HIV infection MedDRA version: 9.1 Level: LLT Classification code 10020161 Term: HIV infection
Conditions
Interventions
Product Name: TMC278 (as the hydrochloric acid salt), R314585
Product Code: GFI 314585-CA-030, F008
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: rilpivirine hydrochloride
CAS Number: 7
Sponsors
Tibotec Pharmaceuticals Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects, aged 18 years or older; 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); Note: Retesting of HIV-1 plasma viral load to reassess eligibility will be allowed only once using an unscheduled visit during the screening period. 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; Note: Most current treatment guidelines recommend considering initiation of ART when CD4+ cell counts are below 350 cells/µL. However, clinical situations may warrant initiating ART with CD4+ cell counts above 350 cells/µL. Examples of such situations would include rapidly declining CD4+ cell counts over time, high plasma viral load, history of AIDS-defining illnesses, or severe symptoms of HIV infection. 8. Demonstrated sensitivity to TDF and FTC based on results from the screening virco®TYPE HIV-1 using the lower clinical cut-off (indicated as "Maximal Response" on the screening virco®TYPE HIV-1 result) and available historical data; 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes 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
Exclusion criteria: 1. 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 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 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 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 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 infection that is considered cured, 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/or for which no therapeutic treatment is required 8. Any active clinically significant disease (e.g., pancreatitis), 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 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 - 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 second or third degree heart block - Intraventricular conduction delay with QRS duration > 120 ms - Bardyacardia 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 torsade de points (e.g., heart failure, hypokalemia) 12. Receipt of any investigational drug or investigational vaccine within 90 days prior to the first trial drug administration 13. 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 t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to demonstrate non-inferiority of treatment with TMC278 when administered as 75 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%.;Secondary Objective: -demonstrate non-inferiority of TMC278 compared to control (EFV) -evaluate superiority in efficacy of TMC278 compared to control, in case of non-inferiority -evaluate and compare safety and tolerability of TMC278 when administered as 75 mg q.d. versus control over 48 and 96 weeks -evaluate and compare antiviral activity of TMC278 when administered as 75 mg q.d. versus 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 pharmacokinetic/pharmacodynamic 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;Primary end point(s): The primary objective of the trial is to demonstrate non-inferiority of treatment with TMC278 when administered as 75 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%. | — |
Countries
Austria, Denmark, France, Italy, Netherlands, Portugal, Spain, Sweden, United Kingdom
Outcome results
None listed