CONNECTA Therapeutics has started a Phase 2a clinical trial of its lead candidate CTH120 in adults with fragile X syndrome, advancing a programme that aims to target disrupted neuroplasticity in the rare neurodevelopmental disorder.

The study follows positive Phase 1 safety findings and will evaluate the investigational small molecule in 30 adult male participants with fragile X syndrome, a condition that currently has no approved targeted disease-modifying treatments.

CTH120 is designed to target tropomyosin receptor kinase B (TrkB), a regulator of neuroplasticity that is involved in the brain’s ability to form and adapt neural connections. According to CONNECTA, impaired neuroplasticity is a key feature of fragile X syndrome and contributes to the cognitive and behavioural symptoms associated with the condition.

The randomized, double-blind, placebo-controlled, parallel-group study will compare twice-daily CTH120 with placebo in a 1:1 ratio. The primary endpoint is safety and tolerability, while secondary endpoints include pharmacokinetics and clinical efficacy measures.

The trial will enrol adult males aged between 18 and 45 years, reflecting the fact that fragile X syndrome is an X-linked disorder that often presents more severely in men.

Jordi Fàbrega, co-founder and chief executive officer of CONNECTA Therapeutics, said: “Building on encouraging Phase I safety data, this trial is designed to further evaluate the safety and tolerability of CTH120 and to generate critical insights into its potential therapeutic benefit by modulating pathways implicated in disrupted neuronal function in FXS.”

He added: “We believe this study could support the development of a novel, disease-modifying approach for FXS and serve as an important proof point for our broader neuroplasticity modulation platform.”

Fragile X syndrome is the most common inherited cause of intellectual disability and is estimated to affect around three in every 10,000 people. The disorder results from mutations in the FMR1 gene and can cause learning difficulties, behavioural challenges and developmental delays.

The Phase 2a study will be conducted at Hospital del Mar Research Institute in Barcelona and the Parc Taulí Research and Innovation Institute Foundation in Sabadell, Spain. Researchers will also investigate disease-specific biomarkers that could improve understanding of fragile X syndrome biology and treatment response.

Rafael de la Torre Fornell, principal investigator and study coordinator at Hospital del Mar Research Institute, said: “FXS has a profound impact on cognitive and behavioral function, severely affecting the quality of life of individuals living with the condition and their families. It remains a condition with significant unmet medical need, with no approved disease-modifying treatments.”

He added: “This Phase IIa trial provides an important opportunity to evaluate a promising new mechanism of action and advance clinical understanding of this lifelong condition.”

The study has received authorization from the Spanish Agency of Medicines and Medical Devices and the relevant ethics committees. Funding is being provided by the Spanish Ministry of Science, Innovation and Universities together with the European Union’s NextGeneration EU programme.

Successful completion of the trial would provide additional safety and efficacy data to inform the future clinical development of CTH120 as CONNECTA continues to investigate neuroplasticity modulation as a potential therapeutic strategy for central nervous system disorders.