E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus (HIV-1) Infections |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 100000004862 |
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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 |
To evaluate the safety and tolerability of E/C/F/TAF in HIV-infected virologically suppressed adolescents 12 to <18 years of age |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of switching to E/C/F/TAF in HIV-infected virologically suppressed adolescents 12 to <18 years of age. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Currently on a stable antiretroviral regimen for ≥ 6 consecutive months • 12 years to < 18 years of age • Weight ≥ 35kg (77 lbs.) • Subjects able to give written assent prior to any screening evaluations • Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements • Plasma HIV-1 RNA levels < 50 copies/mL for ≥ 6 months preceding the screening visit (measured at least twice using the same assay) and not experienced two consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year. • CD4+ cell count > 100 cells/μL • No documented history of resistance to EVG, FTC, 3TC or TFV including, but not limited to, the presence of reverse transcriptase mutations K65R, K70E, M184V/I, or 3 or more thymidine analog-associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). • Adequate renal function: Estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2 • Clinically 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) • No evidence of current HBV infection • No evidence of current HCV infection • For subjects on all agents except ATV, total bilirubin or normal direct bilirubin ≤ 1.5 mg/dL • For all subjects on ATV, total bilirubin or normal direct bilirubin ≤ 3.0 mg/dL • Adequate hematologic function (absolute neutrophil count ≥ 500/mm3; platelets ≥ 50,000/mm3; hemoglobin ≥ 8.5 g/dL) • Negative serum pregnancy test for all female subjects • Females of childbearing potential (as defined in Appendix 5) must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from Screening throughout the duration of study treatment and for 30 days following discontinuation of investigational medicinal product. • 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. • Male subjects must agree to utilize highly effective contraception methods during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from Baseline throughout the study period and for 30 days following discontinuation of investigational medicinal product. • Male subjects must refrain from sperm donation from Day -1 through completion of the study and continuing for at least 30 days from the date of last dose of study drug. • Able to swallow oral tablets • Must be willing and able to comply with all study requirements • Life expectancy > 1 year • Lactating females must agree to discontinue nursing before initiating study drug
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E.4 | Principal exclusion criteria |
• A new AIDS-defining condition diagnosed within the 30 days prior to Screening • Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of screening • Anticipated to require rifamycin treatment for mycobacterial infection while participating in the study. Note: prophylactic INH therapy for latent TB treatment is allowed. • Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.) • Pregnant or lactating subjects • Have an implanted defibrillator or pacemaker • Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol. • Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance. • Have history of significant drug sensitivity or drug allergy. • Known hypersensitivity to the study drugs, the metabolites or formulation excipients • Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study Screening or expected to receive these agents during the study • 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. • Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing. • Participation in any other clinical trial (including observational trials) without prior approval from sponsor is prohibited while participating in this trial. • Subjects receiving ongoing therapy with any of the medications specified in protocol section 4.3, including drugs not to be used with EVG, COBI, FTC, TDF and TAF
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of treatment-emergent SAEs and all treatment-emergent AEs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout duration of the study |
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E.5.2 | Secondary end point(s) |
- The percentage of subjects with HIV-1 RNA < 50 copies/mL (as defined by the US FDA-defined snapshot analysis) at Weeks 24 and 48 - The change from baseline in CD4 cell count and CD4 percentage at Weeks 24, and 48 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | Yes |
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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
South Africa |
United States |
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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.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |