Pharmacogenomic Analysis of Samples From Subjects in Study RN1004-0082
Condition: Wound
Study type: Observational

Summary: 
      The objective of the study is to identify variations in subjects genetic makeup that
      segregate responders from non-responders in respect of response to Juvidex in the clinical
      trial RN1004-0082
    

Detailed description: 
      Injury to the skin results in the physical disruption of the normal cellular architecture and
      triggers wound healing: a process involving inflammation, cell proliferation and migration,
      cell recruitment, angiogenesis and extracellular matrix deposition. Growth factors and
      cytokines released from inflammatory cells dictate the function of those cells present within
      the wound. There is a clinical need for treatments that accelerate healing, as current
      therapies in this field are largely based on empirical treatments and are often ineffective
      or inadequate.Juvidex contains as an active ingredient mannose-6-phosphate (M-6-P), a
      naturally occurring low molecular weight monosaccharide. The proposed mechanism of action for
      Juvidex is antagonistic and involves inhibiting the activation of TGF-β1 and TGF-β2. Juvidex
      is being developed by Renovo as a therapeutic agent administered to accelerate the healing of
      acute wounds.

      Technological advances in genetics are providing scientists with the tools necessary to
      investigate the relationships between genetic variation and unmanipulated and drug-influenced
      wound healing outcomes such as the speed of healing. Determining the link between genetic
      variation and drug response (pharmacogenomics) is becoming an increasingly important part of
      drug development. For example, Iressa, which antagonises the tyrosine kinase activity of the
      epithelial growth factor receptor (EGFR) only works in people that have a specific variation
      (or polymorphism) in the DNA sequence of the EGFR gene. For Renovo, comparing the genetic
      make-up - (genotypes) - of subjects who respond well and those who respond poorly to a
      treatment, as well as those who naturally heal faster or whose wounds heal more slowly, may
      help to better define the most appropriate group of patients in which to target a given
      treatment. An additional benefit of exploring genotypes in well-defined patient populations
      will be to help to improve our understanding of the underlying biology of wound healing and
      provide new targets for drug discovery and development.

      Pharmacogenomics may ultimately lead to improved treatment of wound healing by using more
      effective drugs and safer prescribing regimes. In order to realise these benefits we need to
      be able to collect samples for genotyping analysis from the associated clinical trial. Renovo
      wishes to examine the DNA sequence of patients enrolled into its clinical studies in order to
      examine the variation in patients capacity to heal wounds. This study will analyse samples
      from subjects participating in clinical study RN1004-0082, a double blind, placebo controlled
      trial to investigate the efficacy and safety of two concentrations of Juvidex in accelerating
      the healing of split thickness skin graft donor sites using different dosing regimes.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This study will analyse samples from subjects participating in clinical study RN1004-0082,
        a double blind, placebo controlled trial to investigate the efficacy and safety of two
        concentrations of Juvidex in accelerating the healing of split thickness skin graft donor
        sites using different dosing regimes.
      
Biospecimen description: 
      Plasma retained until samples analysed then destroyed
    
Keywords: pharmacogenomics; polymorphisms; wound healing