Clinical Utility Of Genetic Screening For HLA-B*5701, On Susceptibility To Abacavir Hypersensitivity

HIV Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00340080
• Other study ID #: CNA106030
• Secondary ID: PREDICT-1
• Status: Completed
• Phase: Phase 4
• First received: June 19, 2006
• Last updated: January 21, 2010
• Start date: April 2006

Study information

• Verified date: January 2010
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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 Subjects who experience suspected ABC HSR during the 6-week observation will be withdrawn from ABC-containing product and undergo EPT patch testing 6 weeks later.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1806
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Disease Susceptibility
• HIV Infection
• HIV Infections
• Hypersensitivity

Intervention

Drug:
• Abacavir

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Darlinghurst	New South Wales
Australia	GSK Investigational Site	Miami	Queensland
Austria	GSK Investigational Site	Graz
Austria	GSK Investigational Site	Innsbruck
Austria	GSK Investigational Site	Linz
Austria	GSK Investigational Site	Salzburg
Austria	GSK Investigational Site	Vienna
Belgium	GSK Investigational Site	Brugge
Belgium	GSK Investigational Site	Brussel
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Gent
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Liege
France	GSK Investigational Site	Aix En Provence
France	GSK Investigational Site	Amiens
France	GSK Investigational Site	Angers
France	GSK Investigational Site	Annecy
France	GSK Investigational Site	Avignon
France	GSK Investigational Site	Besançon
France	GSK Investigational Site	Bobigny Cedex
France	GSK Investigational Site	Bondy
France	GSK Investigational Site	Bordeaux
France	GSK Investigational Site	Bordeaux Cedex
France	GSK Investigational Site	Caen
France	GSK Investigational Site	Cannes
France	GSK Investigational Site	Clermont-Ferrand
France	GSK Investigational Site	Corbeil Essonnes Cedex
France	GSK Investigational Site	Créteil
France	GSK Investigational Site	Dijon
France	GSK Investigational Site	Fréjus
France	GSK Investigational Site	Grenoble
France	GSK Investigational Site	La Roche Sur Yon Cedex 9
France	GSK Investigational Site	La Rochelle
France	GSK Investigational Site	Le Kremlin Bicêtre Cedex
France	GSK Investigational Site	Levallois-Perret
France	GSK Investigational Site	Lyon Cedex 03
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Marseille Cedex 08
France	GSK Investigational Site	Metz
France	GSK Investigational Site	Montpellier Cedex 5
France	GSK Investigational Site	Mulhouse
France	GSK Investigational Site	Nantes
France	GSK Investigational Site	Nice
France	GSK Investigational Site	Nimes Cedex 9
France	GSK Investigational Site	Niort
France	GSK Investigational Site	Orléans
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Paris Cedex 10
France	GSK Investigational Site	Paris Cedex 13
France	GSK Investigational Site	Paris Cedex 14
France	GSK Investigational Site	Paris Cedex 20
France	GSK Investigational Site	Perpignan
France	GSK Investigational Site	Poitiers
France	GSK Investigational Site	Quimper
France	GSK Investigational Site	Reims
France	GSK Investigational Site	Rennes Cedex 09
France	GSK Investigational Site	Rouen
France	GSK Investigational Site	Saint Brieuc
France	GSK Investigational Site	Saint Denis Cedex 01
France	GSK Investigational Site	Saint-Etienne
France	GSK Investigational Site	Saint-Germain-en-Laye Cedex
France	GSK Investigational Site	Strasbourg
France	GSK Investigational Site	Toulouse
France	GSK Investigational Site	Tourcoing
France	GSK Investigational Site	Tours
France	GSK Investigational Site	Troyes
France	GSK Investigational Site	Valence
France	GSK Investigational Site	Valenciennes
France	GSK Investigational Site	Villejuif Cedex
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dortmund	Nordrhein-Westfalen
Germany	GSK Investigational Site	Erlangen	Bayern
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Freiburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Fuerth	Bayern
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Kiel	Schleswig-Holstein
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Germany	GSK Investigational Site	Osnabrueck	Niedersachsen
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Germany	GSK Investigational Site	Wuerzburg	Bayern
Ireland	GSK Investigational Site	Dublin
Israel	GSK Investigational Site	Kfar Saba
Israel	GSK Investigational Site	Ramat Gan
Israel	GSK Investigational Site	Rehovot
Israel	GSK Investigational Site	Tel-Aviv
Italy	GSK Investigational Site	Asti	Piemonte
Italy	GSK Investigational Site	Bari	Puglia
Italy	GSK Investigational Site	Bergamo	Lombardia
Italy	GSK Investigational Site	Bologna	Emilia-Romagna
Italy	GSK Investigational Site	Bologna	Emilia-Romagna
Italy	GSK Investigational Site	Bolzano	Trentino-Alto Adige
Italy	GSK Investigational Site	Brescia	Lombardia
Italy	GSK Investigational Site	Busto Arsizio (va)	Lombardia
Italy	GSK Investigational Site	Cagliari	Sardegna
Italy	GSK Investigational Site	Catania	Sicilia
Italy	GSK Investigational Site	Catanzaro	Calabria
Italy	GSK Investigational Site	Cuggiono (mi)	Lombardia
Italy	GSK Investigational Site	Ferrara	Emilia-Romagna
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Grosseto	Toscana
Italy	GSK Investigational Site	Latina	Lazio
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Padova	Veneto
Italy	GSK Investigational Site	Pallanza (Verbania)	Piemonte
Italy	GSK Investigational Site	Piacenza	Emilia-Romagna
Italy	GSK Investigational Site	Rimini	Emilia-Romagna
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Salerno	Campania
Italy	GSK Investigational Site	Sanremo (im)	Liguria
Italy	GSK Investigational Site	Sassari	Sardegna
Italy	GSK Investigational Site	Torino	Piemonte
Italy	GSK Investigational Site	Torrette Di Ancona (an)	Marche
Italy	GSK Investigational Site	Treviso	Veneto
Italy	GSK Investigational Site	Vicenza	Veneto
Latvia	GSK Investigational Site	Riga
Netherlands	GSK Investigational Site	Alkmaar
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Arnhem
Netherlands	GSK Investigational Site	Den Haag
Netherlands	GSK Investigational Site	Den Haag
Netherlands	GSK Investigational Site	Enschede
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Nijmegen
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Tilburg
Netherlands	GSK Investigational Site	Vlissingen
Netherlands	GSK Investigational Site	Zwolle
Norway	GSK Investigational Site	Fredrikstad
Norway	GSK Investigational Site	Oslo
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Chorzow
Poland	GSK Investigational Site	Szczecin
Poland	GSK Investigational Site	Warszawa
Portugal	GSK Investigational Site	Almada
Portugal	GSK Investigational Site	Amadora
Portugal	GSK Investigational Site	Aveiro
Portugal	GSK Investigational Site	Cascais
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Monte Funchal
Portugal	GSK Investigational Site	Ponta Delgada
Portugal	GSK Investigational Site	Porto
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Iasi
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Belgorod
Russian Federation	GSK Investigational Site	Krasnodar
Russian Federation	GSK Investigational Site	Lipetsk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Murmansk
Russian Federation	GSK Investigational Site	N.Novgorod
Russian Federation	GSK Investigational Site	Orel
Russian Federation	GSK Investigational Site	Perm
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Samara
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Smolensk
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Volgograd
Slovenia	GSK Investigational Site	Ljubljana
Spain	GSK Investigational Site	Alcala de Henares
Spain	GSK Investigational Site	Alicante
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Baracaldo/Vizcaya
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Bilbao
Spain	GSK Investigational Site	Calella
Spain	GSK Investigational Site	Córdoba
Spain	GSK Investigational Site	Elche (Alicante)
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	La Coruña
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Malaga
Spain	GSK Investigational Site	Marid
Spain	GSK Investigational Site	Mataro
Spain	GSK Investigational Site	Oviedo
Spain	GSK Investigational Site	Reus
Spain	GSK Investigational Site	San Sebastián
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Tarragona
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Vigo ( Pontevedra)
Spain	GSK Investigational Site	Vitoria
Switzerland	GSK Investigational Site	Basel
Switzerland	GSK Investigational Site	Bruderholz
Switzerland	GSK Investigational Site	La Chaux-de-Fonds
Switzerland	GSK Investigational Site	Lausanne
Switzerland	GSK Investigational Site	Lausanne
Switzerland	GSK Investigational Site	Lugano
Switzerland	GSK Investigational Site	St Gallen
Switzerland	GSK Investigational Site	Zurich
United Kingdom	GSK Investigational Site	Belfast
United Kingdom	GSK Investigational Site	Birmingham
United Kingdom	GSK Investigational Site	Coventry
United Kingdom	GSK Investigational Site	Derby	Derbyshire
United Kingdom	GSK Investigational Site	Dudley, Birmingham
United Kingdom	GSK Investigational Site	East Yorkshire
United Kingdom	GSK Investigational Site	Farnworth, Bolton
United Kingdom	GSK Investigational Site	Glasgow
United Kingdom	GSK Investigational Site	Gloucester
United Kingdom	GSK Investigational Site	Leicester
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester	Lancashire
United Kingdom	GSK Investigational Site	Middlesborough
United Kingdom	GSK Investigational Site	Nottingham	Nottinghamshire
United Kingdom	GSK Investigational Site	Plaistow, London
United Kingdom	GSK Investigational Site	Sheffield
United Kingdom	GSK Investigational Site	Stoke-on-Trent	Staffordshire
United Kingdom	GSK Investigational Site	Woolwich, London	London

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  France,  Germany,  Ireland,  Israel,  Italy,  Latvia,  Netherlands,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  Slovenia,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.