Induction-Maintenance With Atazanavir in HIV Naïve Patients (The INDUMA Study)

Study Overview
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Brief Summary
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The purpose of this study is to compare the proportion of subjects with HIV-1 RNA viral load < 50 c/mL through Week 48 of the Maintenance Phase among HIV-infected subjects with an initial undetectable viral load following an Induction Phase with an ATV/RTV containing HAART regimen, when switched to ATV versus remaining on ATV/RTV, whilst continuing their previous NRTI backbone.

Official Title
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A Phase IV, Open-Label, Randomized, Multicenter Trial Assessing the Efficacy of a Treatment Maintenance Phase With Unboosted vs. Boosted Reyataz After an Induction Phase With Reyataz and Ritonavir in Treatment Naive HIV Patients (the INDUMA Study)

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Atazanavir + 2 NRTIs
* Drug: Atazanavir + Ritonavir + 2 NRTIs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment naive HIV-1 infected subjects ( < 10 days of treatment with any ARV). Subjects who have an HIV-1 RNA level ≥ 5000 c/mL at screening. Subjects who have a CD4 count ≥ 50 cells/mm3. Men and women, ages 18 years of age or older (or minimum age as determined by local regulatory or as legal requirements dictate). Both females of child-bearing potential and males must utilize effective barrier contraception. Other contraception in addition to barrier methods is permitted; refer to the Investigator Brochure for details regarding potential interactions with ATV and some oral contraceptives Exclusion Criteria: WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study. WOCBP using a prohibited contraceptive method. Caution is warranted with coadministration of oral contraceptives (ethinyl estradiol and norethindrone) - see Investigator Brochure for details Women who are pregnant or breastfeeding Women with a positive pregnancy test on enrollment or prior to study drug administration. Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment Primary HIV infection Medical History and Concurrent Diseases Active alcohol or substance use sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis Physical and Laboratory Test Findings Screening laboratory values measured as follows: Grade IV glucose, Grade IV electrolytes, Grade IV transaminases, Grade IV hematology. Hypersensitivity to any component of the formulation of study drug Prior history of taking any ARV for more than 10 days Concomitant administration of tenofovir (TDF). Refer to Section 6.4.1 which details all prohibited therapies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Switch<br>ATV 400 mg + 2 NRTIs (TBD), ATV once daily, NRTIs (TBD) | Drug: Atazanavir + 2 NRTIs<br>* Capsules, tablets, Oral, 48 weeks (after a 26-to-30-week induction phase with ATV 300 mg + RTV 100 mg + 2 NRTIs)<br>* Other names: Reyataz;|
| Active Comparator: Continuation<br>ATV 300 mg + RTV 100 mg + 2 NRTIs (TBD), ATV and RTV once daily, NRTIs (TBD) | Drug: Atazanavir + Ritonavir + 2 NRTIs<br>* Capsules, tablets, Oral, 48 weeks (after a 26-to-30-week induction phase with ATV 300 mg + RTV 100 mg + 2 NRTIs)<br>* Other names: Reyataz;|
| Other: Rescue<br>ATV 300 mg + RTV 100 mg + 2 NRTIs (TBD), ATV and RTV once daily, NRTIs (TBD) | Drug: Atazanavir + Ritonavir + 2 NRTIs<br>* Capsules, tablets, Oral, 48 weeks (after a 26-to-30-week induction phase with ATV 300 mg + RTV 100 mg + 2 NRTIs)<br>* Other names: Reyataz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL (c/mL) Through Week 48 of the Maintenance Phase | Participants were considered successes unless they experienced treatment failure, or had missing Week 48 HIV-1 RNA. Treatment failure: virologic rebound (ie, 2 consecutive on-treatment HIV-1 RNA ≥ 50 c/mL, or last HIV-1 RNA ≥ 50 c/mL followed by discontinuation), or discontinuation before Week 48. Denominator included all randomized participants. | From the end of Induction Phase (Week 26 to Week 30 of Induction Phase treatment) through Week 48 of Maintenance Phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA <400 c/mL Through Week 48 of the Maintenance Phase | Participants were considered successes unless they experienced treatment failure, or had missing Week 48 HIV-1 RNA. Treatment failure: virologic rebound (ie, 2 consecutive on-treatment HIV-1 RNA ≥ 400 c/mL, or last HIV-1 RNA ≥ 400 c/mL followed by discontinuation), or discontinuation before Week 48. Denominator included all randomized participants. | From the end of Induction Phase (Week 26 to Week 30 of Induction Phase treatment) through Week 48 of Maintenance Phase | 
| Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥50 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Treatment failure based on HIV-1 RNA ≥ 50 c/mL was defined as virologic rebound on or before Week 48 or discontinuation of study therapy before Week 48 for any reason. Time to treatment failure was analyzed using life tables. Measured Values shows the Kaplan-Meier cumulative proportion of participants without treatment failure up to the end of the respective interval. | Weeks 6-8, Weeks 14-16, Weeks 22-24, Weeks 30-32, Weeks 38-40, Weeks 46-48 | 
| Kaplan-Meier Cumulative Proportion for Treatment Failure (HIV-1 RNA ≥400 c/mL) at Different Time Points Through Week 48 of the Maintenance Phase | Treatment failure based on HIV-1 RNA ≥ 400 c/mL was defined as virologic rebound on or before Week 48 or discontinuation of study therapy before Week 48 for any reason. Time to treatment failure was analyzed using life tables. Measured Values shows the Kaplan-Meier cumulative proportion of participants without treatment failure up to the end of the respective interval. | Weeks 6-8, Weeks 14-16, Weeks 22-24, Weeks 30-32, Weeks 38-40, Weeks 46-48 | 
| Change From End of Induction Phase in CD4 Cell Count at Week 48 of Maintenance Phase | Change in CD4 Cell Count From End of Induction Phase at Week 48 of Maintenance Phase. Change=Week 48 maintenance Phase value - end of Induction Phase value; a decrease signifies worsening. | End of Induction Phase (Week 26 to Week 30 of Induction Phase treatment), Week 48 of Maintenance Phase | 
| Change From Baseline in CD4 Cell Count at Week 24 of Induction Phase | Change From Baseline in CD4 Count at Week 24 of Induction Phase. Change=Week 24 Induction Phase value - Baseline value; a decrease signifies worsening. | Baseline, Week 24 of Induction Phase | 
| Change From Baseline in CD4 Cell Count at Week 48 of Rescue Phase | Change From Baseline in CD4 Count at Week 48 of Rescue Phase. Change=Week 48 Rescue Phase value - Baseline value; a decrease signifies worsening. | Baseline, Week 48 of Rescue Phase | 
| Change From Baseline in HIV-1 RNA at Week 24 of the Induction Phase | Change From Baseline in HIV-1 RNA at Week 24 of the Induction Phase. Change=Week 24 Induction Phase value - Baseline value; a decrease signifies improvement. | Baseline, Week 24 of Induction Phase | 
| Change From Baseline in HIV-1 RNA at Week 48 of the Rescue Phase | Change From Baseline in HIV-1 RNA at Week 48 of the Rescue Phase. Change=Week 48 Rescue Phase value - Baseline value; a decrease signifies improvement. | \Baseline, Week 48 of Rescue Phase | 
| Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥50 c/mL) Through the End of Rescue Phase | Treatment outcome is based on the first reason of failure. These analyses were performed using HIV-1 RNA of 50 c/mL to define suppression and virologic rebound. | Through Week 48 of Rescue Phase. Measurements were included from the end of Induction Phase through the last dose of Rescue Phase study therapy plus 4 days. | 
| Treatment Outcomes Based on Viral Loads (HIV-1 RNA ≥400 c/mL) Through the End of Rescue Phase | Treatment outcome is based on the first reason of failure. These analyses were performed using HIV-1 RNA of 400 c/mL to define suppression and virologic rebound. | Baseline, Week 48 of Rescue Phase | 
| Time to Suppression (Confirmed HIV-1 RNA < 50 c/mL) During Treatment Phase | Description: Time to suppression was measured from the first dose of Induction Phase study therapy to the first of the 2 consecutive measurements < 50 c/mL. Time to suppression was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative number of treated participants without suppression up to the end of the respective interval. | Week 16-18, Week 24-26, Week 38-40, Week 64-66 | 
| Time to Suppression (Confirmed HIV-1 RNA < 400 c/mL) During Treatment Phase | Time to suppression was measured from the first dose of Induction Phase study therapy to the first of the 2 consecutive measurements <400 c/mL. Time to suppression was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative number of treated participants without suppression up to the end of the respective interval. | Week 16-18, Week 24-26, Week 30-32 | 
| Summary of Adverse Events During Induction Phase | Summary of Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. | Measurements are included through the earlier of the last dose of Induction Phase study therapy plus 30 days or the first dose of Maintenance/Rescue Phase therapy (ie, up until 26 to 31 weeks + 30 days). | 
| Summary of Adverse Events During Maintenance Phase | Summary of Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. | Measurements are included from the end of Induction Phase (26 to 30 weeks after first dose) through the last dose of Maintenance Phase study therapy plus 30 days. | 
| Summary of Adverse Events During Rescue Phase | Summary of Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. | Measurements are included from the end of Induction Phase (26 to 30 weeks after the first dose therapy) through the last dose of Rescue Phase study therapy plus 30 days. | 
| Percent Change From End of Induction Phase in Fasting Lipids at Week 48 of Maintenance Phase | Percent change in fasting lipids from end of Induction Phase to Week 48 of Maintenance Phase.Percent changes were calculated on the log scale and then back transformed to the original scale.Change=Week 48 maintenance Phase value - end of Induction Phase value; a decrease signifies worsening for HDL cholesterol and improvement for all other lipds. | Measurements were included from the end of Induction Phase (Week 26 to Week 30 of Induction therapy) through Week 48 of Maintenance Phase. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Naive, HIV-1 infected treatment naive patients