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Pharmacokinetics, Safety, and Efficacy of Cobicistat-boosted Atazanavir or Cobicistat-boosted Darunavir in HIV-1 Infected, Treatment-Experienced, Virologically Suppressed Pediatric Subjects

Information source: Gilead Sciences
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acquired Immune Deficiency Syndrome (AIDS); HIV Infections

Intervention: ATV (Drug); DRV (Drug); Cobicistat (Drug); BR (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Gilead Sciences

Official(s) and/or principal investigator(s):
Martin Rhee, MD, Study Director, Affiliation: Gilead Sciences

Overall contact:
Gilead Study Team, Email: GSUS2160128@gilead.com

Summary

This study will 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 pediatric participants between the ages of 3 months to < 18 years of age. It 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 long-term treatment (total of 5 years). There will be 2 parts to the study.

- Part A: A minimum of 80 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 from Day - 10 through Day -1. All participants

enrolled in Part A will participate in an intensive PK evaluation of ATV or DRV on Day

- 1 and COBI and ATV or DRV on Day 10. On Day 1, participants will discontinue ritonavir

and initiate once daily cobicistat (COBI) to be taken with their ATV or DRV plus their BR. 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 through 5 years or as specified in Part B.

- Part B: A minimum of 20 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, additional 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. Overall, at least 100 participants in Parts A and B combined are planned to complete 5 years of the COBI containing treatment regimens.

Clinical Details

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Plasma concentration of drug over time (AUCtau) of ATV and DRV on Day 10

Incidence of treatment-emergent adverse events and laboratory abnormalities

Secondary outcome:

PK profiles of ATV and DRV

PK profile of cobicistat

Percentage of participants with plasma HIV-1 RNA < 50 copies/mL

The time to pure virologic failure

Change from baseline in log10 HIV-1 RNA (copies/mL)

Change from baseline in CD4+ cell count (cells/┬ÁL)

Acceptability (assessed by adherence) and palatability of cobicistat

Change from baseline in CD4 percentage

Change from baseline in CD4 percentage in participants < 5 years old

Eligibility

Minimum age: 3 Months. Maximum age: 17 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- HIV-1 infected treatment-experienced males and females aged 3 months to < 18 years at

the Day - 10 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 greater than 6. 25 kg, 10. 25 kg, or 15 kg dependent upon age

cohort

- Adequate renal function

- Adequate hematologic function

- Hepatic transaminases (AST and ALT) less than or equal to 5 x upper limit of normal

(ULN)

- For individuals on DRV/r, total bilirubin less than or equal to 1. 5 mg/dL and normal

direct bilirubin. For individuals on ATV/r, total bilirubin less than or equal to 3 mg/dL and 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)

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

Locations and Contacts

Gilead Study Team, Email: GSUS2160128@gilead.com

Pediatric Infectious Diseases Associate, Long Beach, California 90806, United States; Recruiting
Jagmohan Batra, MD, Principal Investigator

Children's Hospital Los Angeles, Los Angeles, California 90027, United States; Recruiting
Joseph Church, MD, Principal Investigator

Queen Savang Vadhana Memorial Hospital, Sriracha, Chonburi, Thailand; Not yet recruiting
Wicharn Luesomboon, Principal Investigator

Children's Hospital Colorado, Aurora, Colorado 80045, United States; Recruiting
Elizabeth McFarland, MD, Principal Investigator

Children's National Medical Center, Washington, District of Columbia 20852, United States; Recruiting
Natella Rakhmanina, Principal Investigator

University of South Florida Clinic at Children's Medical Services, Tampa, Florida 33620, United States; Recruiting
Carina Rodriguez, MD, Principal Investigator

Grady Health System, Atlanta, Georgia 30308, United States; Recruiting
Rana Chakraborty, MD, Principal Investigator

Srinagarind Hospital Khon Kaen University, Amphur Muang, Khon Kaen, Thailand; Recruiting
Pope Kosalaraksa, Principal Investigator

Siriraj Hospital Mahidol University, Bangkok, Krung Thep Maha Nakhon, Thailand; Recruiting
Kulkanya Chokephaibulkit, Principal Investigator

The HIV NAT Research Collaboration, Bangkok, Krung Thep Maha Nakhon, Thailand; Recruiting
Torsak Bunupuradah, Principal Investigator

Boston Medical Center, Boston, Massachusetts 02118, United States; Recruiting
Ellen R Cooper, MD, Principal Investigator

Bellevue Hospital, New York, New York 10016, United States; Recruiting
William Borkowsky, MD, Principal Investigator

SUNY Upstate Medical University, Syracuse, New York 13210, United States; Recruiting
Leonard Weiner, MD, Principal Investigator

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States; Recruiting
Aditya Gaur, MD, Principal Investigator

University of Texas Health Science Center of Houston, Houston, Texas 77030, United States; Recruiting
Gloria Heresi, MD, Principal Investigator

Additional Information

Starting date: January 2014
Last updated: August 20, 2015

Page last updated: August 23, 2015

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