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

Gilead Sciences

Status and phase

Terminated

Phase 3

Phase 2

Conditions

Acquired Immune Deficiency Syndrome (AIDS)

HIV Infections

Treatments

Drug: Background regimen

Drug: EVG

Study type

Interventional

Funder types

Industry

Identifiers

NCT01923311

2013-001969-16 (EudraCT Number)

GS-US-183-0160

Details and patient eligibility

About

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.

Enrollment

31 patients

Sex

All

Ages

4 weeks to 17 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

31 participants in 4 patient groups

Cohort 1 (12 to < 18 years of age)

Experimental group

Description:

Part A: No participants will be enrolled in Part A, as PK data is currently available for this age group. Part B: Participants will receive EVG plus a background regimen that includes a PI/r for up to 48 weeks. After Week 48, participants will be given the option to continue EVG therapy until the participant turns 18 and EVG is available for use in adults in the country in which the participant is enrolled, or the age appropriate EVG formulation becomes available for use in the country in which the participant is enrolled, or Gilead Sciences elects to terminate development of EVG in the applicable country.

Treatment:

Drug: EVG

Drug: Background regimen

Cohort 2 (6 to < 12 years of age)

Experimental group

Description:

Part A: Participants with HIV-1 RNA \< 50 copies/mL will receive EVG plus a background regimen that includes a PI/r for 10 days. Participants with HIV-1 RNA \> 1,000 copies/mL will receive EVG along with a newly constructed background regimen that includes a Pl/r for 48 weeks. Participants with HIV-1 RNA \> 1,000 copies/mL can continue after Week 48. Part B: Following confirmation of exposure to EVG and based on safety and PK data assessed in Part A, participants will receive EVG plus a background regimen that includes a PI/r for up to 48 weeks. Participants who complete the 48-week follow-up in both Part A and Part B will be given the option to continue EVG therapy until the participant turns 18 and EVG is available for use in adults in the country in which the participant is enrolled, or the age appropriate EVG formulation becomes available for use in the country in which the participant is enrolled, or Gilead Sciences elects to terminate development of EVG in the applicable country.

Treatment:

Drug: EVG

Drug: Background regimen

Cohort 3 (2 to < 6 years of age)

Experimental group

Description:

Part A: Participants with HIV-1 RNA \< 50 copies/mL will receive EVG plus a background regimen that includes a PI/r for 10 days. Part B: Following confirmation of exposure to EVG and based on safety and PK data assessed in Part A, participants will receive EVG plus a background regimen that includes a PI/r for up to 48 weeks. After Week 48, participants will be given the option to continue EVG therapy until the participant turns 18 and EVG is available for use in adults in the country in which the participant is enrolled, or the age appropriate EVG formulation becomes available for use in the country in which the participant is enrolled, or Gilead Sciences elects to terminate development of EVG in the applicable country.

Treatment:

Drug: EVG

Drug: Background regimen

Cohort 4 (4 weeks to < 2 years of age)

Experimental group

Description:

Treatment:

Drug: EVG

Drug: Background regimen

Trial documents