| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus (HIV-1) Infections |
|
| E.1.1.1 | Medical condition in easily understood language |
| Human Immunodeficiency Virus (HIV-1) Infections |
|
| 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 | 16.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020192 |
| E.1.2 | Term | HIV-1 |
| E.1.2 | System Organ Class | 100000004862 |
|
| 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 objectives of this study are:
•To evaluate the steady-state PK and confirm the dose of EVG/r in HIV-1 infected, antiretroviral treatment-experienced subjects 4 weeks to less than 18 years of age.
•To evaluate the safety and tolerability of EVG/r in HIV-1 infected, antiretroviral treatment-experienced subjects 4 weeks to <18 years of age. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is:
•To evaluate the antiviral activity of EVG/r in HIV-1 infected, antiretroviral
treatment-experienced subjects 4 weeks to <18 years of age who are failing their current
HAART regimen |
|
| 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.
Antiretroviral treatment-experienced, HIV-1 infected male and
female subjects 4 weeks (gestational age of at least 44 weeks)
to < 18 years of age
• Body weight at screening as follows:
o Cohort 2 – greater than 15 kg
o Cohort 3 – greater than 10.6 kg
o Cohort 4 – greater than 5 kg
• Part A: Evidence of suppressed viremia or failing a current
antiretroviral regimen as defined below.
• Part B: Evidence of failing a current antiretroviral regimen as
defined below.
Criteria for subjects with evidence of suppressed viremia (Part A
only):
• Plasma HIV-1 RNA concentration (at least 2 consecutive
measurements) at an undetectable level according to the assay
being used for at least 3 months prior to screening, and HIV-1
RNA <50 copies/mL (Roche COBAS TaqMan v2.0) at
screening.
• Stable antiretroviral regimen including one of the following
PI/r for at least 3 months prior to screening: lopinavir/r
(Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or
fosamprenavir/r. Subjects undergoing dose modifications to
their antiretroviral regimen for growth or switching medication
formulations are considered to be on a stable antiretroviral
regimen.
Criteria for subjects failing a current antiretroviral regimen
(Parts A and B):
• HIV-1 RNA >1,000 copies/mL at screening
(Roche COBAS TaqMan v2.0)
• Prior treatment for HIV-1 infection, defined as 6 months of
antiretroviral treatment experience (with the exception of
Cohort 4 where less than 6 months of treatment experience is
acceptable) and at least 1 documented resistance mutation as
defined by current IAS-USA Guidelines. These resistance
mutations must be documented in a historical genotype
report(s), or in the genotype report at screening provided by
Gilead Sciences.
• Stable antiretroviral regimen (or no antiretroviral regimen) for
at least 30 days prior to screening. Subjects undergoing dose
modifications to their antiretroviral regimen for growth or
switching medication formulations are considered to be on a
stable antiretroviral regimen.
• Screening genotype must show full sensitivity to EVG.
• Ability to construct a BR that must contain one of the
following fully active PI/r: lopinavir/r (Kaletra), atazanavir/r,
darunavir/r, tipranavir/r, or fosamprenavir/r. (Fully active is
defined by genotypic analysis.)
• Genotypic sensitivity score (GSS) of at least 2 (including the
fully active PI/r and EVG).
• Adequate renal, hematologic, and hepatic function.
• No opportunistic infection within 30 days of study entry. |
|
| E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
• Subjects with the following CD4+ cell counts:
— For Cohorts 1 and 2: Screening CD4+ cell count
< 50 cells/mm3
— For Cohort 3: Screening CD4+ cell count < 75 cells/mm3
— For Cohort 4: Screening CD4+ cell count < 200 cells/mm3
Evidence of active pulmonary or extra-pulmonary tuberculosis
disease:
— Within 3 months of the Screening visit for all subjects
6 months of age or older
— At any time for subjects younger than 6 months
• An ongoing serious infection requiring systemic antibiotic
therapy at the time of screening
• An acquired immunodeficiency syndrome (AIDS)-defining
condition with onset within 30 days prior to screening
• Life expectancy of < 1 year
• For subjects with HIV-1 RNA >1,000 copies/mL at screening,
prior treatment of any duration with an integrase strand transfer
inhibitor.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoints of this study are Pharmacokinetic (PK) parameters AUCtau and Cmax of EVG and the incidence of treatment-emergent AEs and treatment-emergent laboratory abnormalities
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetic (PK) parameters AUCtau and Cmax of EVG- timepoint of evaluation Day 10
Incidence of treatment-emergent AEs and treatment-emergent laboratory abnormalities- timepoint through to week 48
|
|
| E.5.2 | Secondary end point(s) |
The secondary endpoints of this study are:
•PK parameters Ctau, CL/F, and Vz/F of EVG
•The percentage of subjects with plasma HIV 1 RNA <50 and <400 copies/mL at Weeks 24 and 48 as defined by the FDA snapshot analysis, respectively
•The change from baseline in plasma log10 HIV 1 RNA (copies/mL), in CD4+ cell count (cells/μL), and CD4 percentage at Weeks 24 and 48
•Tanner Stages at Weeks 24 and 48, and age of first menses.
•Palatability of oral suspension formulation of EVG in appropriate age group
•Adherence to EVG |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoint(s) of evaluation are;
•PK parameters Ctau, CL/F, and Vz/F of EVG- timepoint Day 10
•The percentage of subjects with plasma HIV 1 RNA <50 and <400 copies/mL at Weeks 24 and 48 as defined by the FDA snapshot analysis, respectively
•The change from baseline in plasma log10 HIV 1 RNA (copies/mL), in CD4+ cell count (cells/μL), and CD4 percentage at Weeks 24 and 48
•Tanner Stages at Weeks 24 and 48, and age of first menses.
•Palatability of oral suspension formulation of EVG in appropriate age group- through to week 48
•Adherence to EVG- through to week 48 |
|
| 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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | 13 |
| 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 |
| France |
| Germany |
| Italy |
| Mexico |
| South Africa |
| Spain |
| Thailand |
| Uganda |
| United Kingdom |
|
| 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
|
Part A subjects with suppressed viremia, the end of study is defined as the completion of Day 10 & the 30-Day Follow-up visit.
For subjects failing a current antiretroviral regimen, the end of study is defined as the completion of 48 weeks on study drug & the 30-Day Follow-up visit.
For extension phase end of trial is when a) subject turns 18 & EVG is available for use in adults or b) the age appropriate EVG formulation becomes available or c) Sponsor elects to terminate development of EVG. |
|
| 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 | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
