| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10000807 |
| E.1.2 | Term | Acute HIV infection |
|
| 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 | 10008919 |
| E.1.2 | Term | Chronic HIV infection |
|
| 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 |
| The primary objective of the trial is to demonstrate non-inferiority of treatment with TMC278 when administered as 25 mg q.d. compared to the control group (EFV) in regard to the proportion of virologic responders (plasma viral load < 50 HIV-1 RNA copies/mL, according to TLOVR algorithm) at 48 weeks in ARV-naïve HIV-infected subjects, with a maximum allowable difference of 12%. |
|
| E.2.2 | Secondary objectives of the trial |
| to demonstrate non-inferiority of TMC278 compared to control (EFV) with a maximum allowable difference of 10% at 48 weeks for the primary efficacy endpoint (proportion of subjects achieving confirmed virologic response, defined as a confirmed plasma viral load < 50 HIV-1 RNA copies/mL [TLOVR] at 48 weeks treatment); - to evaluate superiority in efficacy of TMC278 compared to control (EFV), in case non-inferiority is established; 0083677, Final, 15-Oct-2007 17:04 TMC278-TiDP6-C209 Revised Clinical Trial Protocol 17 - to evaluate and compare the safety and tolerability of TMC278 when administered as 25 mg q.d. versus control (EFV) over 48 and 96 weeks; - to evaluate and compare the antiviral activity of TMC278 when administered as 25 mg q.d. versus control (EFV) over 48 and 96 weeks; - to evaluate and compare immunologic changes (as measured by CD4+ cell count) in the TMC278 group versus those in the control group (EFV) over 48 and 96 weeks; - to assess the evolu |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI: Sotto-studio Dexascan
|
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| E.3 | Principal inclusion criteria |
| Male or female subjects, aged 18 years or older; 0083677, Final, 15-Oct-2007 17:04 TMC278-TiDP6-C209 Revised Clinical Trial Protocol 22 2. Subject with documented HIV-1 infection; 3. Subject has signed the ICF voluntarily; 4. Subject can comply with the protocol requirements; 5. Subject has never been treated with a therapeutic HIV vaccine or an ARV drug prior to screening; 6. HIV-1 plasma viral load at screening is ≥ 5,000 HIV-1 RNA copies/mL (assayed by RNA PCR standard specimen procedure); 7. 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; 8. Demonstrated sensitivity to TDF and FTC based on results at screening or based on available historical data, when using the lower clinical cut-off (indicated as “Maximal Response”) or the biological cut-off (indicated as “susceptible”) on the screening vircoTYPE HIV-1 result; 9. Subject agrees not to start ART before the baseline visit; 10. Subject’s 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 |
| Any previous treatment with a therapeutic HIV vaccine or use of ARVs, including use of NVP for the prevention of vertical HIV transmission; 2. Having documented genotypic evidence of NNRTI resistance at screening or from historical data available in the source documents, i.e., at least one of the NNRTI RAMs from the following list: A098G L100I K101E K101P K101Q K103H K103N K103S K103T V106A V106M V108I E138G E138K E138Q V179D V179E Y181C Y181I Y181V Y188C Y188H Y188L G190A G190C G190E G190Q G190S G190T P225H F227C M230I M230L P236L K238N K238T 3. Previously documented HIV-2 infection; 4. Use of disallowed concomitant therapy from 4 weeks prior to baseline visit (see Section 5.3.13); 5. 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; 6. Life expectancy less than 6 months; 7. Subject has any currently active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions: - 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. If the subject is on maintenance therapy (which may include human Growth Hormone, appetite stimulants, and anabolic steroids) for previously diagnosed wasting syndrome, he/she may be eligible for the trial only if such treatment is not included in the list of disallowed medications; - Pneumocystis Carinii Pneumonia (PCP) infection that is considered cured and the acute phase ended at least 30 days ago, and for which currently no therapeutic treatment is required (PCP prophylaxis is allowed, as long as it is not included in the list of disallowed medications); - Past occurrence of cryptococcosis that is considered to be fully cured and the acute phase ended at least 30 days ago, and/or for which no therapeutic treatment is required. Note: An AIDS defining illness not clinically stabilized for at least 30 days will be considered as currently active. 8. Any active clinically significant disease (e.g., pancreatitis, cardiac dysfunction, active and significant psychiatric disorder, clinical suspicion of adrenal insufficiency), or findings during screening or medical history or physical examination that in the investigator’s opinion, would compromise the outcome of the trial; 9. Subject has active tuberculosis and/or is being treated for tuberculosis at screening; Note: Subjects who develop tuberculosis during the trial will be withdrawn from the trial to allow appropriate tuberculosis therapy to be installed. 10. Subject has known or suspected acute (primary) HIV-1 infection; 11. Subject has one or more of the follwing risk factors for QTc prolongation: - A confirmed prolongation of QT/QTc interval, e.g., repeated demonstration of QTcF (Fridericia correction) interval > 450 ms in the screening ECG (i.e., retesting to reassess eligibility will be allowed once using an unscheduled visit during the screening period); - Pathological Q-waves (defined as Q-wave > 40 ms or depth > 0.4-0.5 mV); 0083677, Final, 15-Oct-2007 17:04 TMC278-TiDP6-C209 Revised Clinical Trial Protocol 24 - Evi |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective of the trial is to demonstrate non-inferiority of treatment with TMC278 when administered as 25 mg q.d. compared to the control group (EFV) in regard to the proportion of virologic responders (plasma viral load < 50 HIV-1 RNA copies/mL, according to TLOVR algorithm) at 48 weeks in ARV-naïve HIV-infected subjects, with a maximum allowable difference of 12%. |
|
| 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 | Yes |
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| REGIME FISSO DI BACKGROUND |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 46 |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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