Clinical trial NCT00528957: Safety and Efficacy of Switching From Stavudine or Zidovudine to Tenofovir DF in HIV-1 Infected Children
Official title: A Phase III, Randomized, Open-Label Study Comparing the Safety and Efficacy of Switching Stavudine or Zidovudine to Tenofovir Disoproxil Fumarate Versus Continuing Stavudine or Zidovudine in Virologically Suppressed HIV-Infected Children Taking Highly Active Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: Phase 3
Randomized, Open-Label
Treatment-Experienced
Highly Active Antiretroviral Therapy
HIV
Tenofovir DF
Pediatrics
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2007-09-14
Enrollment: 97
Sex: ALL
Minimum age (years): 2
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Major 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.

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48
timeFrame: 48 weeks
Secondary outcomes:
measure: Virologic Success at 48 Weeks (HIV-1 RNA Cutoff at 400 Copies/mL, Snapshot)
timeFrame: 48 weeks
measure: Virologic Success at 48 Weeks (HIV-1 RNA Cutoff at 50 Copies/mL, Snapshot)
timeFrame: 48 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96
timeFrame: 96 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144
timeFrame: 144 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 192 Weeks
timeFrame: 192 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 240 Weeks
timeFrame: 240 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 288 Weeks
timeFrame: 288 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 336 Weeks
timeFrame: 336 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 384 Weeks
timeFrame: 384 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 432 Weeks
timeFrame: 432 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 480 Weeks
timeFrame: 480 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 528 Weeks
timeFrame: 528 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 48 Weeks
timeFrame: 48 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 96 Weeks
timeFrame: 96 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 144 Weeks
timeFrame: 144 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 192 Weeks
timeFrame: 192 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 240 Weeks
timeFrame: 240 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 288 Weeks
timeFrame: 288 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 336 Weeks
timeFrame: 336 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 384 Weeks
timeFrame: 384 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 432 Weeks
timeFrame: 432 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 480 Weeks
timeFrame: 480 weeks
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 528 Weeks
timeFrame: 528 weeks
measure: Change From Baseline in CD4 Percentage at 48 Weeks
timeFrame: Baseline and 48 weeks
measure: Change From Baseline in CD4 Percentage at 96 Weeks
timeFrame: Baseline and 96 weeks
measure: Change From Baseline in CD4 Percentage at 144 Weeks
timeFrame: Baseline and 144 weeks
measure: Change From Baseline in CD4 Percentage at 192 Weeks
timeFrame: Baseline and 192 weeks
measure: Change From Baseline in CD4 Percentage at 240 Weeks
timeFrame: Baseline and 240 weeks
measure: Change From Baseline in CD4 Percentage at 288 Weeks
timeFrame: Baseline and 288 weeks
measure: Change From Baseline in CD4 Percentage at 336 Weeks
timeFrame: Baseline and 336 weeks
measure: Change From Baseline in CD4 Percentage at 384 Weeks
timeFrame: Baseline and 384 weeks
measure: Change From Baseline in CD4 Percentage at 432 Weeks
timeFrame: Baseline and 432 weeks
measure: Change From Baseline in CD4 Percentage at 480 Weeks
timeFrame: Baseline and 480 weeks
measure: Change From Baseline in CD4 Percentage at 528 Weeks
timeFrame: Baseline and 528 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 48 Weeks
timeFrame: Baseline and 48 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 96 Weeks
timeFrame: Baseline and 96 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 144 Weeks
timeFrame: Baseline and 144 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 192 Weeks
timeFrame: Baseline and 192 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 240 Weeks
timeFrame: Baseline and 240 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 288 Weeks
timeFrame: Baseline and 288 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 336 Weeks
timeFrame: Baseline and 336 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 384 Weeks
timeFrame: Baseline and 384 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 432 Weeks
timeFrame: Baseline and 432 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 480 Weeks
timeFrame: Baseline and 480 weeks
measure: Change From Baseline in CD4 Cell Count (Cells/mm^3) at 528 Weeks
timeFrame: Baseline and 528 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jeffrey Goodman Special Care Clinic
state: California
city: Los Angeles
country: United States
facility: University California Los Angeles, School of Medicine, Pediatric, Infectious Diseases
state: California
city: Fort Lauderdale
country: United States
facility: Children's Diagnostic and Treatment Center, Inc
state: Florida
city: Jacksonville
country: United States
facility: University of Florida, Jacksonville
state: Florida
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Panama City
country: Panama
facility: Hospital del Nino
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: London
country: United Kingdom
facility: Imperial College London, Paediatrics Infectious Diseases
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Saez-Llorens X, Castano E, Rathore M, Church J, Deville J, Gaur A, Estripeaut D, White K, Arterburn S, Enejosa JV, Cheng AK, Chuck SL, Rhee MS. A randomized, open-label study of the safety and efficacy of switching stavudine or zidovudine to tenofovir disoproxil fumarate in HIV-1-infected children with virologic suppression. Pediatr Infect Dis J. 2015 Apr;34(4):376-82. doi: 10.1097/INF.0000000000000289.