Pre-Exposure Prophylaxis Using TMC278LA
Pre-exposure prophylaxis (PrEP) is an experimental HIV-prevention strategy using antiretroviral (ARV) agents to protect HIV negative individuals from HIV infection.TMC278 is a new drug being developed for this type of HIV treatment. It is hoped that this drug may be used to help prevent HIV transmission in future. A 'long acting' formulation of TMC278 has been developed. Long acting means that the drug will be present in the blood for longer. It is this formulation of the drug that will be investigated in this study. Subjects will receive the drug by injection.
The purpose of this study is to investigate the safety of the drug and how well it is tolerated by the body. The study will look at the levels of the study drug in the subjects blood over the duration of the study.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||PrEP TMC278LA: Safety, Tolerability and Pharmacokinetics of TMC278LA in HIV Negative Volunteers|
- Local or systemic adverse events including local reactions to the IMP, all DAIDS (2004) grade ≥1 adverse events, serious adverse events (including laboratory abnormalities) and suspected unexpected serious adverse reactions (SUSARs) [ Time Frame: 217 ± 10 days ] [ Designated as safety issue: Yes ]
- Drug plasma pharmacokinetics following first i/m dose and at steady state [ Time Frame: 217 ± 10 days ] [ Designated as safety issue: No ]
- Male and female genital tract drug concentrations following first i/m dose and at steady state [ Time Frame: 217 ± 10 days ] [ Designated as safety issue: No ]
|Study Start Date:||March 2010|
|Study Completion Date:||May 2010|
|Primary Completion Date:||May 2010 (Final data collection date for primary outcome measure)|
Experimental: All subjects
TMC278LA 600mg injected intramuscularly (i/m)
TMC278LA 600mg injected intramuscularly (i/m)
Other Name: Rilpivirine
While for certain diseases, the use of medications by healthy people has been proven to function as prophylaxis, i.e. malaria, it is still unknown whether PrEP can help prevent HIV infection from exposure during sex or injection-drug use.
To address whether PrEP is safe and effective for use in humans, the traditional sequence of drug development steps should be followed as closely as possible.
TMC278 (rilpivirine) is a new investigational non nucleoside reverse transcriptase inhibitor (NNRTI) discovered and in development by Tibotec, a division of Johnson & Johnson. Data from clinical development (Phase IIB) suggest that TMC278 has a similar efficacy and better side-effect profile as compared to other, older, NNRTIs, such as efavirenz. Like TMC125 (etravirine), TMC278 is a diarylpyrimidine (DAPY - a class of molecule that resembles the pyrimidine nucleotides found in DNA, and which have shown potency in inhibiting the activity of HIV reverse transcriptase).
Tibotec is currently investigating TMC278 in two formulations: an oral formulation for HIV treatment and, in early phase, a long acting (LA) injectable formulation for HIV treatment. The latter has also potential application for HIV transmission prevention.
TMC278LA is an innovative drug formulation and its long apparent half life may allow administration of PrEP monthly rather than orally and daily, as for other ARV that are currently studied as PrEP agents.
Therefore, a phase I/II, open-label, prospective, single arm, pharmacokinetic clinical trial in 100 HIV negative subjects (50% of whom will have to be of self-identified African ancestry and 50% females, approximately) is to be conducted. The study will examine whether a monthly dose of TMC278LA not exceeding 600 mg i/m over a time period of approximately six months, with a loading regimen of the first two i/m injections separated by two weeks, is safe and well tolerated by HIV-negative subjects.
Investigation of drug pharmacokinetics in plasma and genital secretions will be also carried out in order to ensure optimal drug exposure during drug administration.
100 evaluable subjects will be enrolled, with approximately 50 of African ancestry, and 50 females. This will provide 50-subject-years of safety data in order to support a later large phase III global efficacy study.
|Royal Sussex County Hospital|
|Brighton, Sussex, United Kingdom, BN2 5BE|
|St Stephen's Centre|
|London, United Kingdom, SW10 9TH|
|St. Thomas's Hospital|
|London, United Kingdom, SE1 7EH|
|St. Mary's Hospital|
|London, United Kingdom, W2 1NY|
|Principal Investigator:||Marta Boffito, Dr||St Stephen's AIDS Trust (London)|
|Principal Investigator:||Akil Jackson, Dr||St Stephen's AIDS Trust (London)|
|Principal Investigator:||Martin Fisher, Dr||Royal Sussex County Hospital (Brighton)|
|Principal Investigator:||Alan Winston, Dr||St Mary's Hospital (London)|
|Principal Investigator:||Julie Fox, Dr||St. Thomas's Hospital (London)|