RECONNECT (ZYN2-CL-033): DESIGN OF A PHASE 3 TRIAL OF ZYN002 CANNABIDIOL TRANSDERMAL GEL IN CHILDREN AND ADOLESCENTS WITH FRAGILE X SYNDROME BASED UPON LEARNINGS FROM CONNECT-FX (ZYN2-CL-016)
| Autor: | Nancy Tich, Elizabeth Merikle, Thomas Dobbins, Stephen O'Quinn, Terri B. Sebree, Joseph Palumbo |
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| Rok vydání: | 2021 |
| Předmět: |
education.field_of_study
medicine.medical_specialty business.industry Population Irritability medicine.disease Placebo Fragile X syndrome Psychiatry and Mental health Internal medicine Developmental and Educational Psychology Clinical endpoint Clinical Global Impression Medicine medicine.symptom business education Cannabidiol medicine.drug Transdermal |
| Zdroj: | Journal of the American Academy of Child & Adolescent Psychiatry. 60:S258 |
| ISSN: | 0890-8567 |
| Popis: | Objectives: ZYN002 is a pharmaceutically manufactured transdermal cannabidiol gel in development for the treatment of behavioral symptoms in Fragile X syndrome (FXS). RECONNECT is a pivotal, randomized, double-blind, Phase 3 trial to assess the efficacy and safety of ZYN002 in children/adolescents aged 3 to 17 years with a full FMR1 gene mutation. RECONNECT is designed based on learnings from CONNECT-FX which was completed during the SARS-COV-2 (COVID-19) pandemic in patients with FXS dependent upon caregivers for assessments and support. Methods: The results and conduct of CONNECT-FX were reviewed to identify key learnings to design RECONNECT. Results: Lessons learned: 1) treatment response for ZYN002 was greatest in patients with ≥90% methylation of the FMR1 gene;2) the Aberrant Behavior Checklist–Community FXS Specific (ABC‒CFXS) was determined fit-for-purpose and meaningful within-patient change was determined for the Social Avoidance, Irritability and Socially Unresponsive/Lethargic subscales;3) the Caregiver Global Impression of Severity/Change (CaGI-S/C) were highly responsive to change, with greatest change on the Social Interactions;4) a FXS-specific Clinical Global Impression of Severity/Improvement (CGI-S/I) assessment was developed based upon outcomes in response to FDA guidance to use a disease-specific CGI;and 5) virtual visits were successfully incorporated as a result of COVID-19. Conclusions: RECONNECT will randomly assign approximately 200 patients 1:1 to receive 18-weeks of treatment with ZYN002 or placebo. The primary endpoint is change from baseline in the ABC‒CFXS Social Avoidance subscale at week 18 in patients with complete methylation of the FMR1 gene (100% by methylation PCR). Key secondary endpoints include change from baseline in ABC-CFXS Irritability, improvement in CaGI-C Social Interactions and FXS-specific CGI-I, and change from baseline in ABC-CFXS Social Avoidance in the full population (complete and partial methylation). Four of 8 visits will be virtual to reduce family burden. Results from RECONNECT may provide the data needed to support the potential approval of ZYN002 as the first treatment of the behavioral symptoms associated with FXS. |
| Databáze: | OpenAIRE |
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