A study to investigate the dose, safety and effectiveness of an experimental drug called elvitegravir for the treatment of HIV infection in children and adolescent patients. Patients must have previously received treatment for their HIV infection, and elvitegravir will be added to their current treatment which must include a ritonavir-boosted protease inhibitor.

• Conditions: Human Immunodeficiency Virus (HIV-1) Infections; MedDRA version: 17.1Level: LLTClassification code 10020192Term: HIV-1System Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2013-001969-16-Outside-EU/EEA
• Lead Sponsor: Gilead Sciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-02-18
• Last Update Posted: 23 February 2015

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 86

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.

4.2.1.HIV-1 infected male and female subjects 4 weeks (gestational age of at least 44 weeks) to < 18 years of age at the Baseline visit (according to Cohort).

4.2.2.Subjects are able to provide written assent if they have the ability to read and write.

4.2.3.Parent or legal guardian able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements.

4.2.4.Body weight at screening as follows:
•Cohort 2 – greater than 15 kg
•Cohort 3 – greater than 10.6 kg
•Cohort 4 – greater than 5 kg

4.2.5.Adequate renal function: Estimated Glomerular Filtration Rate (eGFR) = 90 mL/min/1.73m2 using the Schwartz Formula.

4.2.6.Adequate hematologic function defined as:
•Absolute neutrophil count > 500 cells/mm3 (Note: Subjects with chronic neutropenia, defined as having an ANC of < 500/mm3 documented at least twice within 6 months of screening, and in whom, according to the investigator, there is no evidence of active opportunistic or serious infection can enroll in the study contingent upon approval from the Gilead Medical Monitor.)
•Hemoglobin > 8.5 g/dL (9.5 g/dL for infants less than 35 days of age)
•Platelets > 50,000/mm3

4.2.7.Hepatic transaminases (AST and ALT) = 5 x upper limit of normal (ULN)

4.2.8.Total bilirubin = 1.5 mg/dL, or normal direct bilirubin

4.2.10.Negative serum ß-HCG pregnancy test for female subjects (of childbearing potential only, as defined in Section 7.8).

4.2.11.For subjects with evidence of suppressed viremia (Part A only):
•Plasma HIV-1 RNA concentration (at least 2 consecutive measurements) at an undetectable level according to the assay being used for at least 3 months prior to screening, and HIV-1 RNA <50 copies/mL (Roche COBAS TaqMan v2.0) at screening.
•Stable antiretroviral regimen including one of the following PI/r for at least 3 months prior to screening: lopinavir/r (Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or fosamprenavir/r. Subjects undergoing dose modifications to their antiretroviral regimen for growth or switching medication formulations are considered to be on a stable antiretroviral regimen.

4.2.12.For subjects failing a current antiretroviral regimen at study entry (Parts A and B):
•HIV-1 RNA >1,000 copies/mL at screening (Roche COBAS TaqMan v2.0).
•Prior treatment for HIV-1 infection, defined as 6 months of antiretroviral treatment experience (with the exception of Cohort 4 where less than 6 months of treatment experience is acceptable) and at least 1 documented resistance mutation as defined by current IAS-USA Guidelines. These resistance gene mutations must be documented in a historical genotype report(s), or in the genotype report at screening provided by Gilead Sciences.
•Stable antiretroviral regimen (or no antiretroviral regimen) for at least 30 days prior to screening. Subjects undergoing dose modifications to their antiretroviral regimen for growth or switching medication formulations are considered to be on a stable antiretroviral regimen.
•Screening genotype must show full sensitivity to EVG.
•Ability to construct a BR that must contain one of the following fully active PI/r: lopinavir/r (Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or fosamprenavir/r. (Fully active is defined by genotypic analysis.)
•Genotypic sensitivity score (GSS) of at least 2 (including the fully a

Exclusion Criteria

Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.

4.3.1.Subjects with the following CD4+ cell counts:
•For Cohorts 1 and 2: Screening CD4+ cell count < 50 cells/mm3
•For Cohort 3: Screening CD4+ cell count < 75 cells/mm3
•For Cohort 4: Screening CD4+ cell count < 200 cells/mm3

4.3.2.An acquired immunodeficiency syndrome (AIDS)-defining condition with onset within 30 days prior to screening (refer to Appendix 7)

4.3.3.Life expectancy of < 1 year

4.3.4.For subjects with HIV-1 RNA >1,000 copies/mL at screening, prior treatment of any duration with an integrase strand transfer inhibitor.

4.3.5.An ongoing serious infection requiring systemic antibiotic therapy at the time of screening.

4.3.6.Evidence of active pulmonary or extra-pulmonary tuberculosis disease:
•Within 3 months of the Screening visit for all subjects 6 months of age or older
•At any time for subjects younger than 6 months

4.3.7.Anticipated requirement for rifamycin treatment while participating in the study. Note: prophylactic isoniazid therapy for latent TB is allowed.

4.3.8.Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include uncontrolled renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment within 30 days prior to the study dosing.

4.3.9.Subjects experiencing decompensated cirrhosis (eg, ascites, encephalopathy)

4.3.10.A history of or ongoing malignancy other than cutaneous Kaposi’s sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Subjects with biopsy confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline and are not anticipated to require systemic therapy during the study.

4.3.11.Pregnant or lactating subjects.

4.3.12.Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance.

4.3.13.Have history of significant drug sensitivity or drug allergy.

4.3.14.Known hypersensitivity to the investigational medicinal product (IMP), the metabolites, or formulation excipients.

4.3.15.Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing.

4.3.16.Participation in any other clinical trial without prior approval from sponsor is prohibited while participating in this trial.

4.3.17.Subjects 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 (refer to prescribing information for drugs used as part of the BR); examples include the following-see protocol: (Administration of any of the following medications must be discontinued at least 30 days prior to the Baseline/Day 1 visit and for the duration of the study)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified