E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus, Type 1 (HIV-1) Infection |
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E.1.1.1 | Medical condition in easily understood language |
Human Immunodeficiency Virus, Type 1 (HIV-1) Infection |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
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 |
Part A:
To evaluate the steady state pharmacokinetics (PK) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) single tablet regimen (STR) in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents.
Part B:
To evaluate the safety and tolerability of the EVG/COBI/FTC/TDF STR through Week 48 in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the antiviral activity of the EVG/COBI/FTC/TDF STR through Week 48 in HIV-1 infected, ARV treatment-naive adolescents. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 12 years to < 18 years of age at Baseline
- 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 of ≥ 1,000 copies/mL at screening (Roche COBAS TaqMan v2.0)
- CD4+ cell count > 100 cells/μL
- Weight ≥ 35 kg (77 lbs)
- Screening genotype report provided by Gilead Sciences must show sensitivity to FTC and TDF using the GenoSure RT/PR assay
- Able to swallow oral tablets
- Adequate renal function: Estimated glomerular filtration rate ≥ 90 mL/min/1.73m2 (using Schwartz Formula)
- Clinically normal ECG (or if abnormal, determined by the investigator to be not clinically significant)
- Documented screening for active pulmonary tuberculosis per local standard of care within 6 months of a screening visit
- Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- Subjects with a positive Hepatitis B surface antigen screening test can participate in the study, providing that alternate therapy (other than TDF) for chronic Hepatitis B infection is available to the subjects as a part of local standard of care
- 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
- Male and female subjects of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse throughout the study period and for 30 days 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. It is recommended that an oral contraceptive contain at least 30 μg of ethinyl estradiol if administered with EVG/COBI/FTC/TDF STR.)
- Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product
- Must be willing and able to comply with all study requirements
- Life expectancy ≥ 1 year.
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E.4 | Principal exclusion criteria |
- A new AIDS-defining condition (CDC 1993 case definitions, with the exception of CD4+ cell count criteria) diagnosed within the 30 days prior to screening.
- Prior treatment with any approved or investigational or experimental anti HIV-1 drug for any length of time (other than that given for prevention of mother-to-child transmission)
- Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit.
- 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 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.
- 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 without prior approval from sponsor is prohibited while participating in this trial.
- Subjects receiving ongoing therapy with any of the medications listed in the table within the exclusion criteria section of the protocol (Protocol Section 4.3), including drugs not to be used with EVG, COBI, FTC, TDF or subjects with any known allergies to the excipients of EVG/COBI/FTC/TDF STR tablets.
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A:
PK parameter of AUCtau for EVG
Part B:
Incidence of treatment-emergent SAEs and all treatment-emergent adverse events.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Part A: Day 10
- Part B: Baseline to Week 48 plus 30 days follow-up |
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E.5.2 | Secondary end point(s) |
Part A
PK parameters of Ctau and Cmax for EVG, AUCtau, Cmax, and Ctau for FTC, TFV and COBI.
Part B:
- The percentage of subjects with plasma HIV-1 RNA < 50 copies/mL at Weeks 24 and Week 48 as defined by the FDA snapshot analysis
- The percentage of subjects with plasma HIV-1 RNA < 400 copies/mL at Weeks 24 and 48 as defined by the FDA snapshot analysis
- The change from baseline in plasma log10 HIV-1 RNA (copies/mL) and in CD4+ cell count (cells/μL) and percentage at Weeks 24 and 48
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Part A: Day 10
- Part B: Week 24 and 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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Other health-related outcomes. |
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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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 |
Thailand |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial months | 2 |