An Exploratory Study of Genetic and Clinical Factors for Serious Skin Reactions Among Users of Eslicarbazepine Acetate

Study Overview
=================
Brief Summary
-----------------
The reason for this study is to understand if people with certain genes are predisposed to develop severe skin reactions after they are administered Eslicarbazepine Acetate. Currently there is no information that suggests that certain individuals who use Eslicarbazepine Acetate are predisposed to develop severe skin reactions. However, previous research has shown that seizure medicines like carbamazepine (Tegretol®) and oxcarbazepine (Trileptal®, Oxtellar XR®) are more likely to cause severe drug related skin reactions in some people of Asian ancestry who have specific genes. These are genes found in an area of chromosomes called the Major Histocompatibility Complex. This association is called a genetic risk factor. The study objective is to compare information that is obtained from individuals with a history of seizure disorders who develop severe skin reactions while using Eslicarbazepine Acetate to a group of patients who also have a history of seizure disorders and do not have a history of a severe skin reaction after using Eslicarbazepine Acetate.

Detailed Description
-----------------
This study is a genetic case-control study conducted in the United States. In case-control studies, cases with a condition of interest (in this case, individuals with SCAR [severe cutaneous adverse reactions] after initiating ESL); and controls, individuals known to not have the condition of interest (in this case ESL users without SCAR), are identified. Cases will be individuals with documented definite or probable Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) or symptom onset consistent with one of these conditions within the first 4 months of using ESL (including up to 14 days after discontinuing ESL), ascertained through PPD Pharmacovigilance (PVG) (Sponsor CRO). Controls will be individuals who have used ESL for at least 6 weeks but did not develop any SCAR and will be matched by genetic ancestry classification in a ratio of up to 10 controls per case. Controls will be collected prospectively, so that a pool of ESL-tolerant patients will be identified independently of the collection of cases. Controls will be selected from among: Ongoing subjects in clinical studies of ESL; and Patients prescribed ESL who may be asked to participate by neurologists at high-prescribing practices with high ethnic diversity. Blood or saliva samples for genotyping ancestry markers (for matching controls to cases) and sequencing the HLA regions will be collected from cases and control subjects after they have provided consent for participation in a genetic study. In addition, a blood sample will be requested from subjects to assess the relationship with specific viral markers.

Official Title
-----------------
An Exploratory Case-Control Study of Genetic and Clinical Factors for Serious Cutaneous Reactions Among Users of Eslicarbazepine Acetate

Conditions
-----------------
SCAR

Intervention / Treatment
-----------------
* Other: Blood or Saliva


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Study subjects must have the ability to comprehend the informed consent and be willing to provide informed consent and consent for storage and DNA testing of blood or saliva. For subjects who are unable to comprehend the written consent, a legal guardian who is able to describe and provide an understanding of the informed consent to the subject must sign all study consent forms on behalf of the subject. The study subject or parent/guardian must possess an educational level and degree of understanding of English or Spanish that enables them to communicate suitably with the local investigator and study coordination staff. Specific criteria for cases and controls: Cases will be individuals with documented definite or probable Stevens-Johnson syndrome (SJS) Toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), or drug reaction with eosinophilia and systemic symptoms (DRESS) Symptom onset consistent with one of these conditions within the first 4 months of using ESL (including up to 14 days after discontinuing ESL). Controls will be individuals who have used ESL for at least 6 weeks and who have not developed SCAR. Exclusion Criteria:
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case<br>Cases will be individuals with documented definite or probable Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), or drug reaction with eosinophilia and systemic symptoms (DRESS) or symptom onset consistent with one of these conditions within the first 4 months of using ESL (including up to 14 days after discontinuing ESL) will be considered a potential case. Blood draw or Saliva. | Other: Blood or Saliva<br>* To screen for HLA genotypes that may place patients at high risk of SCAR when they use ESL.<br>|
| Control<br>Controls will be individuals who have used ESL for at least 6 weeks and who have not developed SCAR. Blood draw or saliva. | Other: Blood or Saliva<br>* To screen for HLA genotypes that may place patients at high risk of SCAR when they use ESL.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe Cutaneous Adverse Reactions (SCAR) while using ESL |  | up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HLA genotypes that may place patients at high risk of SCAR when they use ESL. |  | up to 4 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Epilepsy, Genetic associations with severe Cutaneous Adverse Reactions