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

NCT ID: NCT01923311

Last Updated: 2018-08-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-26
• Study Completion Date: 2017-11-03

Brief Summary

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.

Conditions

Acquired Immune Deficiency Syndrome (AIDS); HIV Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 (12 to < 18 years of age)

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.

Group Type: EXPERIMENTAL

EVG

Intervention Type: DRUG

Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily

Background regimen

Intervention Type: DRUG

Background regimen may consist of the following ritonavir (RTV)-boosted PIs (PI/r): lopinavir/r (Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or fosamprenavir/r. For participants \< 2 months old, only lopinavir/r is allowed. Use of additional antiretrovirals in background therapy may be allowed.

Cohort 2 (6 to < 12 years of age)

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.

Group Type: EXPERIMENTAL

EVG

Intervention Type: DRUG

Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily

Background regimen

Intervention Type: DRUG

Background regimen may consist of the following ritonavir (RTV)-boosted PIs (PI/r): lopinavir/r (Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or fosamprenavir/r. For participants \< 2 months old, only lopinavir/r is allowed. Use of additional antiretrovirals in background therapy may be allowed.

Cohort 3 (2 to < 6 years of age)

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.

Group Type: EXPERIMENTAL

EVG

Intervention Type: DRUG

Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily

Background regimen

Intervention Type: DRUG

Background regimen may consist of the following ritonavir (RTV)-boosted PIs (PI/r): lopinavir/r (Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or fosamprenavir/r. For participants \< 2 months old, only lopinavir/r is allowed. Use of additional antiretrovirals in background therapy may be allowed.

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

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.

Group Type: EXPERIMENTAL

EVG

Intervention Type: DRUG

Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily

Background regimen

Intervention Type: DRUG

Background regimen may consist of the following ritonavir (RTV)-boosted PIs (PI/r): lopinavir/r (Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or fosamprenavir/r. For participants \< 2 months old, only lopinavir/r is allowed. Use of additional antiretrovirals in background therapy may be allowed.

Interventions

EVG

Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily

Intervention Type: DRUG

Background regimen

Background regimen may consist of the following ritonavir (RTV)-boosted PIs (PI/r): lopinavir/r (Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or fosamprenavir/r. For participants \< 2 months old, only lopinavir/r is allowed. Use of additional antiretrovirals in background therapy may be allowed.

Intervention Type: DRUG

Other Intervention Names

Vitekta®

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 4 Weeks
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

University of Colorado Denver

Aurora, Colorado, United States

Duke University Medical Center

Durham, North Carolina, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Be Part Yoluntu Centre

Cape Town, , South Africa

Rahima Moosa Mother and Child Hopsital

Johannesburg, , South Africa

Hospital Universitario De Getafe

Getafe, Madrid, Spain

Hospital 12 de Octubre

Madrid, , Spain

Thai Red Cross AIDS Research Centre (HIV-NAT)

Bangkok, , Thailand

Siriraj Hospital

Bangkok, , Thailand

Joint Clinical Research Centre

Kampala, , Uganda

Countries

United States; Italy; South Africa; Spain; Thailand; Uganda

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-001969-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-183-0160

Identifier Type: -

Identifier Source: org_study_id