[article]
| Titre : |
A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX) |
| Type de document : |
texte imprimé |
| Auteurs : |
Elizabeth BERRY-KRAVIS, Auteur ; Randi HAGERMAN, Auteur ; Dejan BUDIMIROVIC, Auteur ; Craig ERICKSON, Auteur ; Helen HEUSSLER, Auteur ; Nicole TARTAGLIA, Auteur ; Jonathan COHEN, Auteur ; Flora TASSONE, Auteur ; Thomas DOBBINS, Auteur ; Elizabeth MERIKLE, Auteur ; Terri SEBREE, Auteur ; Nancy TICH, Auteur ; Joseph M. PALUMBO, Auteur ; Stephen O'QUINN, Auteur |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Child Male Humans Adolescent Female Fragile X Syndrome/drug therapy/genetics Cannabidiol/pharmacology/therapeutic use DNA Methylation Behavioral Symptoms Gels/therapeutic use Fragile X Mental Retardation Protein/genetics Cannabidiol Clinical trial Endocannabinoid system Fragile X syndrome for the conduct of the study as investigators and are on scientific advisory board for fragile X syndrome for Zynerba Pharmaceuticals. DB, HH, JC, and FT have received funding from Zynerba Pharmaceuticals for the conduct of the study as investigators. TD and EM are paid consultants for Zynerba Pharmaceuticals. TS, NTich, and SO’Q are employees of Zynerba Pharmaceuticals. JMP was an employee of Zynerba Pharmaceuticals at the time of the study. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: Fragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy. DESIGN: CONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral symptoms in children and adolescents with FXS. METHODS: Patients were randomized to 12 weeks of ZYN002 (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care. The primary endpoint assessed change in social avoidance (SA) measured by the Aberrant Behavior Checklist-Community Edition FXS (ABC-C(FXS)) SA subscale in a full cohort of patients with a FXS full mutation, regardless of the FMR1 methylation status. Ad hoc analyses assessed efficacy in patients with ≥ 90% and 100% methylation of the promoter region of the FMR1 gene, in whom FMR1 gene silencing is most likely. RESULTS: A total of 212 patients, mean age 9.7 years, 75% males, were enrolled. A total of 169 (79.7%) patients presented with ≥ 90% methylation of the FMR1 promoter and full mutation of FMR1. Although statistical significance for the primary endpoint was not achieved in the full cohort, significant improvement was demonstrated in patients with ≥ 90% methylation of FMR1 (nominal P = 0.020). This group also achieved statistically significant improvements in Caregiver Global Impression-Change in SA and isolation, irritable and disruptive behaviors, and social interactions (nominal P-values: P = 0.038, P = 0.028, and P = 0.002). Similar results were seen in patients with 100% methylation of FMR1. ZYN002 was safe and well tolerated. All treatment-emergent adverse events (TEAEs) were mild or moderate. The most common treatment-related TEAE was application site pain (ZYN002: 6.4%; placebo: 1.0%). CONCLUSIONS: In CONNECT-FX, ZYN002 was well tolerated in patients with FXS and demonstrated evidence of efficacy with a favorable benefit risk relationship in patients with ≥ 90% methylation of the FMR1 gene, in whom gene silencing is most likely, and the impact of FXS is typically most severe. TRIAL REGISTRATION: The CONNECT-FX trial is registered on Clinicaltrials.gov (NCT03614663). |
| En ligne : |
https://dx.doi.org/10.1186/s11689-022-09466-6 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 |
in Journal of Neurodevelopmental Disorders > 14 (2022)
[article] A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX) [texte imprimé] / Elizabeth BERRY-KRAVIS, Auteur ; Randi HAGERMAN, Auteur ; Dejan BUDIMIROVIC, Auteur ; Craig ERICKSON, Auteur ; Helen HEUSSLER, Auteur ; Nicole TARTAGLIA, Auteur ; Jonathan COHEN, Auteur ; Flora TASSONE, Auteur ; Thomas DOBBINS, Auteur ; Elizabeth MERIKLE, Auteur ; Terri SEBREE, Auteur ; Nancy TICH, Auteur ; Joseph M. PALUMBO, Auteur ; Stephen O'QUINN, Auteur. Langues : Anglais ( eng) in Journal of Neurodevelopmental Disorders > 14 (2022)
| Mots-clés : |
Child Male Humans Adolescent Female Fragile X Syndrome/drug therapy/genetics Cannabidiol/pharmacology/therapeutic use DNA Methylation Behavioral Symptoms Gels/therapeutic use Fragile X Mental Retardation Protein/genetics Cannabidiol Clinical trial Endocannabinoid system Fragile X syndrome for the conduct of the study as investigators and are on scientific advisory board for fragile X syndrome for Zynerba Pharmaceuticals. DB, HH, JC, and FT have received funding from Zynerba Pharmaceuticals for the conduct of the study as investigators. TD and EM are paid consultants for Zynerba Pharmaceuticals. TS, NTich, and SO’Q are employees of Zynerba Pharmaceuticals. JMP was an employee of Zynerba Pharmaceuticals at the time of the study. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: Fragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy. DESIGN: CONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral symptoms in children and adolescents with FXS. METHODS: Patients were randomized to 12 weeks of ZYN002 (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care. The primary endpoint assessed change in social avoidance (SA) measured by the Aberrant Behavior Checklist-Community Edition FXS (ABC-C(FXS)) SA subscale in a full cohort of patients with a FXS full mutation, regardless of the FMR1 methylation status. Ad hoc analyses assessed efficacy in patients with ≥ 90% and 100% methylation of the promoter region of the FMR1 gene, in whom FMR1 gene silencing is most likely. RESULTS: A total of 212 patients, mean age 9.7 years, 75% males, were enrolled. A total of 169 (79.7%) patients presented with ≥ 90% methylation of the FMR1 promoter and full mutation of FMR1. Although statistical significance for the primary endpoint was not achieved in the full cohort, significant improvement was demonstrated in patients with ≥ 90% methylation of FMR1 (nominal P = 0.020). This group also achieved statistically significant improvements in Caregiver Global Impression-Change in SA and isolation, irritable and disruptive behaviors, and social interactions (nominal P-values: P = 0.038, P = 0.028, and P = 0.002). Similar results were seen in patients with 100% methylation of FMR1. ZYN002 was safe and well tolerated. All treatment-emergent adverse events (TEAEs) were mild or moderate. The most common treatment-related TEAE was application site pain (ZYN002: 6.4%; placebo: 1.0%). CONCLUSIONS: In CONNECT-FX, ZYN002 was well tolerated in patients with FXS and demonstrated evidence of efficacy with a favorable benefit risk relationship in patients with ≥ 90% methylation of the FMR1 gene, in whom gene silencing is most likely, and the impact of FXS is typically most severe. TRIAL REGISTRATION: The CONNECT-FX trial is registered on Clinicaltrials.gov (NCT03614663). |
| En ligne : |
https://dx.doi.org/10.1186/s11689-022-09466-6 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 |
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