An Open-Label Study of Trofinetide for the Treatment of Girls Two to Five Years of Age Who Have Rett Syndrome (DAFFODIL™)

To investigate the safety and tolerability of long-term treatment with oral trofinetide in girls with Rett syndrome

Study Overview

• Status: Completed
• Conditions: Rett Syndrome
• Intervention / Treatment: Drug: Trofinetide

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital/Harvard Medical School
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Gillette Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female subject

  1. 2 to 4 years of age and body weight ≥9 kg and <20 kg at Screening OR
  2. 5 years of age and body weight ≥9 kg and <12 kg at Screening
• Can swallow the study medication provided as a liquid solution or can take it by gastrostomy tube
• The subject's caregiver is English-speaking and has sufficient language skills to complete the caregiver assessments
• Has classic/typical Rett syndrome (RTT) or possible RTT according to the Rett Syndrome Diagnostic Criteria
• Has a documented disease-causing mutation in the MECP2 gene
• Has a stable pattern of seizures, or has had no seizures, within 8 weeks prior to Screening
• Subject and caregiver(s) must reside at a location to which study drug can be delivered and have been at their present residence for at least 4 weeks prior to Screening

Exclusion Criteria:

• Has been treated with insulin within 12 weeks of Baseline
• Has current clinically significant cardiovascular, endocrine (such as hypo- or hyperthyroidism, Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus), renal, hepatic, respiratory or gastrointestinal disease (such as celiac disease or inflammatory bowel disease) or has major surgery planned during the study
• Has a history of, or current, cerebrovascular disease or brain trauma
• Has significant, uncorrected visual or uncorrected hearing impairment
• Has a history of, or current, malignancy

• Has any of the following:

  1. QTcF interval of >450 ms at Screening or Baseline
  2. History of a risk factor for torsades de pointes (e.g., heart failure or family history of long QT syndrome)
  3. History of clinically significant QT prolongation that is deemed to put the subject at increased risk of clinically significant QT prolongation
  4. Other clinically significant finding on ECG at Screening or Baseline

Additional inclusion/exclusion criteria apply. Patients will be evaluated at baseline to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically, if it is determined that their baseline health and condition do not meet all prespecified entry criteria).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug - trofinetide; Oral dose of trofinetide	Drug: Trofinetide; Trofinetide solution of 10-30 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of treatment with oral trofinetide	Percentage of subjects with Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), withdrawals due to AEs, potentially clinically important changes in other safety assessments	Approximately 24 Months Treatment Duration
Whole blood concentration of oral trofinetide		Pre-dose and Weeks 2, 4, 8, and 12
Area under the plasma concentration-time curve (AUC)		Pre-dose and Weeks 2, 4, 8, and 12
Maximum (peak) observed drug concentration (Cmax)		Pre-dose and Weeks 2, 4, 8, and 12
Apparent terminal elimination half-life (t½)		Pre-dose and Weeks 2, 4, 8, and 12

Collaborators and Investigators

• Sponsor: ACADIA Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2021
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: July 23, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 4, 2021

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome
• Other Study ID Numbers: ACP-2566-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No