Clinical trial NCT02550080: Clinical Utility Of Genetic Screening For HLA-B*1301, On Susceptibility To Dapsone Hypersensitivity Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Allergic Cutaneous Vasculitis
Urticaria
Psoriasis
Acne
Bullous Skin Diseases
Sterile Pustulosis
Leprosy
Pneumocystis Pneumonia
Lead sponsor: Shandong Provincial Institute of Dermatology and Venereology
Sponsor class: OTHER
Collaborators: name: Shandong Provincial Hospital
name: Jinan Central Hospital
name: Shandong Qianfo Hospital
name: Jinan Military General Hospital
name: Qingdao Hiser Medical Group
name: Liaocheng People's Hospital
name: Dongying People's Hospital,Shandong
name: Jining First People's Hospital
name: Dezhou People's Hospital
name: Jinan City Dermatology Hospital Prevention and Treatment
name: Linyi City Dermatology Hospital Prevention and Treatment
name: Jining City Dermatology Hospital Prevention and Treatment
name: Weifang City Dermatology Hospital Prevention and Treatment
name: Laiwu City Dermatology Hospital Prevention and Treatment
name: Rizhao City Dermatology Hospital Prevention and Treatment
First posted: 2015-09-15
Enrollment: 3130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of clinically-suspected DHS during the 6-week observation period
timeFrame: 6 weeks
measure: Incidence of immunologically-confirmed DHS during the 6-week observation period
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Provincial Institute of Dermatology and Venereology
state: Shandong
Study officials:
affiliation: Shandong Provincial Institute of Dermatology and Venereology
name: Furen Zhang
role: STUDY_CHAIR
References: