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

• ClinicalTrials.gov Identifier: NCT00528957
• Recruitment Status: Completed
• First Posted: September 14, 2007
• Results First Posted: March 22, 2012
• Last Update Posted: March 14, 2018
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: January 3, 2007
• First Posted Date: September 14, 2007
• Results First Submitted Date: February 15, 2012
• Results First Posted Date: March 22, 2012
• Last Update Posted Date: March 14, 2018
• Actual Study Start Date: December 28, 2006
• Actual Primary Completion Date: April 6, 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 15, 2012)

Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 [ Time Frame: 48 weeks ]

This is the percentage of participants with HIV-1 RNA < 400 copies/mL after 48 weeks of exposure to randomized study drug.

• Original Primary Outcome Measures (submitted: September 10, 2007): Primary: Proportion of patients maintaining HIV-1 RNA levels < 400 copies/mL at Week 48 in each arm

Current Secondary Outcome Measures (submitted: February 14, 2018)

• Virologic Success at 48 Weeks (HIV-1 RNA Cutoff at 400 Copies/mL, Snapshot) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline and 528 weeks ]
  This is the change from baseline in CD4 cell count after 528 weeks of exposure to TDF.

• Original Secondary Outcome Measures (submitted: September 10, 2007): Evaluate the safety and tolerability of tenofovir DF in HIV-1 infected children
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Infections

Intervention

• Drug: Tenofovir DF
  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.
  Other Name: Viread®
• Drug: Zidovudine
  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).
• Drug: Stavudine
  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).

Study Arms

• Experimental: Tenofovir DF
  Intervention: Drug: Tenofovir DF
• Active Comparator: stavudine or zidovudine
  Interventions:

  • Drug: Zidovudine
  • Drug: Stavudine

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 15, 2012): 97
• Original Estimated Enrollment (submitted: September 10, 2007): 100
• Actual Study Completion Date: August 16, 2017
• Actual Primary Completion Date: April 6, 2009 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 15 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Panama, United Kingdom, United States
• Removed Location Countries: Puerto Rico

Administrative Information

• NCT Number: NCT00528957
• Other Study ID Numbers: GS-US-104-0352; 2007-003418-32 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Not Provided
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: February 2018