Evaluation of 3TC or FTC Mono-therapy Compared to Continuing HAART as a Bridging Strategy (P1094)

This study has been terminated.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01338025
First received: April 16, 2011
Last updated: March 26, 2014
Last verified: March 2014

April 16, 2011
March 26, 2014
March 2011
May 2013   (final data collection date for primary outcome measure)
Time to development of immunologic deterioration [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]

Immunologic deterioration will be declared for a subject if any one of the following conditions is observed within the first 28 weeks:

  • greater than or equal to 30% decline in absolute CD4+ T cell count, or
  • development of CDC class C events.

Results report percent of participants reaching immunologic deterioration by week 28 calculated using the Kaplan-Meier method.

Time to development of immunologic deterioration [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Immunologic deterioration will be declared for a subject if any one of the following conditions is observed within the first 24 weeks:

  • greater than or equal to 30% decline in absolute CD4+ T cell count, or
  • a drop in CD4+ T cell count to less than 200 cells/mm3, or
  • development of CDC class C events.

Results report percent of participants reaching immunologic deterioration by week 24 calculated using the Kaplan-Meier method.

Complete list of historical versions of study NCT01338025 on ClinicalTrials.gov Archive Site
  • Changes in genotypic HIV drug resistance from baseline [ Time Frame: 28 and 52 Weeks ] [ Designated as safety issue: No ]
    Measures of drug resistance include number of drugs with reduced susceptibility, type and number of mutations, level of susceptibility to 3TC.
  • Changes HIV replication capacity [ Time Frame: 28 and 52 weeks ] [ Designated as safety issue: No ]
    Changes HIV replication capacity as measured by a change in the replication capacity measure.
  • Changes in CD4 percent and CD4+ T cell count [ Time Frame: 28 and 52 weeks ] [ Designated as safety issue: No ]
  • Changes in HIV-1 RNA levels [ Time Frame: 28 and 52 Weeks ] [ Designated as safety issue: No ]
  • Changes in immune activation [ Time Frame: 28 and 52 Weeks ] [ Designated as safety issue: No ]
    Measures of immune activation include CD8+/CD38+/HLA-DR+ T lymphocytes and hsCRP
  • Number and percent of subjects with adverse clinical outcomes [ Time Frame: 28 and 52 Weeks ] [ Designated as safety issue: Yes ]
    Measures of adverse clinical outcomes include new greater than or equal to Grade 3 signs, symptoms and laboratory values, new bacterial infections, hospitalizations, HIV-related and non-HIV-related morbidity.
  • Adherence as measured by 3-day recall [ Time Frame: 28 and 52 Weeks ] [ Designated as safety issue: No ]
  • Changes in genotypic HIV drug resistance from baseline [ Time Frame: 24 and 48 Weeks ] [ Designated as safety issue: No ]
    Measures of drug resistance include number of drugs with reduced susceptibility, type and number of mutations, level of susceptibility to 3TC.
  • Changes HIV replication capacity [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
    Changes HIV replication capacity as measured by a change in the replication capacity measure.
  • Changes in CD4% and CD4+ T cell count [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • Changes in HIV-1 RNA levels [ Time Frame: 24 and 48 Weeks ] [ Designated as safety issue: No ]
  • Changes in immune activation [ Time Frame: 24 and 48 Weeks ] [ Designated as safety issue: No ]
    Measures of immune activation include CD8+/CD38+/HLA-DR+ T lymphocytes and hsCRP
  • Number and percent of subjects with adverse clinical outcomes [ Time Frame: 24 and 48 Weeks ] [ Designated as safety issue: Yes ]
    Measures of adverse clinical outcomes include new greater than or equal to Grade 3 signs, symptoms and laboratory values, new bacterial infections, hospitalizations, HIV-related and non-HIV-related morbidity.
  • Adherence as measured by 3-day recall [ Time Frame: 24 and 48 Weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Evaluation of 3TC or FTC Mono-therapy Compared to Continuing HAART as a Bridging Strategy
Evaluation of 3TC or FTC Mono-therapy Compared to Continuing HAART as a Bridging Antiretroviral Strategy in Persistently Non-adherent Children, Adolescents, and Young Adults Who Are Failing HAART and Have the M184V Resistance Mutation.

The purpose of this study is to compare the use of 3TC or FTC alone vs. continuing a failing HAART regimen in HIV infected children, adolescents and young adults. The study will see if there are changes in the HIV virus and if there is a difference in immune function, viral load and medication side effects between the two groups over 28 weeks. The child will be assigned to either take 3TC/FTC alone or continue on his/her current failing HAART regimen. During the first 28 weeks of this study, if the child is randomized to the continue HAART arm, he/she will not be switched to a different or new, potentially suppressive HAART regimen, but will continue on the current failing HAART regimen. However, if continuing HAART, the child may be switched to a new regimen if the child's provider feels that it is clinically needed or the child meets certain study endpoints (e.g., drop in CD4, increase in viral load).

At the end of 28 weeks, the child will have the choice of remaining on the assigned study group medication(s) or starting a new HAART regimen prescribed by his/her doctor. Then, the child will be followed for another 24 weeks to see if there are changes in the child's virus and to compare the difference in immune function, viral load and medication side effects between the different groups.

Currently, there is no clear consensus for managing virologic failure. Generally, failure of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy due to non-adherence is associated with high rates of NNRTI resistance, while failure of protease inhibitor (PI)-based therapy due to non-adherence carries a much lower risk of PI resistance. In the setting of incomplete adherence and virologic failure despite adherence education, an optimal strategy would be one that effectively bridges the period between the cessation of the failing regimen of highly active ARV therapy (HAART) and initiation of a new HAART regimen. This would provide time for interventions to improve adherence to be effective while minimizing accumulation of additional drug resistance mutations. Given the compelling need for an effective bridging strategy, the limited evidence for the safety and efficacy of this bridging regimen, and the high level of acceptability of studying 3TC or FTC monotherapy as an effective alternative, P1094 is proposing to conduct a randomized clinical trial (RCT) comparing use of 3TC or FTC monotherapy as a short-term bridging regimen vs. continuation of non-suppressive HAART in non-adherent subjects.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Disease
  • Drug: HAART regimen
    The study participant will continue their non-suppressive HAART regimen as prescribed by their primary provider.
    Other Name: Highly active antiretrovial therapy (HAART)
  • Drug: 3TC or FTC monotherapy
    The study participant will be assigned to either 3TC/FTC monotherapy (the choice of 3TC or FTC will be left to the provider.
    Other Names:
    • Lamivudine (3TC)
    • emtricitabine (FTC)
  • Active Comparator: Arm A, non-suppressive HAART regimen

    In Step 1, subjects will be randomized to continue their non-suppressive HAART regimen.

    In Step 2, subjects will either begin a new HAART regimen, continue randomized treatment, or discontinue therapy while remaining on follow-up, as decided by their provider.

    Intervention: Drug: HAART regimen
  • Active Comparator: Arm B, 3TC or FTC monotherapy

    In step 1, subjects will be randomized to receive 3TC or FTC (the choice of 3TC or FTC will be left to the provider).

    In Step 2, subjects will either begin a new HAART regimen, continue randomized treatment, or discontinue therapy while remaining on follow-up, as decided by their provider.

    Intervention: Drug: 3TC or FTC monotherapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
33
May 2013
May 2013   (final data collection date for primary outcome measure)

Step 1 Inclusion Criteria:

  • Age greater than or equal to 8 to less than 25 years of age, at study entry
  • Documentation of HIV-1 infection defined as positive results from two samples collected at different time points
  • Treatment experienced patients must demonstrate failure on the current HAART regimen for 2 months or longer. These patients must have been on ARVs for at least a total of 6 months prior to entry. Thus, if the failing regimen is the first ARV regimen, then the patient must have been on that initial regimen for a minimum of 6 months total.
  • CD4+ T cell count greater than or equal to 100 cells/mm3 (confirmed on at least two occasions within 6 months of study entry, including the screening value)
  • Documentation of the M184V mutation on genotypic testing at any time prior to study entry
  • In the best judgment of the clinical site team, concerns about the subject's ability to adhere makes it unsuitable to initiate a new optimal HAART regimen for at least 6 months.
  • Subject has not become adherent despite site's adherence interventions
  • Female subjects of reproductive potential who engage in sexual activity that could lead to pregnancy must agree to avoid pregnancy during the entire 52 week trial and to consistently and appropriately use at least two of the following contraception methods: condoms, diaphragm or cervical cap with spermicide, IUD, hormonal-based contraception. A list of acceptable methods can be found at the FDA Birth Control Guide (http://www.fda.gov/womens).
  • Parent/legal guardian or subject able and willing to provide signed informed consent when applicable

Step 1 Exclusion Criteria:

  • Positive hepatitis B surface antigen or known active hepatitis B infection.
  • Pregnant or breastfeeding.
  • Active malignancy within the past 2 years.
  • Current immunosuppressive therapy, including the equivalent of greater than 1 mg/kg/per day or greater than 20 mg total daily dose of prednisone in the 2 weeks preceding screening. Subjects for whom long-term systemic corticosteroid therapy (greater than 2 weeks) is anticipated are excluded. [Note: non-steroidal anti-inflammatory agents and inhaled, nasal, and topical corticosteroids are not excluded as immunosuppressive therapy.]
  • Prior immunization with an HIV-specific vaccine
  • Greater than or equal to 1 CDC class C event within the past 12 months.
  • Renal disease (as defined by estimated creatinine clearance less than 50 mL/min/1.73m2 confirmed on two occasions within 3 months of screening).
  • Active opportunistic infections, including active tuberculosis (TB).
  • Current treatment for active systemic TB. If recent, infection must have completed treatment course. INH treatment for latent TB is allowed.
  • Viral load greater than 250,000 copies/mL at screening.
  • Known greater than or equal than Grade 3 of any of the following laboratory toxicities within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, AST, ALT, lipase, serum creatinine. Note: Subjects can be re-screened and enrolled if repeat value is less than Grade 3 without signs or symptoms of related organ dysfunction.
  • Known greater than or equal to Grade 4 laboratory toxicities within 30 days prior to study entry, except with approval of the study team.
  • For subjects who are not currently taking 3TC or FTC: Documented prior intolerance or adverse effect reasonably attributed to 3TC or FTC that resulted in permanent discontinuation.
  • Problems with non-adherence attributed to modifiable structural barriers, such as lack of resources (e.g., insurance, transportation).

Step 2 - Inclusion Criteria

  • Met requirements for completion of Step 1
  • Subject/guardian agree to continue participation in Step 2
  • ViroSeq assay results have been received by site and reviewed by investigator
Both
8 Years to 24 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Brazil,   Puerto Rico,   Thailand
 
NCT01338025
IMPAACT P1094, U01AI068632
Yes
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Chair: Allison L. Agwu, MD, Sc.M. Johns Hopkins University
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP