Health Condition 1: null- HIV 1 infected adolescents
Conditions
Interventions
Intervention1: TMC 278: This is a open label study with a non-nucleotide reverse transcriptase inhibitor, so no comparators are used only TMC 278.
The study drug TMC 278 is available as 25mg oral dose
Sponsors
Johnson and johnson Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1.Boys or girls, aged 12 to 18 years. 2. Subject?s weight is more thanor equal to 32 kg. 3. Subject with documented chronic HIV-1 infection who is aware of his/her HIV-1 diagnosis. 4.Subject has,prior to screening, never been treated with a therapeutic HIV vaccine or an HIV drug with the exception of a single dose of NVP to prevent MTCT. 5. HIV-1 plasma viral load at screening 5,000 HIV1 RNA copies/mL (assayed by RNA polymerase chain reaction, standard specimen procedure). 6. In the judgment of the investigator, it is appropriate to initiate ARV therapy based on the subject?s medical condition and taking into account guidelines for the treatment of HIV-1 infection in children of this age group. Note: Most current treatment guidelines recommend considering initiation of ART when CD4+ cell counts are less than 350 cells/mm³. However, clinical situations may warrant initiating ART with CD4+ cell counts 350 cells/mm³. 7. Results from the screening virco® TYPE HIV-1 demonstrate sensitivity to the selected N(t)RTIs using the lower CCO (indicated as ?maximal response? on the screening TYPE HIV-1 result) or the BCO (indicated as ?susceptible?), whichever is applicable for the chosen background regimen. 8. The subject agrees (or their parents/caregivers agree, in case the subjects age is below the cut-off age for consent according to local regulations, in which case the subject is informed and asked to give positive assent) not to start ART before the baseline visit. 9.General medical condition, in the investigator?s opinion, does not interfere with the assessments and the completion of the trial.
Exclusion criteria
Exclusion criteria: Subjects meeting one or more of the following criteria cannot be selected: 1. Any previous use of ARVs, with the exception of a single dose of NVP to prevent MTCT. Note: Subjects who were infected by MTCT are allowed to enter, provided the mother was ARV treatment-naïve at the time of delivery with the exception of NVP for no more than 3 days. 2. Having documented genotypic evidence of NNRTI resistance at screening or from historical data available in the source documents, i.e., 1 NNRTI RAM from the following list (the list was compiled on the basis of the list of IAS-USA NNRTI RAMs23 and other relevant publications). A098G V106M Y181C G190S L100I V108I Y181I G190T K101E E138A Y181V P225H K101P E138G Y188C F227C K101Q E138K Y188H M230I K103H E138Q Y188L M230L K103N E138R G190A P236L K103S V179E G190C K238N K103T V179D G190E K238T V106A V179T G190Q Y318F 3. Previously documented HIV-2 infection. 4. Subject has a positive HLA-B5701 test at screening (when the invesigator considers ABC/3TC as a background regimen). In case of a positive test, ABC/3TC cannot be administered, but instead, the investigator can select AZT/3TC as the background regimen. HLA-B5701 testing is not required for subjects with prior documented negative results. 5. Use of disallowed concomitant therapy from 4 weeks prior to the baseline visit. 6. Any condition (including but not limited to alcohol and drug use), which, in the opinion of the investigator, could compromise the subject?s safety or adherence to the protocol. 7. Life expectancy less than 6 months. Date Subject has any currently active Acquired Immunodeficiency Syndrome (AIDS) defining illness (Category C conditions according to the Centers for Disease Control and Prevention [CDC] Classification System for HIV-Infection 1993). Note: An AIDS defining illness not clinically stabilized for at least 30 days will be considered as clinically active. Note: Primary or secondary prophylaxis for an AIDS defining illness is allowed in case the medication used is not part of the disallowed medication. 9. Any active clinically significant disease (e.g., pancreatitis, cardiac dysfunction, active and significant psychiatric disorders, clinical suspicion of adrenal insufficiency, hepatic impairment), or findings during screening or medical history that in the investigator?s opinion, would compromise the outcome of the trial. 10. Subject has a known or suspected acute (primary) HIV-1 infection. 11. Any current or history of adrenal disorder. 12. Previously demonstrated clinically significant allergy or hypersensitivity to any of the components of the investigational medication (TMC278) or the selected NRTIs. In this last case, the other N(t)RTI may be selected. 13. Receipt of any investigational drug or investigational vaccine within 90 days prior to the first administration of TMC278. 14. Pregnant or breastfeeding girl. 15. Heterosexually active girls of childbearing potential without the use of effective birth control methods or not willing to continue practicing these birth control methods from screening onwards until at least 30 days after last intake of TMC278. Girls of childbearing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the steady-state pharmacokinetics of TMC278 25 mg q.d. or weight-adjusted dose of TMC278 in subjects aged?n12 to 17 years - to evaluate short-term for 2 weeks safety, and antiviral activity of TMC278 in this age group. The objectives of Part 2 are - To evaluate long-term safety and efficacy of TMC278 over a 24 and 48 week treatment periodTimepoint: To evaluate the steady-state pharmacokinetics of TMC278 25 mg q.d. or weight-adjusted dose of TMC278 in the first 2 weeks of treatment and this will be followed up for till week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate immunologic changes (as measured by CD4+ cell parameters) over 24 and 48 weeks of treatment with TMC278; - to assess the evolution of viral genotype and phenotype over 24 and 48 weeks of treatment with TMC278 - to evaluate pharmacokinetics by means of population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for safety and efficacy of TMC278 - to evaluate treatment adherence as measured by the Study Adherence Questionnaire for Children and TeenagersTimepoint: This will be verified through the 48wks on the study | — |
Countries
India, South Africa, Thailand, Uganda, United States of America
Contacts
Public ContactSindhu John
Outcome results
None listed