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

Phase 4

• Conditions: Allergic Cutaneous Vasculitis; Urticaria; Psoriasis; Sterile Pustulosis; Leprosy; Acne; Pneumocystis Pneumonia; Bullous Skin Diseases
• Interventions: Drug: Dapsone; Genetic: HLA-B*1301

• Registration Number: NCT02550080
• Lead Sponsor: Shandong Provincial Institute of Dermatology and Venereology

Brief Summary

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 Subjects who experience suspected DHS during the 6-week observation would be withdrawn from dapsone and undergo EPT patch testing 6 weeks later.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2015-08-20
• Study First Submitted QC: 2015-09-13
• Study First Posted: 2015-09-15
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-01
• Last Update Posted: 2017-03-03
• Primary Completion: 2018-12
• Study Completion: 2019-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 3130

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
The prospective genetic screening arm	HLA-B*1301	Prospective HLA-B\*1301 screen before administrated treatment included dapsone
The control arm	Dapsone	No HLA-B\*1301 screen before administrated treatment included dapsone
The prospective genetic screening arm	Dapsone	Prospective HLA-B\*1301 screen before administrated treatment included dapsone

Primary Outcome Measures

Name	Time	Method
Incidence of clinically-suspected DHS during the 6-week observation period	6 weeks	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).
Incidence of immunologically-confirmed DHS during the 6-week observation period	6 weeks	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).

Trial Locations

Locations (1)

Shandong Provincial Institute of Dermatology and Venereology; 🇨🇳 Jinan, Shandong, China