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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00340080
First received: June 19, 2006
Last updated: January 21, 2010
Last verified: January 2010
  Purpose

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 Subjects who experience suspected ABC HSR during the 6-week observation will be withdrawn from ABC-containing product and undergo EPT patch testing 6 weeks later.


Condition Intervention Phase
HIV Infection
Drug: Abacavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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.

Estimated Enrollment: 1806
Study Start Date: April 2006
Intervention Details:
    Drug: Abacavir
    Other Name: Abacavir
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00340080

  Show 254 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MB BS MRCP FFPM GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00340080     History of Changes
Other Study ID Numbers: CNA106030, PREDICT-1
Study First Received: June 19, 2006
Last Updated: January 21, 2010
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by GlaxoSmithKline:
Abacavir
Pharmacogenetics
hypersensitivity
HLA-B*5701

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Disease Susceptibility
HIV Infections
Hypersensitivity
Disease Attributes
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Pathologic Processes
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Abacavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014