All three doses of trofinetide were safe and tolerable. One participant in the 200-mg/kg b.i.d. group was withdrawn from the study at her parents’ request. Serious adverse events occurred in one control participant, one receiving the 100-mg/kg b.i.d. dose, and one receiving the 200-mg/kg b.i.d. dose. These serious adverse events were considered unrelated to study medication and resolved by the study’s end. The most common adverse events were diarrhea, vomiting, upper respiratory tract infection, and pyrexia. Most were mild or moderate and considered unrelated to trofinetide.
The 200-mg/kg b.i.d. dose of trofinetide significantly improved outcomes on the Rett Syndrome Behavior Questionnaire (RSBQ), Clinical Global Impression Scale–Improvement (CGI-I), and Rett Syndrome Domain Specific Concerns (RTT-DSC), compared with placebo. The change of the median RTT-DSC score was 15%, and the change of the mean RSBQ score was 16%. More than 20% of participants receiving 200 mg/kg b.i.d. of trofinetide were rated much improved on the CGI-I, compared with less than 5% of controls.
“Overall, the observed clinical improvement in the present pediatric trial was more manifest than in the previous trial, with younger age (i.e., greater neuroplasticity), higher doses (i.e., higher drug exposure), and longer drug treatment duration (i.e., 28 days in Rett-001 vs. 42 days in Rett-002) as potential contributors,” said Dr. Glaze and his colleagues. “Future studies aiming at replicating the results of this pediatric trial would benefit from including the RSBQ as a primary endpoint and should also consider evaluating RSBQ subscales such as the General Mood.”
Neuren Pharmaceuticals and Rettsyndrome.org funded the study. Dr. Glaze is a consultant to Neuren Pharmaceuticals.
SOURCE: Glaze DG et al. Neurology. 2019 Mar 27. doi: 10.1212/WNL.0000000000007316.