Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome

Academic Article


  • ObjectiveTo determine safety, tolerability, and pharmacokinetics of trofinetide and evaluate its efficacy in female children/adolescents with Rett syndrome (RTT), a debilitating neurodevelopmental condition for which no pharmacotherapies directed at core features are available.MethodsThis was a phase 2, multicenter, double-blind, placebo-controlled, parallel-group study, in which safety/tolerability, pharmacokinetics, and clinical response to trofinetide were characterized in 82 children/adolescents with RTT, aged 5 to 15 years. Sixty-Two participants were randomized 1:1:1:1 to receive placebo twice a day (bid) for 14 days, followed by placebo, 50, 100, or 200 mg/kg bid of trofinetide for 42 days. Following blinded safety data review, 20 additional participants were randomized 1:1 to the 200 mg/kg or placebo bid groups. Safety assessments included adverse events, clinical laboratory tests, physical examinations, and concomitant medications. Clinician-and caregiver-based efficacy measurements assessed clinically relevant, phenotypic dimensions of impairment of RTT.ResultsAll dose levels were well tolerated and generally safe. Trofinetide at 200 mg/kg bid showed statistically significant and clinically relevant improvements relative to placebo on the Rett Syndrome Behaviour Questionnaire, RTT-Clinician Domain Specific Concerns-Visual Analog Scale, and Clinical Global Impression Scale-Improvement. Exploratory analyses suggested that observed changes correlated with trofinetide exposure.ConclusionThese results, together with those from a previous adolescent/adult trial, indicate trofinetide's potential for treating core RTT symptoms and support further trials.Classification of evidenceThis study provides Class I evidence that for children/adolescents with RTT, trofinetide was safe, well-Tolerated, and demonstrated improvement over placebo at 200 mg/kg bid in functionally important dimensions of RTT.
  • Authors

    Published In

  • Neurology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Glaze DG; Neul JL; Kaufmann WE; Berry-Kravis E; Condon S; Stoms G; Oosterholt S; Della Pasqua O; Glass L; Jones NE
  • Start Page

  • E1912
  • End Page

  • E1925
  • Volume

  • 92
  • Issue

  • 16