Clinical trial NCT00340080: Clinical Utility Of Genetic Screening For HLA-B*5701, On Susceptibility To Abacavir Hypersensitivity
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infection
Keywords: Abacavir
Pharmacogenetics
hypersensitivity
HLA-B*5701
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-06-21
Enrollment: 1806
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 Subjects who experience suspected ABC HSR during the 6-week observation will be withdrawn from ABC-containing product and undergo EPT patch testing 6 weeks later.


Eligibility criteria: 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:

  1. Non-child-bearing potential: women who are surgically sterile or post-menopausal, the latter indicated by history of no menses for a minimum of 1 year from the date of the screening visit.
  2. Child-bearing potential: women who provide a negative pregnancy test (beta-human chorionic gonadotrophin; beta-HCG) at Screening and who agree to one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the approved product label and the instructions of a physician, during the study period and through epicutaneous patch testing where appropriate):
* 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:

* Has previously received ABC-containing therapy.
* Satisfies any contraindications or restrictions to ABC therapy as listed in the product labels. Treatment with ABC must be in line with the recommendations of the product label.
* The subject or any of their healthcare providers is aware of the subjects HLA type.
* Has undergone an allogeneic bone marrow transplant.
* Has an active or acute CDC Clinical Category C event at screening. Treatment for the acute event must have been completed at least 30 days prior to Screening.
* Current severe illness, including liver and renal failure, major organ allograft, malignancy requiring parenteral chemotherapy that can not be discontinued for the duration of the trial, or any other conditions which, in the opinion of the Investigator, would make the patient unsuitable for the study.
* Any laboratory abnormality at Screening which, in the opinion of the Investigator, should preclude the subject's participation in the study.
* Pregnant women or women who are breastfeeding.
* Any immunisation within 30 days prior to Day 1.
* Subject is, in the opinion of the Investigator, unable to complete the 6 week Observation period and the EPT assessments as required.
* Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to Screening, or has an anticipated need for these agents within the study period.
* Subject is enrolled in one or more investigational drug/vaccine protocols.
* In France, an eligible subject is neither affiliated with nor a beneficiary of a social security category.
* A subject will not be eligible for progression to Baseline (Day 1) if any of the following criteria apply:
* A positive result for HLA-B\*5701 in those subjects randomised to the genetic screening arm.

Primary outcomes:
measure: Incidence of clinically-suspected ABC HSR during the 6-week observation period. Incidence of immunologically-confirmed ABC HSR. The clinical diagnosis of which occurs over the 6-week observation period.
Secondary outcomes:
measure: Incidence of clinically-suspected ABC HSR in Caucasians and in different ethnic sub-groups. Sensitivity and specificity, positive and negative predictive value of genetic screening for HLA-B*5701 for susceptibility of HSR.
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Miami
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Graz
country: Austria
facility: GSK Investigational Site
city: Innsbruck
country: Austria
facility: GSK Investigational Site
city: Linz
country: Austria
facility: GSK Investigational Site
city: Salzburg
country: Austria
facility: GSK Investigational Site
city: Vienna
country: Austria
facility: GSK Investigational Site
city: Brugge
country: Belgium
facility: GSK Investigational Site
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Brussel
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Liege
country: Belgium
facility: GSK Investigational Site
city: Aix En Provence
country: France
facility: GSK Investigational Site
city: Amiens
country: France
facility: GSK Investigational Site
city: Angers
country: France
facility: GSK Investigational Site
city: Annecy
country: France
facility: GSK Investigational Site
city: Avignon
country: France
facility: GSK Investigational Site
city: Besançon
country: France
facility: GSK Investigational Site
city: Bobigny Cedex
country: France
facility: GSK Investigational Site
city: Bondy
country: France
facility: GSK Investigational Site
city: Bordeaux Cedex
country: France
facility: GSK Investigational Site
city: Bordeaux
country: France
facility: GSK Investigational Site
city: Caen
country: France
facility: GSK Investigational Site
city: Cannes
country: France
facility: GSK Investigational Site
city: Clermont-Ferrand
country: France
facility: GSK Investigational Site
city: Corbeil Essonnes Cedex
country: France
facility: GSK Investigational Site
city: Créteil
country: France
facility: GSK Investigational Site
city: Dijon
country: France
facility: GSK Investigational Site
city: Fréjus
country: France
facility: GSK Investigational Site
city: Grenoble
country: France
facility: GSK Investigational Site
city: La Roche Sur Yon Cedex 9
country: France
facility: GSK Investigational Site
city: La Rochelle
country: France
facility: GSK Investigational Site
city: Le Kremlin Bicêtre Cedex
country: France
facility: GSK Investigational Site
city: Levallois-Perret
country: France
facility: GSK Investigational Site
city: Lyon Cedex 03
country: France
facility: GSK Investigational Site
city: Marseille Cedex 08
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Metz
country: France
facility: GSK Investigational Site
city: Montpellier Cedex 5
country: France
facility: GSK Investigational Site
city: Mulhouse
country: France
facility: GSK Investigational Site
city: Nantes
country: France
facility: GSK Investigational Site
city: Nice
country: France
facility: GSK Investigational Site
city: Nimes Cedex 9
country: France
facility: GSK Investigational Site
city: Niort
country: France
facility: GSK Investigational Site
city: Orléans
country: France
facility: GSK Investigational Site
city: Paris Cedex 10
country: France
facility: GSK Investigational Site
city: Paris Cedex 13
country: France
facility: GSK Investigational Site
city: Paris Cedex 14
country: France
facility: GSK Investigational Site
city: Paris Cedex 20
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Perpignan
country: France
facility: GSK Investigational Site
city: Poitiers
country: France
facility: GSK Investigational Site
city: Quimper
country: France
facility: GSK Investigational Site
city: Reims
country: France
facility: GSK Investigational Site
city: Rennes Cedex 09
country: France
facility: GSK Investigational Site
city: Rouen
country: France
facility: GSK Investigational Site
city: Saint Brieuc
country: France
facility: GSK Investigational Site
city: Saint Denis Cedex 01
country: France
facility: GSK Investigational Site
city: Saint-Etienne
country: France
facility: GSK Investigational Site
city: Saint-Germain-en-Laye Cedex
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Toulouse
country: France
facility: GSK Investigational Site
city: Tourcoing
country: France
facility: GSK Investigational Site
city: Tours
country: France
facility: GSK Investigational Site
city: Troyes
country: France
facility: GSK Investigational Site
city: Valence
country: France
facility: GSK Investigational Site
city: Valenciennes
country: France
facility: GSK Investigational Site
city: Villejuif Cedex
country: France
facility: GSK Investigational Site
city: Freiburg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Stuttgart
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Erlangen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Fuerth
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Osnabrueck
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Dortmund
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Kiel
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Kfar Saba
country: Israel
facility: GSK Investigational Site
city: Ramat Gan
country: Israel
facility: GSK Investigational Site
city: Rehovot
country: Israel
facility: GSK Investigational Site
city: Tel-Aviv
country: Israel
facility: GSK Investigational Site
city: Catanzaro
country: Italy
facility: GSK Investigational Site
state: Calabria
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: Salerno
country: Italy
facility: GSK Investigational Site
state: Campania
city: Bologna
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Bologna
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Ferrara
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Piacenza
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Rimini
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Latina
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Sanremo (im)
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Bergamo
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Brescia
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Busto Arsizio (va)
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Cuggiono (mi)
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Torrette Di Ancona (an)
country: Italy
facility: GSK Investigational Site
state: Marche
city: Asti
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Pallanza (Verbania)
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Bari
country: Italy
facility: GSK Investigational Site
state: Puglia
city: Cagliari
country: Italy
facility: GSK Investigational Site
state: Sardegna
city: Sassari
country: Italy
facility: GSK Investigational Site
state: Sardegna
city: Catania
country: Italy
facility: GSK Investigational Site
state: Sicilia
city: Grosseto
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Bolzano
country: Italy
facility: GSK Investigational Site
state: Trentino-Alto Adige
city: Padova
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Treviso
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Vicenza
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Riga
country: Latvia
facility: GSK Investigational Site
city: Alkmaar
country: Netherlands
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Arnhem
country: Netherlands
facility: GSK Investigational Site
city: Den Haag
country: Netherlands
facility: GSK Investigational Site
city: Den Haag
country: Netherlands
facility: GSK Investigational Site
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Groningen
country: Netherlands
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Tilburg
country: Netherlands
facility: GSK Investigational Site
city: Vlissingen
country: Netherlands
facility: GSK Investigational Site
city: Zwolle
country: Netherlands
facility: GSK Investigational Site
city: Fredrikstad
country: Norway
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Chorzow
country: Poland
facility: GSK Investigational Site
city: Szczecin
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Almada
country: Portugal
facility: GSK Investigational Site
city: Amadora
country: Portugal
facility: GSK Investigational Site
city: Aveiro
country: Portugal
facility: GSK Investigational Site
city: Cascais
country: Portugal
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Monte Funchal
country: Portugal
facility: GSK Investigational Site
city: Ponta Delgada
country: Portugal
facility: GSK Investigational Site
city: Porto
country: Portugal
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: Barnaul
country: Russian Federation
facility: GSK Investigational Site
city: Belgorod
country: Russian Federation
facility: GSK Investigational Site
city: Krasnodar
country: Russian Federation
facility: GSK Investigational Site
city: Lipetsk
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Murmansk
country: Russian Federation
facility: GSK Investigational Site
city: N.Novgorod
country: Russian Federation
facility: GSK Investigational Site
city: Orel
country: Russian Federation
facility: GSK Investigational Site
city: Perm
country: Russian Federation
facility: GSK Investigational Site
city: Ryazan
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Samara
country: Russian Federation
facility: GSK Investigational Site
city: Saratov
country: Russian Federation
facility: GSK Investigational Site
city: Smolensk
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Volgograd
country: Russian Federation
facility: GSK Investigational Site
city: Ljubljana
country: Slovenia
facility: GSK Investigational Site
city: Alcala de Henares
country: Spain
facility: GSK Investigational Site
city: Alicante
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Baracaldo/Vizcaya
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Bilbao
country: Spain
facility: GSK Investigational Site
city: Calella
country: Spain
facility: GSK Investigational Site
city: Córdoba
country: Spain
facility: GSK Investigational Site
city: Elche (Alicante)
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: La Coruña
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: Marid
country: Spain
facility: GSK Investigational Site
city: Mataro
country: Spain
facility: GSK Investigational Site
city: Oviedo
country: Spain
facility: GSK Investigational Site
city: Reus
country: Spain
facility: GSK Investigational Site
city: San Sebastián
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Tarragona
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Vigo ( Pontevedra)
country: Spain
facility: GSK Investigational Site
city: Vitoria
country: Spain
facility: GSK Investigational Site
city: Basel
country: Switzerland
facility: GSK Investigational Site
city: Bruderholz
country: Switzerland
facility: GSK Investigational Site
city: La Chaux-de-Fonds
country: Switzerland
facility: GSK Investigational Site
city: Lausanne
country: Switzerland
facility: GSK Investigational Site
city: Lausanne
country: Switzerland
facility: GSK Investigational Site
city: Lugano
country: Switzerland
facility: GSK Investigational Site
city: St Gallen
country: Switzerland
facility: GSK Investigational Site
city: Zurich
country: Switzerland
facility: GSK Investigational Site
city: Derby
country: United Kingdom
facility: GSK Investigational Site
state: Derbyshire
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
city: Woolwich, London
country: United Kingdom
facility: GSK Investigational Site
state: London
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
state: Nottinghamshire
city: Stoke-on-Trent
country: United Kingdom
facility: GSK Investigational Site
state: Staffordshire
city: Belfast
country: United Kingdom
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Coventry
country: United Kingdom
facility: GSK Investigational Site
city: Dudley, Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: East Yorkshire
country: United Kingdom
facility: GSK Investigational Site
city: Farnworth, Bolton
country: United Kingdom
facility: GSK Investigational Site
city: Glasgow
country: United Kingdom
facility: GSK Investigational Site
city: Gloucester
country: United Kingdom
facility: GSK Investigational Site
city: Leicester
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Middlesborough
country: United Kingdom
facility: GSK Investigational Site
city: Plaistow, London
country: United Kingdom
facility: GSK Investigational Site
city: Sheffield
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials, MB BS MRCP FFPM
role: STUDY_DIRECTOR
References:
citation: Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, Jagel-Guedes E, Rugina S, Kozyrev O, Cid JF, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, Thorborn D, Benbow A; PREDICT-1 Study Team. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008 Feb 7;358(6):568-79. doi: 10.1056/NEJMoa0706135.