Two Part Study to Evaluate Pharmacokinetics, Safety, and Antiviral Activity of Elvitegravir Administered With a PI/r Background Regimen for ARV Treatment-Experienced Pediatric Participants

Phase 3TerminatedNCT01923311

Gilead Sciences31 enrolled

Overview

The 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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acquired Immune Deficiency Syndrome (AIDS)HIV Infections

Interventions

Eligibility

Sex: ALLMin age: 4 WeeksMax age: 17 Years

Medical Language ↔ Plain English

Key Inclusion 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 Exclusion Criteria: 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.

Outcomes

Primary Outcomes

Pharmacokinetic (PK) Parameter: AUCtau of EVG

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame: Predose and up to 12 hours postdose on Day 10

Pharmacokinetic (PK) Parameter: Cmax of EVG at Day 10

Cmax is defined as the maximum concentration of drug.

Time frame: Predose and up to 12 hours postdose on Day 10

Percentage of Participants Experiencing Treatment-emergent Adverse Events

Time frame: Baseline up to the last dose date plus 30 days (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years Screening HIV-1 RNA < 50 copies/mL)

Percentage of Participants Experiencing Laboratory Abnormalities

Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each subject. The criteria used to grade laboratory results were as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (life-threatening).

Secondary Outcomes

Pharmacokinetic (PK) Parameter: Ctau of EVG

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Time frame: Predose and up to 12 hours postdose on Day 10

Pharmacokinetic (PK) Parameter: CL/F of EVG

CL/F is defined as the apparent oral clearance following administration of the drug.

Time frame: Predose and up to 12 hours postdose on Day 10

Pharmacokinetic (PK) Parameter: Vz/F of EVG

Vz/F is defined as the apparent volume of distribution of the drug.

Time frame: Predose and up to 12 hours postdose on Day 10

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm

The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Time frame: Week 24

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm

The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Time frame: Week 48

Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm

The percentage of participants achieving HIV-1 RNA \< 400 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Time frame: Week 24

Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm

The percentage of participants achieving HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Time frame: Week 48

Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 24

Time frame: Baseline to Week 24

Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 48

Time frame: Baseline to Week 48

Change From Baseline in CD4 Cell Count at Week 24

Time frame: Baseline to Week 24

Change From Baseline in CD4 Cell Count at Week 48

Time frame: Baseline to Week 48

Change From Baseline in CD4 Percentage at Week 24

Time frame: Baseline to Week 24

Change From Baseline in CD4 Percentage at Week 48

Time frame: Baseline to Week 48

Tanner Stage Evaluation by Sex at Week 24

Tanner Stage (pubic hair and breasts for females; pubic hair and genitalia for males) at Week 24 visit was summarized using frequency count and percentage. Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics).

Time frame: Week 24

Tanner Stage Evaluation by Sex at Week 48

Tanner Stage (pubic hair and breasts for females; pubic hair and genitalia for males) at Week 48 visit was summarized using frequency count and percentage. Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics).

Time frame: Week 48

Age of First Menses

Age of first menses for female participants.

Time frame: Baseline through end of study (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years with Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years with Screening HIV-1 RNA < 50 copies/mL)

Palatability of Oral Suspension Formulation of EVG in Appropriate Age Group

Time frame: Up to Week 48

Adherence to EVG

Adherence was calculated as the number of pills taken divided by number of pills prescribed multiplied by 100.

Time frame: Baseline up to the last dose date (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years Screening HIV-1 RNA < 50 copies/mL)

Two Part Study to Evaluate Pharmacokinetics, Safety, and Antiviral Activity of Elvitegravir Administered With a PI/r Background Regimen for ARV Treatment-Experienced Pediatric Participants

Overview

Conditions

Interventions

Eligibility

Locations (11)

Outcomes

Primary Outcomes

Secondary Outcomes