Ignite Creation Date:
2024-05-06 @ 1:54 AM
Last Modification Date:
2024-10-26 @ 11:11 AM
Study NCT ID:
NCT01928407
Status:
COMPLETED
Last Update Posted:
2018-01-12
First Post:
2013-06-19
Brief Title:
Evaluation of the Efficacy and Safety Between Two Antiretroviral Regimens in HIV-1-infected Treatment-naïve Subjects With Low CD4 Counts
Sponsor:
Institut de Médecine et dEpidémiologie Appliquée - Fondation Internationale Léon MBa
Organization:
Institut de Médecine et dEpidémiologie Appliquée - Fondation Internationale Léon MBa
Study Overview
Official Title:
A Phase IV Prospective Multicenter Randomized Open Label 48 Weeks Study to Evaluate the Antiretroviral Efficacy and Safety of Atazanavir or DarunavirEach in Combination With a Fixed Dose of Tenofovir Emtricitabine in HIV-1-infected Treatment-naïve Subjects With CD4counts Below 200 µL
Status:
COMPLETED
Status Verified Date:
2018-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DATA
Brief Summary:
A phase IV prospective multicenter randomized open label 48 weeks study to evaluate the antiretroviral efficacy and safety of atazanavirritonavir or darunavirritonavir each in combination with a fixed dose of tenofovir disoproxil fumarate- emtricitabine in HIV-1-infected treatment-naïve subjects with CD4 counts below 200 µL
Detailed Description:
Principal objective
To evaluate the virological efficacy and safety at week 48 of 2 regimens atazanavirritonavir ATZr 300100 mg or darunavirritonavir DRVr 800100 mg each in combination with a fixed-dose of tenofoviremtracitabine in HIV-1 treatment-naïve subjects with CD4 counts below 200 µL
Secondary objectives
Proportion of subjets with virologic efficacy at week 24
Proportion of subjects with confirmed virologic failure at week 24 or later
Proportion of patients with virologic mutations
Evaluate the virologic effect in seminal fluid
To evaluate immunological response over time up to week 48
To assess plasma and seminal pharmacokinetics of the drugs in the treatment regimen at week 4 24 and 48
Correlate the pharmacokinetic properties of the drugs with virologic outcome in plasma and semen at week 4 and 48
Correlate the free fraction not bound to protein of atazanavir and darunavir in plasma and semen to virologic outcome
Evaluate the relationship of bilirubinemia with atazanavir
Change from baseline in fasting lipids fasting glucose and insulin over time in the 2 arms
Compare adherence patient satisfaction and sexual behaviour between the regimens
Methodology
This is a 48 week multicentre prospective open label phase IV randomized non comparative study
Inclusion criteria
Male or female aged 18 years of age
HIV-1 infection determined by a positive ELISA and confirmed by Western blot
Plasma HIV-RNA 1 000 cmL
CD4T cell count 200 cellsmm3 at the time of screening or 250 cellsmm3 if the CD4 count was 200 cellsmm3 12 weeks before screening
Women of childbearing potential must agree to use an effective method of barrier contraception or have documented sterility
Subjects must have medical insurance throught the Securite Sociale
Ability to understand and provide written informed consent
Non-inclusion criteria
Acute opportunistic infection within the past two weeks
HIV-2 infection
pregnant woman
Any subject with drug resistance mutations at screening
Any subject with a grade 3 or greater clinical or laboratory adverse event at screening
Any subject who has received antiretoviral therapy except for prevention of mother to child transmission and patients who has received post exposure prophylaxis for a a month or less
calculated creatinine clearance 60mL as estimated by the Cockcroft- Gault equation
Patients in the opinion of the investigator that are unlikley to be able to follow study instructions
Any subject unable to take antiretroviral medication for whatever reason
Any subject taking a treatment or medication that is contraindicated when co-administered with any arm or drug in the treatment
Treatment
Group 1 ATV TDFFTC or AbacavirLamivudine ABC3TC if TDFFTc contre-indicated
atazanavirritonavir 300100mgday and TDFFTC 245 200 mg by day 3 pills once a day during 48 weeks during a meal
Group 2 DRV TDFFTC or ABC3TC if TDFFTc contre-indicated
darunavirritonavir 800100mgday and TDFFTC 245 200 mg by day 4 pills once a day during 48 weeks during a meal
Primary Endpoints
Proportion of patients with HIV-1 plasma viral load below 50 copiesmL at week 48 while receiving their initial regimen
Proportion of patients experiencing grade 2-4 adverse clinical and laboratory events including hematology chemistry lipids total cholesterol HDL cholesterol LDL cholesterol triglycerides glucose and insulin by week 48
Secondary endpoints
Proportion of patients with plasma HIV RNA below 50 cpmL at week 24
Proportion of patients with HIV RNA 50 cpmL at week 24 or later confirmed by a second HIV RNA at least 14 days after the first test
Development of resistance mutations in subjects who have virologic failure testing at 24 weeks or later tested by a genotypic resistance test
Evaluate the virologic effect in seminal fluid at baseline W4 and W48 by change in HIV RNA concentrations in semen over time
To evaluate immunological response over time up to week 48 in the 2 arms by CD4 cell count W-4 W2W4 W12 W36 and W48 differenciation and activation in T CD4 W2W4 W12 W24 and W48 Change in lymphocyte subset reconsistution at week 48 compared to baseline Change in immunolgic markers of inflammations at weeks 2 4 12 24 48
To assess plasma and seminal pharmacokinetics of the drugs in the treatment regimen at week 4 24 and 48 through residual concentrations C min of antiretroviral drugs at W4 W24 and W48
Atazanavir and darunavir plasma and seminal drug concentrations and coorelation with adverse clinical and laboratory events
Evaluate the relationship of bilirubinemia with atazanavir pharmacokinetics Cmin
Evolution of lipid glucose and insulin parameters from baseline to weeks 24 and 48
Adherence to regimen patient satisfaction and sexual behaviour between the regimens at W2W24 and W48 mesured by mettre ref
Evolution of anthropomorphic measurements from baseline to weeks 24 48
Substudies Brief description 2 lines maximum and person in charge of the substudy
Immunologic substudy Pr Brigitte Autran Change in immunolgic markers of inflammations at weeks 2 4 12 24 48 and change in lymphocyte subset reconsistution at week 48 compared to baseline
Pharmacologic substudy Dr Gilles Peytavin To assess plasma and seminal pharmacokinetics of the drugs in the treatment regimen at week 4 24 and 48 through residual concentrations C min of antiretroviral drugs at W4 W24 and W48
Virologic substudy Dr Anne Geneviève Marcelin Evaluate the virologic effect in seminal fluid at baseline W4 and W48
Behaviour substudy Dr France Lert Compare adherence patient satisfaction and sexual behaviour between the regimens at W2W24 and W48
Estimated enrolment 120 subjects 60 per group randomly assigned 11
To evaluate the virological efficacy and safety at week 48 of 2 regimens atazanavirritonavir ATZr 300100 mg or darunavirritonavir DRVr 800100 mg each in combination with a fixed-dose of tenofoviremtracitabine in HIV-1 treatment-naïve subjects with CD4 counts below 200 µL
Secondary objectives
Proportion of subjets with virologic efficacy at week 24
Proportion of subjects with confirmed virologic failure at week 24 or later
Proportion of patients with virologic mutations
Evaluate the virologic effect in seminal fluid
To evaluate immunological response over time up to week 48
To assess plasma and seminal pharmacokinetics of the drugs in the treatment regimen at week 4 24 and 48
Correlate the pharmacokinetic properties of the drugs with virologic outcome in plasma and semen at week 4 and 48
Correlate the free fraction not bound to protein of atazanavir and darunavir in plasma and semen to virologic outcome
Evaluate the relationship of bilirubinemia with atazanavir
Change from baseline in fasting lipids fasting glucose and insulin over time in the 2 arms
Compare adherence patient satisfaction and sexual behaviour between the regimens
Methodology
This is a 48 week multicentre prospective open label phase IV randomized non comparative study
Inclusion criteria
Male or female aged 18 years of age
HIV-1 infection determined by a positive ELISA and confirmed by Western blot
Plasma HIV-RNA 1 000 cmL
CD4T cell count 200 cellsmm3 at the time of screening or 250 cellsmm3 if the CD4 count was 200 cellsmm3 12 weeks before screening
Women of childbearing potential must agree to use an effective method of barrier contraception or have documented sterility
Subjects must have medical insurance throught the Securite Sociale
Ability to understand and provide written informed consent
Non-inclusion criteria
Acute opportunistic infection within the past two weeks
HIV-2 infection
pregnant woman
Any subject with drug resistance mutations at screening
Any subject with a grade 3 or greater clinical or laboratory adverse event at screening
Any subject who has received antiretoviral therapy except for prevention of mother to child transmission and patients who has received post exposure prophylaxis for a a month or less
calculated creatinine clearance 60mL as estimated by the Cockcroft- Gault equation
Patients in the opinion of the investigator that are unlikley to be able to follow study instructions
Any subject unable to take antiretroviral medication for whatever reason
Any subject taking a treatment or medication that is contraindicated when co-administered with any arm or drug in the treatment
Treatment
Group 1 ATV TDFFTC or AbacavirLamivudine ABC3TC if TDFFTc contre-indicated
atazanavirritonavir 300100mgday and TDFFTC 245 200 mg by day 3 pills once a day during 48 weeks during a meal
Group 2 DRV TDFFTC or ABC3TC if TDFFTc contre-indicated
darunavirritonavir 800100mgday and TDFFTC 245 200 mg by day 4 pills once a day during 48 weeks during a meal
Primary Endpoints
Proportion of patients with HIV-1 plasma viral load below 50 copiesmL at week 48 while receiving their initial regimen
Proportion of patients experiencing grade 2-4 adverse clinical and laboratory events including hematology chemistry lipids total cholesterol HDL cholesterol LDL cholesterol triglycerides glucose and insulin by week 48
Secondary endpoints
Proportion of patients with plasma HIV RNA below 50 cpmL at week 24
Proportion of patients with HIV RNA 50 cpmL at week 24 or later confirmed by a second HIV RNA at least 14 days after the first test
Development of resistance mutations in subjects who have virologic failure testing at 24 weeks or later tested by a genotypic resistance test
Evaluate the virologic effect in seminal fluid at baseline W4 and W48 by change in HIV RNA concentrations in semen over time
To evaluate immunological response over time up to week 48 in the 2 arms by CD4 cell count W-4 W2W4 W12 W36 and W48 differenciation and activation in T CD4 W2W4 W12 W24 and W48 Change in lymphocyte subset reconsistution at week 48 compared to baseline Change in immunolgic markers of inflammations at weeks 2 4 12 24 48
To assess plasma and seminal pharmacokinetics of the drugs in the treatment regimen at week 4 24 and 48 through residual concentrations C min of antiretroviral drugs at W4 W24 and W48
Atazanavir and darunavir plasma and seminal drug concentrations and coorelation with adverse clinical and laboratory events
Evaluate the relationship of bilirubinemia with atazanavir pharmacokinetics Cmin
Evolution of lipid glucose and insulin parameters from baseline to weeks 24 and 48
Adherence to regimen patient satisfaction and sexual behaviour between the regimens at W2W24 and W48 mesured by mettre ref
Evolution of anthropomorphic measurements from baseline to weeks 24 48
Substudies Brief description 2 lines maximum and person in charge of the substudy
Immunologic substudy Pr Brigitte Autran Change in immunolgic markers of inflammations at weeks 2 4 12 24 48 and change in lymphocyte subset reconsistution at week 48 compared to baseline
Pharmacologic substudy Dr Gilles Peytavin To assess plasma and seminal pharmacokinetics of the drugs in the treatment regimen at week 4 24 and 48 through residual concentrations C min of antiretroviral drugs at W4 W24 and W48
Virologic substudy Dr Anne Geneviève Marcelin Evaluate the virologic effect in seminal fluid at baseline W4 and W48
Behaviour substudy Dr France Lert Compare adherence patient satisfaction and sexual behaviour between the regimens at W2W24 and W48
Estimated enrolment 120 subjects 60 per group randomly assigned 11
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None