Overview

Conditions acquired immune deficiency syndrome (aids), hiv infections
Treatments atv, drv, cobicistat, br
Phase phase 2/phase 3
Sponsor Gilead Sciences
Start date January 2014
End date December 2020
Trial size 100 participants
Trial identifier NCT02016924, 2013-001402-28, GS-US-216-0128

Summary

The primary objectives of this study are to evaluate the steady-state pharmacokinetics (PK) and confirm the dose of cobicistat-boosted atazanavir (ATV/co) or cobicistat-boosted darunavir (DRV/co) in HIV-1 infected antiretroviral treatment-experienced, virologically suppressed, pediatric participants between the ages of 3 months to < 18 years of age.

This study will also evaluate the safety, tolerability, and efficacy of ATV/co or DRV/co each co-administered with a background regimen (BR) through 48 weeks and during the 5 year long-term treatment.

There will be 2 parts to the study.

- Part A: Participants will be enrolled sequentially by age cohort to evaluate the steady state PK and confirm dose of ATV/co and DRV/co. Following screening, enrolled participants will continue their suppressive regimen of either ATV/r or DRV/r once-daily plus their BR. On Day 1, participants will discontinue ritonavir and initiate once daily cobicistat (COBI) to be taken with their ATV or DRV plus their BR. All participants enrolled in Part A will participate in an intensive PK evaluation of COBI and ATV or DRV on Day 10. Following completion of the intensive PK visit, participants will continue to receive COBI coadministered with DRV or ATV each with a BR and return for scheduled study visits.

- Part B: Participants will be enrolled to evaluate the safety, tolerability, and efficacy of the ATV/co or DRV/co regimen. For all cohorts in Part B, participants will be screened and initiated sequentially by each age cohort following confirmation of appropriate COBI exposure and PI exposures from the corresponding age cohort in Part A.

Recruiting in the following locations…

United States California, Colorado, District of Columbia, Florida, Georgia, Massachusetts, New York, Tennessee, and Texas
Other Countries Argentina and Thailand

Study Design

Allocation non-randomized
Endpoint classification pharmacokinetics study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants ages 12 to <18 years old will receive cobicistat 150 mg (2 x 75 mg or 1 x 150 mg) with either ATV or DRV plus BR.
atv Reyataz®
Capsules or powder administered once daily according to dosing recommendations per product monograph
drv Prezista®
Tablets or liquid oral suspension administered once daily according to dosing recommendations per product monograph
cobicistat GS-9350
Tablets or dispersible tablets as an oral suspension administered orally once daily with food
br
Background regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
(Experimental)
Participants ages 6 to <12 years old will receive cobicistat 150 mg (2 x 75 mg or 1 x 150 mg if ≥ 25 kg) or cobicistat 90 mg (if ≥ 15 kg and < 25 kg) with either ATV or DRV plus BR.
atv Reyataz®
Capsules or powder administered once daily according to dosing recommendations per product monograph
drv Prezista®
Tablets or liquid oral suspension administered once daily according to dosing recommendations per product monograph
cobicistat GS-9350
Tablets or dispersible tablets as an oral suspension administered orally once daily with food
br
Background regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
(Experimental)
Participants ages 3 to <6 years old will receive cobicistat (dose to be determined) with either ATV or DRV plus BR.
atv Reyataz®
Capsules or powder administered once daily according to dosing recommendations per product monograph
drv Prezista®
Tablets or liquid oral suspension administered once daily according to dosing recommendations per product monograph
cobicistat GS-9350
Tablets or dispersible tablets as an oral suspension administered orally once daily with food
br
Background regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
(Experimental)
Participants ages 3 months to <3 years old will receive cobicistat (dose to be determined) with ATV plus BR.
atv Reyataz®
Capsules or powder administered once daily according to dosing recommendations per product monograph
cobicistat GS-9350
Tablets or dispersible tablets as an oral suspension administered orally once daily with food
br
Background regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
(Experimental)
Participants ages 12 to <18 years old will receive cobicistat 150 mg (2 x 75 mg or 1 x 150 mg) with either ATV or DRV plus BR.
atv Reyataz®
Capsules or powder administered once daily according to dosing recommendations per product monograph
drv Prezista®
Tablets or liquid oral suspension administered once daily according to dosing recommendations per product monograph
cobicistat GS-9350
Tablets or dispersible tablets as an oral suspension administered orally once daily with food
br
Background regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
(Experimental)
Participants ages 6 to <12 years old will receive cobicistat 150 mg (2 x 75 mg or 1 x 150 mg if ≥ 25 kg) or cobicistat 90 mg (if ≥ 15 kg and < 25 kg) with either ATV or DRV plus BR.
atv Reyataz®
Capsules or powder administered once daily according to dosing recommendations per product monograph
drv Prezista®
Tablets or liquid oral suspension administered once daily according to dosing recommendations per product monograph
cobicistat GS-9350
Tablets or dispersible tablets as an oral suspension administered orally once daily with food
br
Background regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
(Experimental)
Participants ages 3 to <6 years old will receive cobicistat (dose to be determined) with either ATV or DRV plus BR.
atv Reyataz®
Capsules or powder administered once daily according to dosing recommendations per product monograph
drv Prezista®
Tablets or liquid oral suspension administered once daily according to dosing recommendations per product monograph
cobicistat GS-9350
Tablets or dispersible tablets as an oral suspension administered orally once daily with food
br
Background regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
(Experimental)
Participants ages 3 months to <3 years old will receive cobicistat (dose to be determined) with ATV plus BR.
atv Reyataz®
Capsules or powder administered once daily according to dosing recommendations per product monograph
cobicistat GS-9350
Tablets or dispersible tablets as an oral suspension administered orally once daily with food
br
Background regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.

Primary Outcomes

Measure
Pharmacokinetic (PK) Parameter: AUCtau of ATV and DRV
time frame: Predose and up to 12 hours postdose on Day 10
Incidence of Treatment-Emergent Adverse Events and Laboratory Abnormalities
time frame: Up to 6 years plus 30 days

Secondary Outcomes

Measure
PK Parameter: Ctau of ATV, DRV, and Cobicistat
time frame: Predose and up to 12 hours postdose on Day 10
PK Parameter: Cmax of ATV, DRV, and Cobicistat
time frame: Predose and up to 12 hours postdose on Day 10
PK Parameter: CL/F of ATV, DRV, and Cobicistat
time frame: Predose and up to 12 hours postdose on Day 10
PK Parameter: AUCtau of Cobicistat
time frame: Predose and up to 12 hours postdose on Day 10
PK Parameter: Vz/F of Cobicistat
time frame: Predose and up to 12 hours postdose on Day 10
Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL at Week 12
time frame: Week 12
Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL at Week 24
time frame: Week 24
Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL at Week 48
time frame: Week 48
Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL Every 12 Weeks After Week 48
time frame: Every 12 weeks after Week 48
Time to Pure Virologic Failure
time frame: Up to 6 years
Change from Baseline in log10 HIV-1 RNA (Copies/mL) at Week 24
time frame: Week 24
Change from Baseline in log10 HIV-1 RNA (Copies/mL) at Week 48
time frame: Week 48
Change from Baseline in log10 HIV-1 RNA (Copies/mL) Every 12 Weeks After Week 48
time frame: Every 12 weeks after Week 48
Change from Baseline in CD4+ Cell Count (Cells/µL) at Week 24
time frame: Week 24
Change from Baseline in CD4+ Cell Count (Cells/µL) at Week 48
time frame: Week 48
Change from Baseline in CD4+ Cell Count (Cells/µL) Every 12 Weeks After Week 48
time frame: Every 12 weeks after Week 48
Change from Baseline in CD4 Percentage at Week 24
time frame: Week 24
Change from Baseline in CD4 Percentage at Week 48
time frame: Week 48
Change from Baseline in CD4 Percentage Every 12 Weeks After Week 48
time frame: Every 12 weeks after Week 48
Acceptability and Palatability of Cobicistat
time frame: Up to Week 48

Eligibility Criteria

Male or female participants from 3 months up to 17 years old.

Key Inclusion Criteria: - HIV-1 infected treatment-experienced, virologically suppressed males and females aged 3 months to < 18 years at the Day 1 visit (according to requirements of enrolling Cohort) - Are able to provide written assent if they have the ability to read and write - Parent or legal guardian able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements - Body weight at screening ≥ 25 kg (Cohorts 1 and 2), 15 kg to < 25 kg (Cohort 2), or to be determined (Cohorts 3 and 4) dependent upon age cohort - Adequate renal function - Adequate hematologic function - Adequate hepatic function defined as - Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN) - Total bilirubin ≤ 1.5 mg/dL or a normal direct bilirubin - Negative serum pregnancy test - Individuals with evidence of suppressed viremia (< 50 copies/mL) at study entry - Stable antiretroviral regimen including 2 nucleoside reverse transcriptase inhibitors and either ritonavir-boosted atazanavir or ritonavir-boosted darunavir once or twice daily as per product label for a minimum of 3 months prior to the screening visit. Treatment-experienced pediatric individuals taking DRV/r must have no history of DRV resistance associated mutations. - Males and females 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 - Documented negative screening for active pulmonary tuberculosis (TB) per local standard of care within 6 months of a screening visit - Must be willing and able to comply with all study requirements - No opportunistic infection within 30 days of study entry (at Day -10) Key Exclusion Criteria: - Individuals with CD4+ cell counts at screening of less than 200 cells/mm^3 - An AIDS defining condition with onset within 30 days prior to screening - Life expectancy of less than 1 year - An ongoing serious infection requiring systemic antibiotic therapy at the time of screening. - Evidence of active pulmonary or extra-pulmonary tuberculosis disease: - Within 3 months of the screening visit for all individuals 6 months of age or older - At anytime for individuals younger than 6 months - Anticipated requirement for rifamycin treatment while participating in the study. Note: prophylactic isoniazid therapy for latent TB is allowed. - Active hepatitis C virus (HCV) infection. Note: individuals with positive HCV antibody and without detectable HCV RNA are permitted to enroll. - Positive Hepatitis B surface antigen or other evidence of active hepatitis B virus (HBV) infection. Note: individuals with positive HBV surface antibody and no evidence of active HBV infection are permitted to enroll. - Individuals with clinically significant abnormal ECGs - Have any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with treatment, assessment, or compliance with the protocol. - Individuals experiencing decompensated cirrhosis - A history of or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. - Pregnant or lactating females. - Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance. - Have history of significant drug sensitivity or drug allergy. - Known hypersensitivity to the study drug, the metabolites, or formulation excipients. - 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. - Individuals receiving ongoing therapy with any medication that is not to be taken with COBI or a component of the BR Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Additional Information

Official title A Phase 2/3, Multicenter, Open-label, Multicohort, Two-Part Study Evaluating Pharmacokinetics (PK), Safety, and Efficacy of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co), Administered With Background Regimen (BR) in HIV-1 Infected, Treatment-Experienced, Virologically Suppressed Pediatric Subjects
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by Gilead Sciences.