Trial reportJournal of neurodevelopmental disorders2022
A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX).
Trial report in Journal of neurodevelopmental disorders, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03614663 (A Randomized, Double-Blind, Placebo-Controlled Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With Fragile X Syndrome), which is not on this map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Placebo-Controlled Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With Fragile X Syndrome
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Pooled it
- Parent-Reported Outcome Measures for Individuals with Fragile X Syndrome: Clinically Meaningful Change Thresholds.Journal of autism and developmental disorders · 2026Trial
- Phase 2, open-label INSPIRE trial to assess the tolerability and effectiveness of transdermal cannabidiol gel in children and adolescents with 22q11.2 deletion syndrome (ZYN2-CL-031).Journal of neurodevelopmental disorders · 2026Trial
- 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.Journal of neurodevelopmental disorders · 2025Trial
- Effects of AFQ056 on language learning in fragile X syndrome.The Journal of clinical investigation · 2023Trial
- Caregiver-perceived behavioral challenges in fragile X syndrome and implications for measuring treatment benefit in clinical trials.Journal of patient-reported outcomes · 2026Article
- Clinical Trial Designs for Rare Disorders: A Scoping Review of the Effectiveness of Pharmacologic Interventions in Fragile X Syndrome.Neurology. Genetics · 2026Review
- Cannabinoid Therapies in Less-Common Disorders: Clinical Evidence and Formulation Strategies.Diseases (Basel, Switzerland) · 2026Review
- Parallel paths: A narrative review exploring autism and its co-occurring conditions.World journal of clinical pediatrics · 2025Review
- Behaviours that challenge in children with intellectual disability: systematic review and meta-analysis of pharmacological and non-pharmacological interventions.BJPsych open · 2025Review
- The Current State of Unapproved Cannabidiol Product Use in Children.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- The Aberrant Behavior Checklist for Fragile X Syndrome: A Qualitative Clinician Evaluation of Content Validity.Journal of child and adolescent psychopharmacology · 2025Article
- Article
- From Discovery to Innovative Translational Approaches in 80 Years of Fragile X Syndrome Research.Biomedicines · 2025Review
- Neurobehavioral Outcomes Relate to Activation Ratio in Female Carriers of Fragile X Syndrome Full Mutation: Two Pediatric Case Studies.International journal of molecular sciences · 2025Article
- Novel p.Arg534del Mutation and MTHFR C667T Polymorphism in Fragile X Syndrome (FXS) With Autism Spectrum Phenotype: A Case Report.Case reports in genetics · 2025Article
- Prevalence of Fragile X syndrome in Georgian patients with autism spectrum disorder and/or intellectual disability: cross-sectional study and review of current approaches.Frontiers in pediatrics · 2025Article
- Review
- Cannabinoids for treating psychiatric disorders in youth: a systematic review of randomized controlled trials.Child and adolescent psychiatry and mental health · 2024Review
- Drug Treatments for Neurodevelopmental Disorders: Targeting Signaling Pathways and Homeostasis.Current neurology and neuroscience reports · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy.
designCONNECT-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.
methodsPatients 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
resultsA 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%).
conclusionsIn 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 registrationThe CONNECT-FX trial is registered on Clinicaltrials.gov (NCT03614663).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.