Ensayo fase II, abierto, de un solo brazo de tratamiento para evaluar la farmacocinética, seguridad, tolerabilidad y actividad antiviral de TMC278 en pacientes adolescentes de entre 12 y 18 años de edad infectados por el VIH-1, sin tratamiento antirretroviral previo.A Phase II, open label, single arm trial to evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of TMC278 in antiretroviralnaïve HIV-1 infected adolescents aged 12 to < 18 years

• Conditions: HIV-1 Infection; MedDRA version: 9.1Level: LLTClassification code 10020161Term: HIV infection

• Registration Number: EUCTR2008-001696-30-ES
• Lead Sponsor: Tibotec Pharmaceuticals Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-10-30
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

Subjects who meet all of the following criteria are eligible for this trial:
1. Boys or girls, aged = 12 to <18 years.
2. Subject’s weight is = 40 kg.
3. Subject with documented chronic HIV-1 infection who is aware of his/her HIV-1
diagnosis.
4. Subject willing and able to give consent. In case the subject’s age is below the cut-off age for consent (according to local regulations), their parent/caregiver should be able and willing to give consent, and the subject will be informed about the trial and asked to give positive assent.
5. Subject can comply with the protocol requirements.
6. 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.
7. HIV-1 plasma viral load at screening = 5,000 HIV-1 RNA copies/mL (assayed by RNA
polymerase chain reaction [PCR] standard specimen procedure).
Note: To reassess eligibility, retesting of a screening value that leads to exclusion will be allowed only once during the screening period using an unscheduled visit.
8. 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 < 350 cells/mm³. However, clinical situations may warrant
initiating ART with CD4+ cell counts > 350 cells/mm³. An example of such
situations would include rapidly declining CD4+ cell counts over time.
9. 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 virco®TYPE HIV-1 result) or the BCO (indicated as susceptible”), whichever is applicable for the chosen background regimen.
10. Subject is able to swallow the TMC278 tablet as a whole (since the tablet cannot be chewed, broken, or crushed).
11. The subject agrees (or their parents/caregivers agree, in case the subject's 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.
12. General medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.
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 Y318K
3. Previously documented HIV-2 infection.
4. Subject has a positive HLA-B*5701 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-B*5701 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.8. 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).
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.
16. Heterosexually active boys without the use of effective birth control methods or not willing to continue practicing these birth control methods from screening onwards until 30 days after last intake of TMC278.
17. Any grade 3 or 4 laboratory toxicity according to the Division of AIDS (DAIDS) grading table (see Section 8.2, Addendum 2), except for:
- grade 3 absolute neutrophil count;
- grade 3 platelets;
- grade 3 glucose elevation in diabetics;
- asymptomatic grade 3 pancreatic amylase elevation;
- asymptomatic grade 3 triglyceride / cholesterol / glucose elevation;
- asymptomatic grade 4 triglyceride elevation.
18. Subject has active tuberculosis and/or is being treated for tuberculosis at screening.
19. Subject has one or more of the following risk factors for QTc prolongation:
- a confirmed pr

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified