E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10020161 |
E.1.2 | Term | HIV infection |
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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%. |
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E.2.2 | Secondary objectives of the trial |
-demonstrate non-inferiority of TMC278 compared to control (EFV) with a maximum allowable difference of 10% at 48 weeks for the primary efficacy endpoint. -evaluate superiority in efficacy of TMC278 compared to control, in case of non-inferiority is established. -evaluate and compare safety and tolerability of TMC278 when administered as 25 mg q.d. vs control over 48 and 96 weeks -evaluate and compare antiviral activity of TMC278 when administered as 25 mg q.d. vs control over 48 and 96 weeks -evaluate and compare immunologic changes in TMC278 group versus those in control group over 48 and 96 weeks -assess evolution of viral genotype and phenotype over 48 and 96 weeks -evaluate population pharmacokinetics and PK/PD relationships for efficacy and safety of TMC278. -assess preference-based health states and medical resource utilization for use in future economic evaluations -assess treatment adherence as measured by Modified Medication Adherence Self-Report Inventory |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects, aged 18 years or older; 2. S (subject) with documented HIV-1 infection; 3. S has signed the ICF voluntarily; 4. S can comply with the protocol requirements; 5. S 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 7. In the judgment of the inv, 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 or the biological cut-off on the screening virco®TYPE HIV-1 result; 9. S agrees not to start ART before the baseline visit; 10. S’s general medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial. |
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E.4 | Principal exclusion criteria |
1. Any previous treatment with a therapeutic HIV vaccine or use of ARVs, incl. use of NVP for the prevention of vertical HIV transmission 2. Having documented genotypic evidence of NNRTI resistance at screening or from historical data avail. in the source docs, i.e. at least 1 of the NNRTI RAMs from follow. list: A098G L100I K101E K101P K101Q K103H K103N K103S K103T V106A V106M V108I E138A E138G E138K E138Q E138R V179D V179E Y181C Y181I Y181V Y188C Y188H Y188L G190A G190C G190E G190Q G190S G190T P225H F227C M230I M230L P236L K238N K238T Y318F 3. Previously documented HIV-2 infection 4. Use of disallowed concomitant therapy from 4 weeks prior to baseline visit 5. Any condition which, in the opinion of the inv., could compromise the S’s safety or adherence to CTP 6. Life expectancy < 6 months 7. S has any currently active AIDS defining illness with follow. 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 trial period - Wasting syndrome due to HIV infection if, in the inv.’s opinion, it is not actively progressive and its treatment does not require hospitalization or compromise the s’s safety or compliance to adhere to CTP procedures. If the S is on maintenance therapy for previously diagnosed wasting syndrome, (s)he may be eligible for the trial only if such treatment is not incl. in list of disallowed medications - Pneumocystis Carinii Pneumonia infection that is considered cured and the acute phase ended at least 30 days ago, and for which currently no therapeutic treatment is required - 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 8. Any active clinically significant disease (eg. pancreatitis, cardiac dysfunction, active and significant psychiatric disorder, clinical suspicion of adrenal insufficiency, hepatic impairment), or findings during screening or medical history or physical examination that in the inv.’s opinion, would compromise the outcome of the trial 9. S has active tuberculosis and/or is being treated for tuberculosis at screening 10. S has known or suspected acute HIV-1 infection 11. S has one or more of follow. risk factors for QTc prolongation: - A confirmed prolongation of QT/QTc interval, eg. repeated demonstration of QTcF interval > 450 ms in the screening ECG - Pathological Q-waves - Evidence of ventricular pre-excitation - Electrocardiographic evidence of complete or incomplete left bundle branch block or right bundle branch block - Evidence of 2nd or 3rd degree heart block - Intraventricular conduction delay with QRS duration > 120 ms - Bradycardia as defined by sinus rate < 50 bpm - Personal or family history of long QT syndrome - Personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, with the exception of sinus arrhythmia - Syncopal episodes - Risk factors for Torsades de Pointes (eg. heart failure, hypokalemia, hypomagnesemia) 12. Receipt of any investigational drug or investigational vaccine within 90 days prior to first trial drug administration 13. S enrolled in other clinical trials that incl. 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 objectives of this trial. Data collected in this trial can be reported in the observ. trial 14. Previously demonstrated clinically significant allergy or hypersensitivity to any of the components of the investigational medication or to components of EFV or TDF/FTC 15. Pregnant or breastfeeding female 16. Female of childbearing potential without use of effective birth control methods or not willing to continue practising these birth control methods from screening onwards until at least 30 days after last intake of study medic. 17. Non-vasectomized heterosexually active males without use of effective birth control methods or not willing to continue practising these birth control methods from screening onwards until 30 days after last intake of study medic. 18. Any grade 3 or 4 laboratory toxicity according to the Division of AIDS grading table, except: - 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 (including LDL cholesterol)/ glucose elevation - asymptomatic grade 4 triglyceride elevation 19. Renal impairment: calculated creatinine clearance (CLCr) < 50 mL/min 20. S has clinical or laboratory evidence of significantly decreased hepatic function or decompensation (albumin < 30 g/L or bilirubin ≥ 2.5 x upper limit of laboratory normal range [ULN]), irrespective of liver enzyme levels |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with confirmed and sustained plasma viral load <50 HIV-1 RNA copies/mL (TLOVR algorithm) at Week 48. |
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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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability, durability of antiviral activity |
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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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 3 |
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 |
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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
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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 | 4 |
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 |