[article]
| Titre : |
Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study |
| Type de document : |
texte imprimé |
| Auteurs : |
Elizabeth BERRY-KRAVIS, Auteur ; Randi HAGERMAN, Auteur ; Jonathan COHEN, Auteur ; Dejan BUDIMIROVIC, Auteur ; Caroline B. BUCHANAN, Auteur ; Natalie SILOVE, Auteur ; Nancy TICH, Auteur ; Anthony THIBODEAU, Auteur ; Thomas DOBBINS, Auteur ; Terri SEBREE, Auteur ; Stephen O'QUINN, Auteur ; David S. ALBERS, Auteur ; Kristen G. BZDEK, Auteur ; George NOMIKOS, Auteur ; Kumar BUDUR, Auteur |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Humans Fragile X Syndrome/drug therapy Adolescent Child Male Administration, Cutaneous Cannabidiol/administration & dosage/adverse effects Female Gels Child, Preschool Endocannabinoid system Fragile x syndrome Irritability Social avoidance Transdermal cannabidiol conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and was approved by Advarra, Inc. Institutional Review Board (IRB Approval Number: Pro00060799. Consent for publication: Not applicable. Competing interests: EB-K, RH, JC, DB, CBB, and NS have received funding from Harmony Biosciences for the conduct of this trial as investigators. TD, TS, and SOQ are paid consultants of Harmony Biosciences. CBB is a paid consultant of Acadia Pharmaceuticals. NT, AT, DSA, KGB, GN, and KB are employees of Harmony Biosciences. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: Dysregulated endocannabinoid signaling is involved in Fragile X syndrome (FXS), suggesting a potential role for the endocannabinoid signaling modulator, cannabidiol, in treatment. ZYN002 is a synthetic cannabidiol that has been uniquely formulated as a gel for transdermal delivery and is currently under investigation for the treatment of behavioral symptoms associated with FXS. DESIGN: ZYN2-CL-017 is an ongoing, long-term, open-label extension (OLE) safety trial of ZYN002 in patients with FXS. We are enrolling patients from past and current ZYN002 clinical trials to evaluate the safety and tolerability of ZYN002 in patients with FXS. METHODS: Primary safety assessments were conducted in patients who enrolled into the OLE from 2 completed ZYN002 trials. Secondary analyses, conducted in a subgroup enrolled from a completed placebo-controlled trial of ZYN002, included the FXS-specific Aberrant Behavior Checklist-Community Social Avoidance and Irritability subscales (ABC-C(FXS) SA and ABC-C(FXS) Irr, examined change from baseline of the randomized study) and the Caregiver Global Impression of Change (CaGI-C, examined change from baseline of the OLE), in which caregivers were asked to rate the change in their child's overall behavior. RESULTS: At the time of this interim analysis data cut (January 31, 2024), 240 patients had been enrolled from 2 completed ZYN002 trials. Mean age at entry to the OLE was 9.7 years (range 3-17 years), and the majority were male (76.3%) and White (80.4%). Mean exposure to ZYN002 during the initial trials and OLE was 28 months. Treatment-related adverse events (AEs) were reported in 12.9% of patients; the most common (6.7% of patients) was short-term application site pain. The highest degree of skin irritation reported by investigators was moderate erythema in 7 patients (2.9%). In the secondary analysis cohort (n=196 evaluable patients), patients demonstrated clinically meaningful changes in ABC-C(FXS) SA, ABC-C(FXS) Irr, and CaGI-C scores. CONCLUSIONS: Interim analysis results of the ongoing OLE in children, adolescents, and young adults with FXS demonstrated that ZYN002 has a favorable long-term safety profile and is generally well tolerated. Clinically meaningful changes in behaviors from baseline continued to be observed during the OLE. These findings support further study of ZYN002 in patients with FXS. TRIAL REGISTRATION: ZYN2-CL-017 is registered on Clinicaltrials.gov (NCT03802799) on December 26, 2018. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-025-09657-x |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 |
in Journal of Neurodevelopmental Disorders > 17 (2025)
[article] Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study [texte imprimé] / Elizabeth BERRY-KRAVIS, Auteur ; Randi HAGERMAN, Auteur ; Jonathan COHEN, Auteur ; Dejan BUDIMIROVIC, Auteur ; Caroline B. BUCHANAN, Auteur ; Natalie SILOVE, Auteur ; Nancy TICH, Auteur ; Anthony THIBODEAU, Auteur ; Thomas DOBBINS, Auteur ; Terri SEBREE, Auteur ; Stephen O'QUINN, Auteur ; David S. ALBERS, Auteur ; Kristen G. BZDEK, Auteur ; George NOMIKOS, Auteur ; Kumar BUDUR, Auteur. Langues : Anglais ( eng) in Journal of Neurodevelopmental Disorders > 17 (2025)
| Mots-clés : |
Humans Fragile X Syndrome/drug therapy Adolescent Child Male Administration, Cutaneous Cannabidiol/administration & dosage/adverse effects Female Gels Child, Preschool Endocannabinoid system Fragile x syndrome Irritability Social avoidance Transdermal cannabidiol conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and was approved by Advarra, Inc. Institutional Review Board (IRB Approval Number: Pro00060799. Consent for publication: Not applicable. Competing interests: EB-K, RH, JC, DB, CBB, and NS have received funding from Harmony Biosciences for the conduct of this trial as investigators. TD, TS, and SOQ are paid consultants of Harmony Biosciences. CBB is a paid consultant of Acadia Pharmaceuticals. NT, AT, DSA, KGB, GN, and KB are employees of Harmony Biosciences. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: Dysregulated endocannabinoid signaling is involved in Fragile X syndrome (FXS), suggesting a potential role for the endocannabinoid signaling modulator, cannabidiol, in treatment. ZYN002 is a synthetic cannabidiol that has been uniquely formulated as a gel for transdermal delivery and is currently under investigation for the treatment of behavioral symptoms associated with FXS. DESIGN: ZYN2-CL-017 is an ongoing, long-term, open-label extension (OLE) safety trial of ZYN002 in patients with FXS. We are enrolling patients from past and current ZYN002 clinical trials to evaluate the safety and tolerability of ZYN002 in patients with FXS. METHODS: Primary safety assessments were conducted in patients who enrolled into the OLE from 2 completed ZYN002 trials. Secondary analyses, conducted in a subgroup enrolled from a completed placebo-controlled trial of ZYN002, included the FXS-specific Aberrant Behavior Checklist-Community Social Avoidance and Irritability subscales (ABC-C(FXS) SA and ABC-C(FXS) Irr, examined change from baseline of the randomized study) and the Caregiver Global Impression of Change (CaGI-C, examined change from baseline of the OLE), in which caregivers were asked to rate the change in their child's overall behavior. RESULTS: At the time of this interim analysis data cut (January 31, 2024), 240 patients had been enrolled from 2 completed ZYN002 trials. Mean age at entry to the OLE was 9.7 years (range 3-17 years), and the majority were male (76.3%) and White (80.4%). Mean exposure to ZYN002 during the initial trials and OLE was 28 months. Treatment-related adverse events (AEs) were reported in 12.9% of patients; the most common (6.7% of patients) was short-term application site pain. The highest degree of skin irritation reported by investigators was moderate erythema in 7 patients (2.9%). In the secondary analysis cohort (n=196 evaluable patients), patients demonstrated clinically meaningful changes in ABC-C(FXS) SA, ABC-C(FXS) Irr, and CaGI-C scores. CONCLUSIONS: Interim analysis results of the ongoing OLE in children, adolescents, and young adults with FXS demonstrated that ZYN002 has a favorable long-term safety profile and is generally well tolerated. Clinically meaningful changes in behaviors from baseline continued to be observed during the OLE. These findings support further study of ZYN002 in patients with FXS. TRIAL REGISTRATION: ZYN2-CL-017 is registered on Clinicaltrials.gov (NCT03802799) on December 26, 2018. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-025-09657-x |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 |
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Faire une suggestion Affiner la rechercheLong-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study / Elizabeth BERRY-KRAVIS in Journal of Neurodevelopmental Disorders, 17 (2025)
