A Phase 2/3 Multicenter, Open-Label, Multicohort, Two-Part Study Evaluating the Pharmacokinetics (PK), Safety, and Antiviral Activity of Elvitegravir (EVG) Administered With a Background-Regimen (BR) Containing a Ritonavir-Boosted Protease Inhibitor (PI/r) in HIV-1 Infected, Antiretroviral Treatment-Experienced Pediatric Subjects
Brief SummaryThe primary objectives of this study are to evaluate the safety, tolerability and steady-state PK and confirm the dose of EVG/r in HIV-1 infected, antiretroviral treatment-experienced children 4 weeks to <18 years of age. The study consists of 2 parts: Part A and Part B. Part A will enroll participants with suppressed viremia (HIV-1 RNA < 50 copies/mL) or failing a current antiretroviral (ARV) regimen (HIV-1 RNA > 1,000 copies/mL only for participants in Cohort 2, Part A) to evaluate the steady state PK and confirm the dose of EVG. Part B will enroll participants who are failing a current ARV regimen (HIV-1 RNA > 1,000 copies/mL) to evaluate the safety, tolerability, and antiviral activity of EVG. The study consists of 4 age cohorts with each cohort including 2 parts (Part A and Part B) with the exception of the adolescent age cohort (Cohort 1: 12 to < 18 years old) containing Part B only.
PhasePhase 2/3 - for trials that are a combination of phases 2 and 3.
Inclusion and Exclusion Criteria
- Individuals must meet all of the following inclusion criteria to be eligible for participation in this study. Individuals with screening results that do not meet eligibility criteria will not be allowed to rescreen.
- HIV-1 infected male and female individuals 4 weeks (gestational age of at least 44 weeks) to less than 18 years of age at Baseline.
- Individuals 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 5kg, 10.6kg, or 15kg 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)
- Total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin
- Negative serum pregnancy test
- Individuals with evidence of suppressed viremia
- Individuals failing a current antiretroviral regimen at study entry
- Male and female individuals of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse of reproductive potential throughout the study period and for 30 days following the last dose of study drug
- Must be willing and able to comply with all study requirements. Key
- Participants who meet any of the following exclusion criteria are not to be enrolled in this study.
- Individuals with CD4+ cell counts at Screening of less than 50, 75, or 200 cells/mm3 dependent on age cohort
- An AIDS defining condition with onset within 30 days prior to screening
- Life expectancy of less than 1 year
- For Individuals with HIV-1 RNA greater than 1,000 copies/mL at screening, prior treatment of any duration with an integrase strand transfer inhibitor.
- An ongoing serious infection requiring systemic antibiotic therapy at the time of screening.
- Evidence of active pulmonary or extra-pulmonary tuberculosis disease
- Anticipated requirement for rifamycin treatment while participating in the study.
- Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with Individual's 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 individual's 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 EVG or a component of the BR, including drugs not to be used with ritonavir Note: Other protocol defined Inclusion/ Exclusion criteria may apply.
- Jeffrey Goodman Clinic Los Angeles Gay and Lesbian Center, Los Angeles, California, 90027
- University of Colorado Denver, Aurora, Colorado, 80045
- University of Texas Health Science Center at Houston, Houston, Texas, 77030
- St. Jude Children's Research Hospital, Memphis, Tennessee, 38105
- Emory-Children's Center - Ponce Family and Youth Clinic, Atlanta, Georgia, 30308
- UO Clinica Pediatrica, Padua, 35128