A Phase IV, Randomised, Multicentre, Double-blind, Study to Evaluate the Clinical Utility of Prospective Genetic Screening (HLA-B*5701) for Susceptibility to Abacavir Hypersensitivity
A Phase IV, Randomised, Multicentre, Double-blind, Study to Evaluate the Clinical Utility of Prospective Genetic Screening (HLA-B*5701) for Susceptibility to Abacavir Hypersensitivity
Study to evaluate the utility of prospective HLA-B*5701 screening on the incidence of abacavir hypersensitivity (ABC HSR) in 1800 previously ABC-naive adults with HIV-1 from Europe, Australia and other countries as applicable. The study has two (co-primary) objectives: i) to determine if screening for HLA-B*5701 prior to ABC-containing HAART results in a lower incidence of clinically-suspected HSR versus current standard of care (no genetic screening) and ii) to determine if screening for HLA-B*5701 prior to ABC-containing HAART, results in a significantly lower incidence of immunologically-confirmed HSR versus current standard of care (no genetic screening or patch testing). The study consists of up to a 28-day screening period, a randomised observation period (Day 1 through Week 6) and, for subjects experiencing a suspected ABC HSR and a subset of ABC-tolerant subjects, an epicutaneous patch test (EPT) assessment period. Eligible subjects will be randomised to one of two study arms: a Current Standard of Care Arm (no prospective genetic screening: Control) and a Genetic Screening Arm (prospective genetic screening). Subjects identified as HLA-B*5701 positive in the prospective Genetic Screening Arm will not receive ABC and will be excluded from further study. Subjects who experience suspected ABC HSR during the 6-week observation will be withdrawn from ABC-containing product and undergo EPT patch testing 6 weeks later.
Inclusion criteria:
Infected with documented HIV-1.
Subjects are Abacavir-naive (subjects can be antiretroviral therapy (ART)-naive or experienced).
All subjects must have a clinical need for treatment with Abacavir (ABC) or an ABC-containing product that precedes the decision to participate in the study.
If subjects are therapy naive they must meet the criteria for commencing HAART according to local guidelines.
ABC and ABC-containing products are not recommended during pregnancy. A female is eligible to enter and participate in the study if she is of:
Complete abstinence from intercourse from 4 weeks prior to administration of the ABC-containing compound, throughout the study, and for at least 4 weeks after discontinuation of ABC or ABC-containing product.
Double barrier method (e.g., male condom/spermicide, male condom/diaphragm, diaphragm/spermicide). Hormonal contraceptives will not be considered sufficient forms of contraception for this study.
Any intrauterine device with published data showing that the expected failure rate is <1% per year.
Sterilisation (male partner of female subject).
Exclusion criteria:
Torrette Di Ancona (an), The Marches 60020, Italy
Monte Funchal, 9054-535, Portugal
N.Novgorod, 603005, Russia
Baracaldo/Vizcaya, 48903, Spain
Marid, 28040, Spain
Woolwich, London, London SE18 4QH, United Kingdom
Dudley, Birmingham, DY1 4SE, United Kingdom
East Yorkshire, HU16 5JQ, United Kingdom
Farnworth, Bolton, BL4 0JR, United Kingdom
Plaistow, London, E13 8SL, United Kingdom