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

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

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 Subjects who experience suspected DHS during the 6-week observation would be withdrawn from dapsone and undergo EPT patch testing 6 weeks later.

Study Overview

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

• Study Type: Interventional
• Enrollment (Anticipated): 3130
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yonghu Sun, PhD; Phone Number: +86-531-87298870; Email: hongyue2519@hotmail.com
• Study Contact Backup: Name: Hong Liu, PhD; Phone Number: +86-531-87298870; Email: hongyue2519@hotmail.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250000
      • Recruiting
      • Shandong Provincial Institute of Dermatology and Venereology
      • Contact: Furen Zhang; Phone Number: +86-531-87298808; Email: zhangfuren@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shandong Provincial Institute of Dermatology and Venereology
• Collaborators: Shandong Provincial Hospital; Jinan Military General Hospital; Jinan Central Hospital; Shandong Jining No.1 People's Hospital; Liaocheng People's Hospital; Qingdao Hiser Medical Group; Dezhou People's Hospital; Shandong Qianfo Hospital; Dongying People's Hospital,Shandong; Jinan City Dermatology Hospital Prevention and Treatment; Linyi City Dermatology Hospital Prevention and Treatment; Jining City Dermatology Hospital Prevention and Treatment; Weifang City Dermatology Hospital Prevention and Treatment; Laiwu City Dermatology Hospital Prevention and Treatment; Rizhao City Dermatology Hospital Prevention and Treatment
• Investigators: Study Chair: Furen Zhang, Shandong Provincial Institute of Dermatology and Venereology

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): May 1, 2019

Study Registration Dates

• First Submitted: August 20, 2015
• First Submitted That Met QC Criteria: September 13, 2015
• First Posted (Estimate): September 15, 2015

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: March 1, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Pneumonia; Lung Diseases; Hypersensitivity, Immediate; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Skin Diseases, Vascular; Mycoses; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Immune Complex Diseases; Lung Diseases, Fungal; Pneumocystis Infections; Hypersensitivity; Skin Diseases; Vasculitis; Pneumonia, Pneumocystis; Urticaria; Leprosy; Skin Diseases, Vesiculobullous; Vasculitis, Leukocytoclastic, Cutaneous; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Dapsone
• Other Study ID Numbers: SDPIDV-DDS-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No