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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: Tenofovir DF; Drug: Zidovudine; Drug: Stavudine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 28, 2006
• Actual Primary Completion Date: April 6, 2009
• Actual Study Completion Date: August 16, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tenofovir DF	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®
Active Comparator: stavudine or zidovudine	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).

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. 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.
40. 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.
41. 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.
42. 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.
43. 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.
44. 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.
45. 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.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 15 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Jeffrey Goodman Special Care Clinic

Los Angeles, California, United States, 90027

University California Los Angeles, School of Medicine, Pediatric, Infectious Diseases

Los Angeles, California, United States, 90095

United States, Florida

Children's Diagnostic and Treatment Center, Inc

Fort Lauderdale, Florida, United States, 33316

University of Florida, Jacksonville

Jacksonville, Florida, United States, 32209

United States, Pennsylvania

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States, 19134

United States, Tennessee

St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

Panama

Hospital del Nino

Panama City, Panama

United Kingdom

Great Ormond Street Hospital

London, United Kingdom

Imperial College London, Paediatrics Infectious Diseases

London, United Kingdom

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT00528957
• Other Study ID Numbers: GS-US-104-0352; 2007-003418-32 ( EudraCT Number )
• First Posted: September 14, 2007
• Results First Posted: March 22, 2012
• Last Update Posted: March 14, 2018
• Last Verified: February 2018

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

Keywords provided by Gilead Sciences:

Phase 3; Randomized, Open-Label; Treatment-Experienced; Highly Active Antiretroviral Therapy; HIV; Tenofovir DF; Pediatrics

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Tenofovir; Zidovudine; Stavudine; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites