Rett syndrome (RTT) is a significantly debilitating neurodevelopmental disorder with no approved treatments.

Trofinetide is a synthetic analog of glycine-proline-glutamate (GPE), the N-terminal tripeptide of the insulin-like growth factor 1 (IGF-1) (Guan et al., 2015).

A recent Phase 2 clinical study evaluated treatment with trofinetide versus placebo in 82 females with RTT aged 5 to 15 years (Glaze et al., 2019). At the highest dose (200 mg/kg BID), a benefit for trofinetide was observed compared with placebo on 3 of 5 measures: the Rett Syndrome Behavior Questionnaire (RSBQ) (P=0.042), the Clinical Global Impressions-Improvement (CGI-I, P=0.029), and the RTT-Clinician Domain Specific Concerns-Visual Analog Scale (P=0.025). Trofinetide was well tolerated at all doses (50, 100, and 200 mg/kg BID).

This 12-week, double-blind, randomized, placebo-controlled study will evaluate efficacy and safety of trofinetide in 180 females 5 to 20 years old with RTT. The RSBQ and the CGI-I syndrome-specific efficacy measures are the co-primary efficacy endpoints. Additionally, secondary endpoints will leverage novel and existing scales to evaluate the impact of trofinetide on other core symptoms of Rett syndrome, including patients’ ability to communicate, overall quality of life, hand function, and burden on caregivers. This study will be followed by a 40-week open-label extension study.

Trial results are not yet available.