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

NCT00528957 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-104-03522007-003418-32
• Study Type: interventional
• Target: 97
• Locations: 3 countries
• Sites: 9

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.

Conditions

HIV Infections

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (45)

• Virologic Success at 48 Weeks (HIV-1 RNA Cutoff at 400 Copies/mL, Snapshot)

  48 weeks

• Virologic Success at 48 Weeks (HIV-1 RNA Cutoff at 50 Copies/mL, Snapshot)

  48 weeks

• Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96

  96 weeks

• Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144

  144 weeks

• Percentage of Participants With HIV-1 RNA < 400 Copies/mL at 192 Weeks

  192 weeks

Study Arms (2)

Tenofovir DF

EXPERIMENTAL

Drug: Tenofovir DF

stavudine or zidovudine

ACTIVE COMPARATOR

Drug: Zidovudine; Drug: Stavudine

Interventions

Tenofovir DF DRUG

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.

Also known as: Viread®

Tenofovir DF

Zidovudine DRUG

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).

stavudine or zidovudine

Stavudine DRUG

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).

stavudine or zidovudine

Eligibility Criteria

• Age: 2 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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.
• Completed of treatment with study drug in the first extension phase

You may not qualify if:

• 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)

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (9)

Jeffrey Goodman Special Care Clinic

Los Angeles, California, 90027, United States

Location

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

Los Angeles, California, 90095, United States

Location

Children's Diagnostic and Treatment Center, Inc

Fort Lauderdale, Florida, 33316, United States

Location

University of Florida, Jacksonville

Jacksonville, Florida, 32209, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Hospital del Nino

Panama City, Panama

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Imperial College London, Paediatrics Infectious Diseases

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25760565 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir; Zidovudine; Stavudine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Clinical Trial Disclosures & Transparency
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2007
• First Posted: September 14, 2007
• Study Start: December 28, 2006
• Primary Completion: April 6, 2009
• Study Completion: August 16, 2017
• Last Updated: March 14, 2018
• Results First Posted: March 22, 2012

Record last verified: 2018-02

Locations

PA (1); GB (2); US (6)