Clinical Utility Of Genetic Screening For HLA-B*1301, On Susceptibility To Dapsone Hypersensitivity Syndrome

Study Overview
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Brief Summary
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This Study is to evaluate the utility of prospective HLA-B*1301 screening on the incidence of dapsone hypersensitivity syndrome (DHS) in 3130 previously Dapsone(DDS)-naive patients. Those patients include allergic cutaneous vasculitis, urticaria, psoriasis, acne, bullous skin diseases, sterile pustulosis, leprosy, pneumocystis pneumonia and any other patients who need dapsone administration. The study has two (co-primary) objectives: i) to determine if screening for HLA-B*1301 prior to DDS-containing treatment results in a lower incidence of clinically-suspected DHS versus current standard of care (no genetic screening) and ii) to determine if screening for HLA-B*1301 prior to DDS-containing treatment results in a significantly lower incidence of immunologically-confirmed DHS versus current standard of care (no genetic screening or patch testing). The study consists of up to a 5-day screening period, a randomised observation period (Day 1 through Week 6) and, for subjects experiencing a suspected DHS and a subset of DDS-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: Case). Subjects identified as HLA-B*1301 positive in the prospective Genetic Screening Arm will not receive dapsone and will be excluded from further study. Subjects who experience suspected DHS during the 6-week observation would be withdrawn from dapsone and undergo EPT patch testing 6 weeks later.

Official Title
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A Phase IV, Randomised, Multicentre, Double-blind, Study to Evaluate the Clinical Utility of Prospective Genetic Screening (HLA-B*1301) for Susceptibility to Dapsone Hypersensitivity Syndrome

Conditions
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Allergic Cutaneous Vasculitis, Urticaria, Psoriasis, Acne, Bullous Skin Diseases, Sterile Pustulosis, Leprosy, Pneumocystis Pneumonia

Intervention / Treatment
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* Drug: Dapsone
* Genetic: HLA-B*1301


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with cutaneous vasculitis, urticaria, psoriasis, acne, bullous skin diseases, sterile pustulosis, leprosy, pneumocystis pneumonia and any other patients who need dapsone administration. Subjects are dapsone-naive. All subjects must have a clinical need for treatment with dapsone that precedes the decision to participate in the study. All subjects are willing to complete the 6-weeks period clinical trial. All subjects are written informed consent. Exclusion Criteria: Has previously received Dapsone therapy. The subject or any of their healthcare providers is aware of the subjects HLA type. Has been diagnosed with Glucose-6-phosphate dehydrogenase deficiency or methemoglobin reductase deficiency Satisfies any contraindications or restrictions to Dapsone therapy as listed in the product labels. Current severe illness, including heart, 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 [alanine aminotransferase (ALT), glutamic oxaloacetic transaminase(ALT), et al). Pregnant women or women who are breastfeeding. Subject is, in the opinion of the Investigator, unable to complete the 6 week Observation period and the EPT assessments as required. A positive result for HLA-B*1301 in those subjects randomised to the genetic screening arm.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The prospective genetic screening arm<br>Prospective HLA-B*1301 screen before administrated treatment included dapsone | Drug: Dapsone<br>* For the HLA-B*1301 positive subjects, dapsone will not be administrated.<br>Genetic: HLA-B*1301<br>* The prospective genetic screening group will be tested before administrating dapsone<br>|
| Active Comparator: The control arm<br>No HLA-B*1301 screen before administrated treatment included dapsone | Drug: Dapsone<br>* For the HLA-B*1301 positive subjects, dapsone will not be administrated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinically-suspected DHS during the 6-week observation period | The primary outcome measure will be the total number of clinically suspected Dapsone induced hypersensitivity syndrome during the 6-week observation period in both the prospective-screening group and control group, as reported by the DHS incidence (DHS patients/ total participants). | 6 weeks | 
| Incidence of immunologically-confirmed DHS during the 6-week observation period | The primary outcome measure will be the total number of immunologically confirmed Dapsone induced hypersensitivity syndrome during the 6-week observation period in both the prospective-screening group and control group, as reported by the DHS incidence (DHS patients/ total participants). | 6 weeks |