Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Personalized Therapies in Inflammatory Complex Disease

Summary: Inflammatory diseases may display atypical features making such patients impossible to classify. Management of these cases in daily practice cannot rely on the results of clinical trials nor on guidelines. DNA and RNA mapping have become major tools to understand and sometimes direct the treatment strategy in oncology. This study aims to test whether a precise analysis of molecular pathways in inflammatory, non classified diseases, can constitute a predictive tool of therapeutic efficiency

Detailed description: This is a phase IIb study. The main objective of this study is to evaluate the efficacy of targeted treatments in patients displaying a non-classified, severe and resistant inflammatory disease. Targeted treatments for each patient will have been selected through an algorithm based on molecular analysis of specific altered inflammatory signaling pathway.
  Treatments consist in targeted therapies approved in other indications (Kineret®, Humira®, Stelara®, Cosentyx®, Roactemra® and Rituximab®) that will be given once selected using molecular analysis and decision making procedure by the Scientific committee.
  For each patient, one targeted treatment will be administered according to the SmPC procedure for a treatment period of 6 months.
  Primary efficacy endpoint:
  Response will be assessed at month 6 with a composite endpoint defined as improvement of at least 2 of the 3 following parameters:
  -  50% improvement of the systemic activity assessed by the clinician following a visual analog scale (0-10 mm),
  -  and/or 50% improvement of cutaneous activity assessed by the involved skin surface area,
  -  and/or 50% decrease or normalisation of biological markers of inflammation (either CRP, ESR or fibrin).
  An independent adjudication committee blinded to the treatment received, will review primary endpoint for all patients based on clinical files and standardized photographs, to validate the response.
  Other secondary criteria will be assessed. Overall, this study will require a molecular analysis done on patient's tissue, the final aim being to evaluate efficiency and tolerance of targeted treatments chosen in a personalized analysis when classification is impossible.

Eligibility: Inclusion Criteria:
  -  Patients (men or women) aged 18 years old and over
  -  Patients presenting inflammatory non classified disease targeting at least 2 organs involvement: skin, lymph nodes, hemopoietic system, joints, digestive tract. Skin involvement is mandatory in order to be able to compare involved and non-involved tissue
  -  Signed informed consent
  The disease should be considered as non-classified despite classical and adapted investigations and evaluation through expert committee meeting The disease alters significantly quality of life using SF36 assessment: score less than 30 The disease has been resistant to at least two prior lines of treatment
  Exclusion Criteria:
  -  Patients presenting disease which is not featured by lesional and healthy skin areas, easy to biopsy
  -  Patients refusing biopsies
  -  Pregnancy
  -  Breastfeeding
  -  Patients presenting disease needing urgent therapeutic measures
  -  Patients without health insurance or social security
  -  Participation in another trial

Relevance to patient case: not relevant