| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Infección por VIH-1
HIV-1 infection |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020192 |
| E.1.2 | Term | HIV-1 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate safety and tolerability of TMC125 in combination with other ARVs over a 24-week treatment period in children aged 6 to 17 years, inclusive. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate long-term safety and tolerability of TMC125 in combination with other ARVs over a 48-week treatment period in children aged 6 to 17 years, inclusive.
- To assess population pharmacokinetic parameters and pharmacokinetic (PK) / pharmacodynamic (PD) relationships of TMC125 for antiviral activity and safety over 24 and 48 weeks of treatment in children aged 6 to 17 years, inclusive.
- To evaluate the antiviral activity of TMC125 in combination with other ARVs over a 24-week and a 48-week treatment period in children aged 6 to 17 years, inclusive.
- To evaluate immunological changes (as measured by CD4 cell count) over 24 and 48 weeks.
- To assess the evolution of the viral genotype and phenotype over 24 and 48 weeks. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects who meet all of the following criteria are eligible for this trial:
1. Male or female subjects, aged between 6 and 17 years, inclusive at signing of informed consent.
2. Body weight according to age within 10th to 90th percentile of the CDC growth chart for children.
3. Subjects (where appropriate, depending on age and local regulation) and their parent(s) or legal representative(s) willing and able to give consent. Children will be informed about the trial and asked to give assent.
4. Subjects with documented HIV-1 infection.
5. Subject can comply with the protocol requirements.
6. HIV-1 plasma viral load at screening visit above 1000 HIV-1 RNA copies/mL.
7. On a stable ART for at least 8 weeks at screening and willing to stay on that treatment until baseline.
Note: Stable ART should comprise of a combination of at least 2 ARVs in line with the Pediatric Treatment Guidelines.
8. General medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial. |
|
| E.4 | Principal exclusion criteria |
Subjects meeting 1 or more of the following criteria cannot be selected:
1. Evidence of resistance against TMC125 based on the resistance test performed at Screening. An up to date resistance interpretation will be provided to the investigator and can be used to determine eligibility in the trial.
2. Previously documented HIV-2 infection.
3. Use of disallowed concomitant therapy.
4. Life expectancy of less than 6 months, according to the judgment of the investigator.
5. Presence of any currently active AIDS defining illness with the following exceptions, which must be discussed with the Sponsor prior to enrolment:
- Stable, cutaneous Kaposi Sarcoma (i.e., no pulmonary or gastrointestinal involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the trial period;
- Wasting syndrome due to HIV infection if, in the investigator’s opinion, it is not actively progressive and its treatment does not require hospitalization or compromise the subject’s safety or compliance to adhere to the trial protocol procedures.
Note:
- An AIDS defining illness not clinically stabilized for at least 30 days will be considered as currently active.
- Primary and secondary prophylaxis for an AIDS defining illness is allowed in case the medication used is not part of the disallowed medication.
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. Any active clinically significant disease (e.g., tuberculosis (TB), cardiac dysfunction, pancreatitis, acute viral infections) or findings during screening of medical history or physical examination that, in the investigator’s opinion, would compromise the subject’s safety or outcome of the trial.
8. Acute viral hepatitis including but not limited to A, B or C.
9. Subject enrolled in other clinical trials that include any blood sampling, specimen collection, or other interventional procedure. Concurrent participation in non-interventional observational trials is allowed as long as there is no impact on the objectives of this trial.
Note: Also during the conduct of the trial, subjects are not allowed to participate in any other clinical trial that include any blood sampling, specimen collection, or other
interventional procedure.
10. Receipt of any ARV or non-ARV investigational medication or investigational vaccine within 30 days prior to screening, except for those medications where dose
recommendations for children are available and for which the use was discussed with and approved by the Sponsor.
11. Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication (TMC125).
12. Pregnant or breastfeeding female.
13. Sexually active boys, or girls who are sexually active and able to become pregnant, not using safe and effective birth control methods or not willing to continue practicing these birth control methods during the trial and until 30 days after the end of the trial (or after the last intake of the investigational medication).
14. Any grade 3 or 4 toxicity according to the Division of AIDS (DAIDS) grading scale except for:
• Grade 3 absolute neutrophil count;
• Grade 3 platelets;
• Asymptomatic grade 3 pancreatic amylase elevation;
• Asymptomatic grade 3 triglyceride / cholesterol / glucose elevation;
• Asymptomatic grade 4 triglyceride elevation.
Note: retesting of abnormal screening values that lead to exclusion will be allowed only once using an unscheduled visit during the screening period (to reassess eligibility).
Note: Subjects co-infected with chronic hepatitis B or C with AST and/or ALT < 5 x the
upper limit of normal will be allowed to enter the trial if their condition is clinically
stable and is not expected to require treatment during the trial period. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
To evaluate the safety and tolerability of TMC125 when administered at a dose of 5.2 mg/kg bid in combination with an OBR over a 24-week and 48 week treatment period in children aged 6 to 17 years, inclusive.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability; antiviral activity; immunological changes; evolution of viral genotype and phenotype |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 34 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
Print
