| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus (Type 1) Infection |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020192 |
| E.1.2 | Term | HIV-1 |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 the efficacy of a single tablet regimen of emtricitabine/rilpivirine/tenofovir
disoproxil fumarate (FTC/RPV/TDF) compared with a single tablet regimen of
efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF, [Atripla®]) in
HIV-1 infected, antiretroviral treatment-naïve adult subjects as determined by the
achievement HIV-1 RNA < 50 copies/mL at 48 weeks; FDA snapshot analysis. |
|
| E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy, safety and tolerability of the two treatment regimens through 96 weeks of treatment,
-To assess change from baseline CD4 count in each treatment arm at 48 & 96 weeks,
-To assess genotypic and phenotypic resistance at time of virologic failure,
-To evaluate the change from baseline in fasting lipid parameters (total cholesterol, LDL and HDL cholesterol, triglycerides) at 48 & 96 weeks. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:
•The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
•Plasma HIV 1 RNA levels ≥ 2,500 copies/mL at screening
•No prior use of any approved or experimental anti-HIV drug for any length of time.
•Screening genotype report showing sensitivity to EFV, FTC, TDF, and lack of the RPV mutations K101E/P, E138A/G/K/Q/R, Y181C/I/V, and H221Y
•Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
•Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
•Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
•Adequate hematologic function (absolute neutrophil count ≥ 750/mm3; platelets ≥ 50,000/mm3; hemoglobin ≥ 8.5 g/dL)
•Serum amylase ≤ 5 x ULN (subjects with serum amylase > 5 x ULN will remain eligible if serum lipase is ≤ 5 x ULN)
•Adequate renal function:
Estimated glomerular filtration rate ≥ 50 mL/min according to the Cockcroft Gault formula:
Male: ((140 – age in years) x (wt in kg))/ (72 x (serum creatinine in mg/dL)) = CLcr (mL/min)
Female: ((140 – age in years) x (wt in kg) x 0.85) / (72 x (serum creatinine in mg/dL) = CLcr (mL/min)
•Females of childbearing potential (as defined in Section 7.8.1) must agree to utilize protocol-recommended methods of contraception highly effective contraception (as defined in Section 7.8.1), or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study period and for 12 weeks following the last dose of study drug.
Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
Female subjects who have stopped menstruating for < 12 months, or serum follicle stimulating hormone level is not within the post-menopausal range must agree to utilize protocol recommended methods of contraception.
•Male subjects must agree to utilize protocol recommended methods of contraception (as defined in Section 7.8.2) during heterosexual intercourse from the screening visit, throughout the duration of the study and for 12 weeks following discontinuation of investigational medicinal product, or be non-heterosexually active or practice sexual abstinence. .
• Adult (≥ 18 years) males or non-pregnant females
|
|
| E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria are not to be enrolled in (or may be discontinued from) this study:
•A new AIDS defining condition diagnosed within the 30 days prior to screening (refer to Appendix 5)
•Females who are breastfeeding
•Positive serum pregnancy test (female of childbearing potential)
•Proven acute hepatitis in the 30 days prior to study entry.
•Subjects receiving drug treatment for Hepatitis C, or subjects who are anticipated to receive treatment for Hepatitis C during the course of the study.
•Have a history of ongoing active liver disease or experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
•Have an implanted defibrillator or pacemaker
•Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance.
•A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Subjects with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline and must not be anticipated to require systemic therapy during the study.
•Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline. (e.g. requiring inpatient treatment or prolonged outpatient intravenous infusion therapy, exception: intramuscular penicillin for treatment of syphilis).
•Subjects receiving ongoing therapy or anticipated to need to initiate drugs or herbal/natural supplements during the study that are contraindicated or not recommended for use as indicated in the table below, including drugs not to be used with FTC, EFV, RPV, TDF, and Atripla (refer to the individual agent’s Prescribing Information); or subjects with known allergies to the excipients of the FTC/RPV/TDF single tablet regimen and/or Atripla tablets.
Drug Class Agents Disallowed*
Analeptics: Modafinil
Antiarrhythmics: Bepridil
Anticonvulsants: Phenobarbital, carbamazepine, oxcarbazepine, and phenytoin
Antibiotics: Rifabutin, rifampin, rifapentine, telithromycin, troleandomycin
Antibacterials: Telithromycin
Antidiabetics: Pioglitazone, troglitazone
Antifungals: Voriconazole
Antihistamines: Astemizole, Terfenadine
Antimycobacterials: Rifampin, Rifapentine, Rifabutin
Calcium Channel Blockers: Bepridil
GI Motility Agents: Cisapride
Glucocorticoids (systemic): Dexamethasone Ergot Derivatives: Ergotamine, Ergonovine, Dihydroergotamine, Methylergonovine
Herbal/Natural Supplements: St. John’s Wort, Echinaccea
Progestogens: Megestrol Acetate
Proton Pump Inhibitors: Omeprazole, lansoprazole, rabeprazole, pantoprazole, esomeprazole
Neuroleptics: Pimozide
Sedatives/Hypnotics: Midazolam, Triazolam
* Administration of any of the above medications must be discontinued at least 21 days prior to the Baseline/Day 1 visit and for the duration of the study.
•Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial.
•Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids for immunosuppression during the study (e.g., corticosteroids, immunoglobulins, and other immune- or cytokine based therapies).
•Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the FDA snapshot analysis. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The secondary objectives of this study are:
• To evaluate the efficacy, safety and tolerability of the two treatment regimens through 96 weeks of treatment,
• To assess change from baseline CD4 count in each treatment arm at 48& 96 weeks,
• To assess genotypic and phenotypic resistance at time of virologic failure,
• To evaluate the change from baseline in fasting lipid parameters (total cholesterol, LDL and HDL cholesterol, triglycerides) at 48 & 96 weeks. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Any point of virologic failure, week 48 and week 96 |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| 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 | 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| 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.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 48 |
| 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 | No |
| 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 |
| Australia |
| Austria |
| Belgium |
| Canada |
| France |
| Germany |
| Italy |
| Netherlands |
| Portugal |
| Puerto Rico |
| Spain |
| Switzerland |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
After Week 96, subjects in countries where the FTC/RPV/TDF STR is not commercially available at the end of the 96 week visit will be given the option to receive the STR until it becomes commercially available, or until Gilead Sciences elects to terminate development of the STR in that country.
Subjects continuing on the STR will not complete the 30-day follow-upvisit and will continue with study visits every 12 weeks. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
