charity Hosp of New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: Univ of Maryland at Baltimore / Univ Med Ctr
state: Maryland
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: Jackson
country: United States
facility: Univ of Mississippi Med Ctr
state: Mississippi
city: Newark
country: United States
facility: Univ of Medicine & Dentistry of New Jersey / Univ Hosp
state: New Jersey
city: Albany
country: United States
facility: Children's Hosp at Albany Med Ctr
state: New York
city: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr
state: New York
city: Bronx
country: United States
facility: Bronx Municipal Hosp Ctr/Jacobi Med Ctr
state: New York
city: Great Neck
country: United States
facility: North Shore Univ Hosp
state: New York
city: New York
country: United States
facility: Cornell Univ Med College
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
state: New York
city: New York
country: United States
facility: Harlem Hosp Ctr
state: New York
city: Stony Brook
country: United States
facility: State Univ of New York at Stony Brook
state: New York
city: Philadelphia
country: United States
facility: Saint Christopher's Hosp for Children
state: Pennsylvania
city: Charleston
country: United States
facility: Med Univ of South Carolina
state: South Carolina
city: Richmond
country: United States
facility: Med College of Virginia
state: Virginia
city: Seattle
country: United States
facility: Children's Hospital & Medical Center / Seattle ACTU
state: Washington
city: Bayamon
country: Puerto Rico
facility: Ramon Ruiz Arnau Univ Hosp / Pediatrics
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico / Univ Children's Hosp AIDS
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp
Study officials:
name: Mark Kline
role: STUDY_CHAIR
name: Courtney Fletcher
role: STUDY_CHAIR
References:
citation: 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)
citation: 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]
citation: 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)
citation: 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]