Safety, Tolerability, Drug Interactions, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive HIV-Infected Children Less Than 12 Years of Age

Active, not recruiting

• Conditions: HIV-1 Infection; MedDRA version: 16.1Level: LLTClassification code 10020192Term: HIV-1System Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2011-001680-44-Outside-EU/EEA
• Lead Sponsor: The National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01-24
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: Active
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Inclusion Criteria - Stage 1, Step 1 and Stage 2:
- A confirmed HIV-1 infection. More information on this criterion can be found in the protocol.
- Participant has never been treated with an HIV vaccine
- No evidence of prior ARV drug use with the exception of prior use of zidovudine (AZT) for up to 6 weeks to prevent mother-to-child transmission
- HIV-1 plasma viral load (VL) at screening greater than 500 HIV-1 RNA copies/mL but less than or equal to 100,000 HIV-1 RNA copies/mL (assayed by RNA polymerase chain reaction [PCR] standard specimen procedure) Note: Participants may be re-screened once only, if their baseline VL does not meet the entry criteria.
- In the judgment of the investigator, it is appropriate to initiate ARV therapy based on the participant's medical condition and taking into account guidelines for the treatment of HIV-1 infection in children
- Results from the genotypic resistance testing at screening demonstrate sensitivity to the selected NRTIs for the chosen background regimen
- Able to swallow whole tablets (Cohort 1 initial dose only)
- Female participants who are of child bearing potential and who are engaging in sexual activity that could lead to pregnancy, must use two adequate birth control methods while on study and for 4 weeks after stopping study drug. More information on this criterion can be found in the protocol.
- Children ages = 2 years to < 12 years

Inclusion Criteria - Stage 1, Step 2:
- Participants belonging to a cohort that failed Stage 1 Step 1 initial dose that meet the following criteria (as determined by the study team): Are able to have an adjustment in study drug dose (and the new dose would not exceed 25 mg) and appear to have room to stay within therapeutic range on the new dose

Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria - Stage 1, Step 1 and Stage 2:

- Having documented genotypic evidence of RPV resistance. More information on this criterion can be found in the protocol.
- Documented evidence of infection during breastfeeding by a mother taking NNRTI-based ART. If there are no data or no history available then the participant would be eligible as long as all other inclusion and exclusion criteria are fulfilled.
- Documented evidence of maternal NNRTI use during pregnancy. If there are no data or no history available then the participant would be eligible as long as all other inclusion and exclusion criteria are fulfilled.
- Previously documented HIV-2 infection in participant or participant's mother. If there are no data or no history available then the participant would be eligible as long as all other inclusion and exclusion criteria are fulfilled.
- Use of disallowed medication from 4 weeks prior to the entry visit or anticipated use of any disallowed medications
- Participant has used chronic systemic immunosuppressive agents within 30 days prior to entry or is anticipated to need chronic systemic immunosuppressive agents during the study. Short courses of systemic corticosteroids (e.g., prednisone or equivalent up to 2 mg/kg/day for 7 days) are permitted. Inhaled and intranasal steroids are permitted.
- Participant has any active AIDS-defining illness (Category C conditions according to the Centers for Disease Control and Prevention [CDC] revised Classification System for HIV Infection 1994), within 30 days prior to screening. Stable not currently active conditions that are not likely to interfere with safety assessments may be allowed with permission from the protocol team.
- Any active clinically significant disease or findings (other than HIV infection) during screening or medical history or physical examination that in the investigator's opinion, would compromise the outcome of the study
- Any confirmed Grade 3 or 4 laboratory toxicity according to the Division of AIDS (DAIDS) grading table at screening, except for: asymptomatic Grade 3 absolute neutrophil count decrease; asymptomatic Grade 3 platelet count decrease; asymptomatic Grade 3 total amylase, triglyceride, cholesterol elevation
- Participant has active tuberculosis and/or is being treated for tuberculosis at screening
- Participant has one or more of the following risk factors for ECG QTc prolongation:
?A confirmed prolongation of QT/QTc interval, (e.g., repeated demonstration of QTcF [Fridericia correction] interval greater than 450 ms in the screening ECG (i.e., retesting to reassess eligibility will be allowed once using an unscheduled visit during the screening period)
?Pathological Q-waves (defined as Q-wave greater than 40 ms or depth greater than 0.4-0.5 mV)
?Evidence of ventricular pre-excitation
?Electrocardiographic evidence of complete right or complete or incomplete left bundle branch block
?Evidence of second or third degree heart block
?Intraventricular conduction delay with QRS duration greater than 120 ms
?Bradycardia as defined by sinus rate less than 50 bpm
?Personal or family history of long QT syndrome
?Personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, with the exception of sinus arrhythmia
?Syncopal episodes
?Risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia)

- Participant's family is unlikely to adhere to the study procedures, keep appointments, or is planning to reloc

Study & Design

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