Safety and Efficacy Assessment of Two New Leprosy Skin Test Antigens: Randomized Double Blind Clinical Study

Autor: Patrick J. Brennan, Nathan A. Groathouse, Becky Rivoire, Stephen TerLouw
Rok vydání: 2014
Předmět:
Armadillos
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
Clinical Research Design
Guinea Pigs
Disease
Research and Analysis Methods
Microbiology
Pharmacotherapy
Drug Stability
Leprosy
Medicine and Health Sciences
medicine
Animals
Humans
Clinical Trials
Tissue Distribution
Mycobacterium leprae
Skin Tests
Antigens
Bacterial
Bacteriological Techniques
Lipoarabinomannan
biology
Transmission (medicine)
business.industry
lcsh:Public aspects of medicine
Public Health
Environmental and Occupational Health
Biology and Life Sciences
Neglected Diseases
Investigational New Drug
Tropical disease
lcsh:RA1-1270
Drugs
Investigational
medicine.disease
biology.organism_classification
3. Good health
Infectious Diseases
Research Design
Immunology
Clinical Medicine
business
Research Article
Biotechnology
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, Vol 8, Iss 5, p e2791 (2014)
ISSN: 1935-2735
DOI: 10.1371/journal.pntd.0002791
Popis: True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3–10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial.
Author Summary Despite reaching the global elimination target for leprosy, the need for a diagnostic tool to detect pre-symptomatic disease remains. Transmission has not been completely intercepted despite over 30 years of extensive curative treatment. With limited resources, two new leprosy skin test antigens, MLSA-LAM and MLCwA, suitable for human application were developed and manufactured in a local pilot plant. Requirements for manufacturing and clinical testing were met and an Investigational New Drug was established with the Food and Drug Administration to test both antigens in a phase I clinical trial for safety in a non-endemic region for leprosy and a phase II clinical trial for safety and efficacy in an endemic region for leprosy.
Databáze: OpenAIRE
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