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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Tenofovir DF
* Drug: Zidovudine
* Drug: Stavudine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenofovir DF<br> | Drug: Tenofovir DF<br>* Tenofovir DF (oral powder or tablet): 300-mg tablets for participants > 37 kg; 8-mg/kg oral powder (up to 300 mg) for participants ≤ 37 kg. During the extension phase, participants whose weight increases to > 37 kg may be switched from the oral powder to the tenofovir DF tablet.<br>* Other names: Viread®;|
| Active Comparator: stavudine or zidovudine<br> | Drug: Zidovudine<br>* Zidovudine as prescribed by the investigator prior to study entry (pediatric participants < 30 kg: 1 mg/kg/dose given every 12 hours; pediatric participants ≥ 30 kg: 30 mg twice daily).<br>Drug: Stavudine<br>* Stavudine as prescribed by the investigator prior to study entry (pediatric participants 6 weeks to 12 years of age: 160 mg/m^2 every 8 hours; pediatric participants > 12 years of age: 300 mg twice daily).<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic Success at 48 Weeks (HIV-1 RNA Cutoff at 400 Copies/mL, Snapshot) | 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. | 48 weeks | 
| Virologic Success at 48 Weeks (HIV-1 RNA Cutoff at 50 Copies/mL, Snapshot) | 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. | 48 weeks | 
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 | This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 96 weeks of exposure to TDF. | 96 weeks | 
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144 | This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 144 weeks of exposure to TDF. | 144 weeks | 
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 192 Weeks | This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 192 weeks of exposure to TDF. | 192 weeks | 
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 240 Weeks | This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 240 weeks of exposure to TDF. | 240 weeks | 
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 288 Weeks | This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 288 weeks of exposure to TDF. | 288 weeks | 
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 336 Weeks | This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 336 weeks of exposure to TDF. | 336 weeks | 
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 384 Weeks | This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 384 weeks of exposure to TDF. | 384 weeks | 
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 432 Weeks | This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 432 weeks of exposure to TDF. | 432 weeks | 
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 480 Weeks | This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 480 weeks of exposure to TDF. | 480 weeks | 
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 528 Weeks | This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 528 weeks of exposure to TDF. | 528 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 48 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 48 weeks of exposure to randomized study drug. | 48 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 96 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 96 weeks of exposure to TDF. | 96 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 144 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 144 weeks of exposure to TDF. | 144 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 192 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 192 weeks of exposure to TDF. | 192 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 240 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 240 weeks of exposure to TDF. | 240 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 288 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 288 weeks of exposure to TDF. | 288 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 336 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 336 weeks of exposure to TDF. | 336 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 384 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 384 weeks of exposure to TDF. | 384 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 432 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 432 weeks of exposure to TDF. | 432 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 480 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 480 weeks of exposure to TDF. | 480 weeks | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 528 Weeks | This is the percentage of participants with HIV-1 RNA < 50 copies/mL after 528 weeks of exposure to TDF. | 528 weeks | 
| Change From Baseline in CD4 Percentage at 48 Weeks | This is the change from baseline in CD4 percentage after 48 weeks of exposure to randomized study drug. | Baseline and 48 weeks | 
| Change From Baseline in CD4 Percentage at 96 Weeks | This is the change from baseline in CD4 percentage after 96 weeks of exposure to TDF. | Baseline and 96 weeks | 
| Change From Baseline in CD4 Percentage at 144 Weeks | This is the change from baseline in CD4 percentage after 144 weeks of exposure to TDF. | Baseline and 144 weeks | 
| Change From Baseline in CD4 Percentage at 192 Weeks | This is the change from baseline in CD4 percentage after 192 weeks of exposure to TDF. | Baseline and 192 weeks | 
| Change From Baseline in CD4 Percentage at 240 Weeks | This is the change from baseline in CD4 percentage after 240 weeks of exposure to TDF. | Baseline and 240 weeks | 
| Change From Baseline in CD4 Percentage at 288 Weeks | This is the change from baseline in CD4 percentage after 288 weeks of exposure to TDF. | Baseline and 288 weeks | 
| Change From Baseline in CD4 Percentage at 336 Weeks | This is the change from baseline in CD4 percentage after 336 weeks of exposure to TDF. | Baseline and 336 weeks | 
| Change From Baseline in CD4 Percentage at 384 Weeks | This is the change from baseline in CD4 percentage after 384 weeks of exposure to TDF. | Baseline and 384 weeks | 
| Change From Baseline in CD4 Percentage at 432 Weeks | This is the change from baseline in CD4 percentage after 432 weeks of exposure to TDF. | Baseline and 432 weeks | 
| Change From Baseline in CD4 Percentage at 480 Weeks | This is the change from baseline in CD4 percentage after 480 weeks of exposure to TDF. | Baseline and 480 weeks | 
| Change From Baseline in CD4 Percentage at 528 Weeks | This is the change from baseline in CD4 percentage after 528 weeks of exposure to TDF. | Baseline and 528 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 48 Weeks | This is the change from baseline in CD4 cell count after 48 weeks of exposure to randomized study drug. | Baseline and 48 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 96 Weeks | This is the change from baseline in CD4 cell count after 96 weeks of exposure to TDF. | Baseline and 96 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 144 Weeks | This is the change from baseline in CD4 cell count after 144 weeks of exposure to TDF. | Baseline and 144 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 192 Weeks | This is the change from baseline in CD4 cell count after 192 weeks of exposure to TDF. | Baseline and 192 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 240 Weeks | This is the change from baseline in CD4 cell count after 240 weeks of exposure to TDF. | Baseline and 240 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 288 Weeks | This is the change from baseline in CD4 cell count after 288 weeks of exposure to TDF. | Baseline and 288 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 336 Weeks | This is the change from baseline in CD4 cell count after 336 weeks of exposure to TDF. | Baseline and 336 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 384 Weeks | This is the change from baseline in CD4 cell count after 384 weeks of exposure to TDF. | Baseline and 384 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 432 Weeks | This is the change from baseline in CD4 cell count after 432 weeks of exposure to TDF. | Baseline and 432 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 480 Weeks | This is the change from baseline in CD4 cell count after 480 weeks of exposure to TDF. | Baseline and 480 weeks | 
| Change From Baseline in CD4 Cell Count (Cells/mm^3) at 528 Weeks | This is the change from baseline in CD4 cell count after 528 weeks of exposure to TDF. | Baseline and 528 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 3, Randomized, Open-Label, Treatment-Experienced, Highly Active Antiretroviral Therapy, HIV, Tenofovir DF, Pediatrics