Safety and Efficacy of Switching From Stavudine or Zidovudine to Tenofovir DF in HIV-1 Infected Children

Phase 3

Completed

• Conditions: HIV Infections
• Interventions: Drug: Tenofovir DF; Drug: Zidovudine; Drug: Stavudine

• Registration Number: NCT00528957
• Lead Sponsor: Gilead Sciences

Brief Summary

The primary objective of this study is to assess the efficacy of switching to tenofovir disoproxil fumarate (TDF) compared to continuing stavudine or zidovudine in maintaining virologic suppression in HIV-1 infected children.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-12-28
• Study First Submitted: 2007-01-03
• Study First Submitted QC: 2007-09-10
• Study First Posted: 2007-09-14
• Primary Completion: 2009-04-06
• Disposition First Submitted: 2011-06-08
• Disposition First Submitted QC: 2011-06-08
• Disposition First Posted: 2011-06-23
• Results First Submitted: 2012-02-15
• Results First Submitted QC: 2012-02-15
• Results First Posted: 2012-03-22
• Study Completion: 2017-08-16
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-14
• Last Update Posted: 2018-03-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 97

Inclusion Criteria

• Documented laboratory diagnosis of HIV-1 infection
• Plasma HIV-1 RNA < 400 copies/mL
• Currently on a stable stavudine or zidovudine -containing antiretroviral therapy regimen for at least 12 weeks
• Naive to tenofovir DF

Key Inclusion Criteria for the First 96-Week Extension

• Completed 48 weeks of treatment in Arm 1 or Arm 2 of the study
• <18 years of age (at the start of the extension)
• Participants initially randomized to Arm 2 will be given the option to replace stavudine or zidovudine with tenofovir DF in the 96-week extension at the investigator's discretion, if the investigator determines that tenofovir DF is safe and beneficial for the participant.

Key Inclusion Criteria for the Second and Third 96-Week Extension and Fourth Open-Ended Extension

• Completed of treatment with study drug in the first extension phase
• <18 years of age at the start of the extension. This inclusion criterion is not applicable in those regions where tenofovir DF is not commercially available for treatment of HIV-1 infection in adults.

Key

Exclusion Criteria

• Participants receiving ongoing therapy with any of the following
• Nephrotoxic agents
• Systemic chemotherapeutic agents
• Systemic corticosteroids
• Interleukin 2 (IL 2) and other immunomodulating agents
• Investigational agents
• Pregnant or lactating participants
• Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication
• Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance
• Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma.
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic therapy within 15 days prior to screening
• Prior history of significant renal disease (ie, nephrotic syndrome, renal dysgenesis, polycystic kidney disease, congenital nephrosis)
• Prior history of significant bone disease (ie, osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondroses, multiple bone fractures)

Note: Other protocol defined Inclusion/ Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tenofovir DF	Tenofovir DF	-
stavudine or zidovudine	Zidovudine	-
stavudine or zidovudine	Stavudine	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48	48 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 48 weeks of exposure to randomized study drug.

Secondary Outcome Measures

Name	Time	Method
Virologic Success at 48 Weeks (HIV-1 RNA Cutoff at 400 Copies/mL, Snapshot)	48 weeks	This is the percentage of participants with virologic success after 48 weeks of exposure to randomized study drug. The percentage of participants achieving HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Virologic Success at 48 Weeks (HIV-1 RNA Cutoff at 50 Copies/mL, Snapshot)	48 weeks	This is the percentage of participants with virologic success after 48 weeks of exposure to randomized study drug. The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96	96 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 96 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144	144 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 144 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 192 Weeks	192 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 192 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 240 Weeks	240 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 240 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 288 Weeks	288 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 288 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 336 Weeks	336 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 336 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 384 Weeks	384 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 384 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 432 Weeks	432 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 432 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 480 Weeks	480 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 480 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 528 Weeks	528 weeks	This is the percentage of participants with HIV-1 RNA \< 400 copies/mL after 528 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 48 Weeks	48 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 48 weeks of exposure to randomized study drug.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 96 Weeks	96 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 96 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 144 Weeks	144 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 144 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 192 Weeks	192 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 192 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 240 Weeks	240 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 240 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 288 Weeks	288 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 288 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 336 Weeks	336 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 336 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 384 Weeks	384 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 384 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 432 Weeks	432 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 432 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 480 Weeks	480 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 480 weeks of exposure to TDF.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 528 Weeks	528 weeks	This is the percentage of participants with HIV-1 RNA \< 50 copies/mL after 528 weeks of exposure to TDF.
Change From Baseline in CD4 Percentage at 48 Weeks	Baseline and 48 weeks	This is the change from baseline in CD4 percentage after 48 weeks of exposure to randomized study drug.
Change From Baseline in CD4 Percentage at 96 Weeks	Baseline and 96 weeks	This is the change from baseline in CD4 percentage after 96 weeks of exposure to TDF.
Change From Baseline in CD4 Percentage at 144 Weeks	Baseline and 144 weeks	This is the change from baseline in CD4 percentage after 144 weeks of exposure to TDF.
Change From Baseline in CD4 Percentage at 192 Weeks	Baseline and 192 weeks	This is the change from baseline in CD4 percentage after 192 weeks of exposure to TDF.
Change From Baseline in CD4 Percentage at 240 Weeks	Baseline and 240 weeks	This is the change from baseline in CD4 percentage after 240 weeks of exposure to TDF.
Change From Baseline in CD4 Percentage at 288 Weeks	Baseline and 288 weeks	This is the change from baseline in CD4 percentage after 288 weeks of exposure to TDF.
Change From Baseline in CD4 Percentage at 336 Weeks	Baseline and 336 weeks	This is the change from baseline in CD4 percentage after 336 weeks of exposure to TDF.
Change From Baseline in CD4 Percentage at 384 Weeks	Baseline and 384 weeks	This is the change from baseline in CD4 percentage after 384 weeks of exposure to TDF.
Change From Baseline in CD4 Percentage at 432 Weeks	Baseline and 432 weeks	This is the change from baseline in CD4 percentage after 432 weeks of exposure to TDF.
Change From Baseline in CD4 Percentage at 480 Weeks	Baseline and 480 weeks	This is the change from baseline in CD4 percentage after 480 weeks of exposure to TDF.
Change From Baseline in CD4 Percentage at 528 Weeks	Baseline and 528 weeks	This is the change from baseline in CD4 percentage after 528 weeks of exposure to TDF.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 48 Weeks	Baseline and 48 weeks	This is the change from baseline in CD4 cell count after 48 weeks of exposure to randomized study drug.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 96 Weeks	Baseline and 96 weeks	This is the change from baseline in CD4 cell count after 96 weeks of exposure to TDF.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 144 Weeks	Baseline and 144 weeks	This is the change from baseline in CD4 cell count after 144 weeks of exposure to TDF.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 192 Weeks	Baseline and 192 weeks	This is the change from baseline in CD4 cell count after 192 weeks of exposure to TDF.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 240 Weeks	Baseline and 240 weeks	This is the change from baseline in CD4 cell count after 240 weeks of exposure to TDF.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 288 Weeks	Baseline and 288 weeks	This is the change from baseline in CD4 cell count after 288 weeks of exposure to TDF.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 336 Weeks	Baseline and 336 weeks	This is the change from baseline in CD4 cell count after 336 weeks of exposure to TDF.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 384 Weeks	Baseline and 384 weeks	This is the change from baseline in CD4 cell count after 384 weeks of exposure to TDF.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 432 Weeks	Baseline and 432 weeks	This is the change from baseline in CD4 cell count after 432 weeks of exposure to TDF.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 480 Weeks	Baseline and 480 weeks	This is the change from baseline in CD4 cell count after 480 weeks of exposure to TDF.
Change From Baseline in CD4 Cell Count (Cells/mm^3) at 528 Weeks	Baseline and 528 weeks	This is the change from baseline in CD4 cell count after 528 weeks of exposure to TDF.

Trial Locations

Locations (9)

Hospital del Nino; 🇵🇦 Panama City, Panama

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States

Children's Diagnostic and Treatment Center, Inc; 🇺🇸 Fort Lauderdale, Florida, United States

Jeffrey Goodman Special Care Clinic; 🇺🇸 Los Angeles, California, United States

St. Christopher's Hospital for Children; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Florida, Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Imperial College London, Paediatrics Infectious Diseases; 🇬🇧 London, United Kingdom

Great Ormond Street Hospital; 🇬🇧 London, United Kingdom

University California Los Angeles, School of Medicine, Pediatric, Infectious Diseases; 🇺🇸 Los Angeles, California, United States