Rilpivirine in Virologically Suppressed Adolescents

Phase 2

• Conditions: HIV
• Interventions: Drug: Rilpivirine

• Registration Number: NCT03033368
• Lead Sponsor: Mahidol University

Brief Summary

To describe the immunologic and virologic outcomes (HIV RNA, CD4) following switching from EFV to RPV in virologically suppressed adolescents

Detailed Description

Study Procedures:

At screening, the informed consent process will be provided to participant, or participant legally acceptable representatives before any study procedure. Only adolescents who know their HIV status will be asked to give assent.

Twenty adolescents followed at HIV-NAT and the Department of Pediatrics, Faculty of Medicine, Chulalongkorn University will be asked to participate in the PK sub study. Participant who are enrolled in the PK substudy will be asked to take RPV in the morning after breakfast and then commence the PK evaluations after this witnessed dose. After the PK study at week 4, Participant will be followed with the other 80 adolescents until the end of the study. Participant will be asked to provide a small hair sample for RPV concentrations at weeks 4, 12, 24, and 48 after switching. This is an option therefore participant can refuse to provide their hair samples at any visits. HIV RNA levels will be performed at baseline, week 12, 24 and 48 visits. If the HIV-RNA at any visits is between \>50 copies/ml, the HIV-RNA test will be repeated within 4-8 weeks with adherence improvement counseling. At any visit, if HIV-RNA is ≥1000 copies/ml, genotypic resistance testing will be performed. Modification of treatment both for resistance and safety consideration will be subject to the site principal investigator's decision.

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2016-10-22
• Status Verified: 2017-01
• Study First Submitted QC: 2017-01-24
• Last Update Submitted: 2017-01-24
• Study First Posted: 2017-01-26
• Last Update Posted: 2017-01-26
• Primary Completion: 2017-06
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• HIV-infected adolescents aged 12-18 years;
• Body weight >25 kilograms;
• Currently treated with stable EFV-based HAART (EFV plus two nucleoside or nucleotide reverse transcriptase inhibitors [N(t)RTI]) for >3 months prior to enrollment;
• Plasma HIV RNA <50 copies/ml within the last 12 months;
• ALT <200 IU/L within the last 12 months;
• Caregivers give written informed consent and adolescents who know their HIV status (i.e., have been fully disclosed to) give assent

Exclusion Criteria

• Has evidence of NNRTI-associated resistance mutation(s) from previous genotypic resistance testing;
• Currently has PI(s) in the HAART regimen;
• Has currently active HIV-related infection(s), (The subject can be enrolled after the infection is under controlled);
• Has significant medical problem(s) that would compromise study results (in the site principal investigator's opinion);
• Pregnancy (postpartum women are allowed);
• Concomitant treatment with drugs known to effect the PK of RPV (carbamazepine, phenobarbital, phenytoin, rifampicin, rifabutin, omeprazole, esomeprazole, lansoprazole, erythromycin, clarithromycin, azithromycin, roxithromycin)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
opened label	Rilpivirine	Open-label, single-arm study, rilpivirine is the study drug

Primary Outcome Measures

Name	Time	Method
Proportion of adolescents with HIV-RNA <50 copies/ml at 48 weeks after switching.	48 weeks

Secondary Outcome Measures

Name	Time	Method
Change in fasting blood sugar after switching to RPV-containing regime	Baseline, week 24, and week 48	Measue fasting blood sugar (mg/dl)
Change in quality of life (QOL) score	Baseline, week 4 and week 24	Using PedsQLTM 4.0
Intensive PK parameter (Area under the plasma concentration-time curve; AUC0-24) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.	week 4	Measure area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24): unit; ng.h/ml
Change in neuropsychiatric test scores	Baseline and week 24	Using Trail Making Test and Coding subtest of WISC-III Wisconsin Card Sorting Test (WCST) Non-verbal part of Standard Progressive Matrices
Intensive PK parameter (maximum observed concentration of drug in plasma ;(Cmax) ) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.	week 4	Measue maximum observed concentration of drug in plasma (Cmax) : unit; ng/ml
Change in lipid profiles after switching to RPV-containing regimens	Baseline, week 24, and week 48	Measure cholesterol (mg/dl), LDL (mg/dl), HDL (mg/dl), triglyceride (mg/dl)
Intensive PK parameter (Minimum concentration of drug in plasma; (Ctrough)) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.	week 4	Measure minimum concentration of drug in plasma (Ctrough) : unit; ng/ml
Description of resistance mutations in the adolescents with RPV treatment failure	baseline, week 12, week 24 and week 48	At any visit, if HIV-RNA is ≥1000 copies/ml, genotypic resistance testing will be performed. Using HIV-1 Antiretroviral drug resistance ViriSeq HIV-1 genotyping