Evaluating the Safety and Tolerability of Etravirine in HIV-1 Infected Infants and Children

• Status: Completed
• Trial end date: 2020-08-26
• Target enrollment: 0
• Participant gender: All

Summary

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are widely used as part of combination antiretroviral therapy (ART) for infants and children, but NNRTI resistance is increasing, leading to treatment failure. This study tested the safety, tolerability, and dosing levels of etravirine (ETR), a new NNRTI.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Etravirine

Criteria

Inclusion Criteria:

• Confirmed HIV-1 infection as described in the protocol

• NOTE: Children who were born at or sooner than 37 weeks gestational age must be at least 12 weeks of age and at least 46 weeks post-conceptual age at study entry.

• HIV-1 RNA viral load greater than 1,000 copies/mL (within the previous 90 days prior to screening) and an HIV-1 RNA viral load greater than 1,000 copies/mL at screening

• Treatment-experienced children on a failing combination antiretroviral (ARV) regimen (containing at least three ARVs) for at least 8 weeks; OR, treatment-experienced children on a treatment interruption of at least 4 weeks with a history of virologic failure while on a combination ARV regimen (containing at least three ARVs)

• Ability to swallow etravirine (ETR) whole or dispersed in an appropriate liquid

• Parent or legal guardian able and willing to provide signed informed consent and to have the child followed at the clinic site

• Availability of sufficient active ARV drugs to create an optimized background regimen (OBR) consistent with protocol requirements

Exclusion Criteria:

• Evidence of phenotypic resistance to ETR at screening (phenotypic cutoffs of greater than 10 for loss of sensitivity for cohorts I, II, III)

• Known history of HIV-2 infection in child or child's mother

• Diagnosis of a new Centers for Disease Control (CDC) Stage C (per 1994 Revised Classification System for Human Immunodeficiency Virus Infection in Children Less than 13 Years of Age) criteria or opportunistic or bacterial infection diagnosed within 30 days prior to screening and not considered clinically stable

• Prior history of malignancy

• Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that in the investigator's opinion would place the child at an unacceptable risk of injury, render the child unable to meet the requirements of the protocol, compromise the outcome of this study, or lead to the child being ineligible for participation

• Current Grade 3 or higher of any of the following laboratory toxicities at screening:

neutrophil count, hemoglobin, platelets, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipase, or serum creatinine.

• Current or anticipated use of any disallowed medications (listed in the protocol)

• Child's family is unlikely to adhere to the study procedures or keep appointments or is planning to relocate to a non-IMPAACT study site during the study

• History of nonadherence with ARV medications that in the investigator's opinion could affect the ability of the child to comply with the protocol/procedures

• Child is currently participating, or has participated within the previous 30 days prior to screening, in a study with a compound or device that is not commercially available

• Grade 3 or higher QTc or PR interval prolongation from the electrocardiogram (ECG) at screening. More information on this criterion can be found in the protocol.