The purpose of this study is to assess the safety and efficacy of switching to tenofovir disoproxil fumarate (TDF) compared to continuing stavudine or zidovudine in maintaining virologic suppression in HIV-1 infected children.
- Conditions
- Human Immunodeficiency Virus-1 infectionMedDRA version: 17.1Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2007-003418-32-Outside-EU/EEA
- Lead Sponsor
- Gilead Sciences,Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 100
The following inclusion criteria will be applied to all subjects, including subjects currently
enrolled in Study GS-US-162-0111:
• Male or female
• 2 years to < 12 years of age (consent of parent or guardian required)—Subjects currently
enrolled in Study GS-US-162-0111 must be 2 to < 16 years of age. If the study drug is
not commercially available in the country where the subject is enrolled, inclusion up to
< 18 years of age at the start of participation in the extension is permitted
• Documented laboratory diagnosis of HIV infection (if no record exists, must be tested at
screening visit)
• Plasma HIV-1 RNA < 400 copies/mL
• Currently receiving stavudine or zidovudine containing antiretroviral therapy regimen for at least 12 weeks
• Naive to tenofovir DF
• Negative serum pregnancy test (post-menarchal females only)
• Male and female subjects of childbearing potential must agree to utilize highly effective
contraception methods while on study treatment or agree to abstain from heterosexual
intercourse for 30 days following the last does of study drugs; highly effective methods
normally utilize two separate forms of contraception, one of which must be an effective
barrier contraceptive method.
• Parent or guardian able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements
• Subject able to provide written assent if they have the ability to read and write
Inclusion Criteria for the First 96-Week Extension
• Completed 48 weeks of treatment in Arm 1 or Arm 2 of the study
• Continues to be < 18 years of age (consent of parent or guardian required) at the start of
participation in the extension
• Patients 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 patient. Patients will not participate in the study extension if they do not choose to receive open-label tenofovir DF.
Inclusion Criteria for the Second 96-Week Extension
• Completed 144 weeks of treatment with study drug
• Continues to be < 18 years of age (consent of parent or guardian required) at the start of participation in the extension. Not applicable in those regions where tenofovir DF is not commercially available for treatment of HIV-1 infection in adults.
Inclusion Criteria for the Third 96-Week Extension
• Completed 240 weeks of treatment with study drug
• Continues to be < 18 years of age (consent of parent or guardian required) at the start of participation in the extension. Not applicable in those regions where tenofovir DF is not commercially available for treatment of HIV-1 infection in adults.
Inclusion Criteria for the Long-Term Extension
• Completed 336 weeks of treatment with study drug and have evidence of benefit from
tenofovir DF:
— HIV-1 RNA < 400 copies/mL at the Week 336 visit, or
— At least a 1 log10 decrease in HIV-1 RNA during the study, no evidence of TDF viral resistance at or prior to Week 336, and is expected to benefit from continued TDF therapy in the opinion of the investigator
• Continues to be < 18 years of age (consent of parent or guardian required) at the start of participation in the extension.
Inclusion Criteria for the Long-Term Extension
• Completed 336 weeks of treatment with study drug and have evidence of benefit from tenofovir DF:
— HI
No exclusion criteria will be applied to subjects enrolling from Study GS-US-162-0111.
Subjects not currently enrolled in Study GS-US-162-0111 that meet any of the following exclusion criteria are not to be enrolled in this study:
• Subjects receiving didanosine as part of the background regimen
• Subjects receiving ongoing therapy with any of the following:
— Nephrotoxic agents
• Aminoglycoside antibiotics
• Cidofovir
• Cisplatin
• Foscarnet
• IV amphotericin B
• Voriconazole
• IV pentamidine
• IV vancomycin
• Oral or IV ganciclovir
• Probenecid
— Systemic chemotherapeutic agents
— Systemic corticosteroids
— Interleukin-2 (IL-2) and other immunomodulating agents
— Investigational agents (except with the expressed approval of the Sponsor)
Administration of any of the above medications must be discontinued at least 30 days prior to the Baseline Visit and for the duration of the study period.
• Pregnant or lactating subjects
• 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
subject compliance
• Malignancy other than cutaneous Kaposi’s sarcoma (KS) or basal cell carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received
any systemic therapy for KS within 30 days of baseline and are not anticipated to require systemic therapy during the study
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic therapy within 15 days prior to screening
• Prior history of significant renal disease (i.e., nephrotic syndrome, renal dysgenesis,
polycystic kidney disease, congenital nephrosis)
• Prior history of significant bone disease (i.e., osteomalacia, chronic osteomyelitis,
osteogenesis imperfecta, osteochondroses, multiple bone fractures)
• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for study or unable to comply with the dosing requirements
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of switching to tenofovir DF compared to continuing stavudine or zidovudine in maintaining virologic suppression (plasma HIV-1 RNA < 400 copies/mL) in HIV-1-infected children at Week 48. ;Secondary Objective: • To evaluate the safety and tolerability of tenofovir DF in HIV-1-infected children<br>• To evaluate the effects of switching from stavudine or zidovudine to tenofovir DF versus continuing stavudine or zidovudine on bone mineral density, fasting lipid parameters and fat distribution<br>• To evaluate the pharmacokinetics of tenofovir in a subset of HIV-1 infected children receiving tenofovir DF oral powder formulation<br>• To evaluate the long-term efficacy, safety, and tolerability of treatment with tenofovir DF.;Primary end point(s): The Primary efficacy endpoint is the proportion of subjects maintaining HIV-1 RNA <400 copies/ml at Week 48.;Timepoint(s) of evaluation of this end point: At Week 48
- Secondary Outcome Measures
Name Time Method