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

NCT04988867 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: ACP-2566-009
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Rett Syndrome

Outcome Measures

Primary Outcomes (5)

• Safety and Tolerability of Treatment With Oral Trofinetide

  Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), withdrawals due to AEs, potentially clinically important (PCI) changes in other safety assessments (laboratory values, vital signs, or ECGs, following protocol-defined PCI criteria)

  Mean study drug exposure 434 days, corresponding to 1.2 years

• AUC0-12,ss (Area Under the Concentration-time Curve From Time 0 to 12 h at Steady State)

  Area under the concentration-time curve from time 0 to 12 h at steady state as obtained from population pharmacokinetic (PK) modelling

  PK samples were taken predose and at Weeks 2, 4, 8, and 12

• Cmax,ss (Maximum Observed Drug Concentration at Steady State)

  Maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling

  PK samples were taken predose and at Weeks 2, 4, 8, and 12

• Cmin,ss (Minimum Observed Drug Concentration at Steady State of Oral Trofinetide)

  Minimum observed drug concentration at steady state of oral trofinetide as obtained from population pharmacokinetic (PK) modeling

  PK samples were taken predose and at Weeks 2, 4, 8, and 12

• Tmax (Time of the Maximum Observed Drug Concentration at Steady State)

  Time of the maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling

  PK samples were taken predose and at Weeks 2, 4, 8, and 12

Study Arms (1)

Drug - trofinetide

EXPERIMENTAL

Oral dose of trofinetide

Drug: Trofinetide

Interventions

Trofinetide DRUG

Trofinetide solution of 10-30 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)

Drug - trofinetide

Eligibility Criteria

• Age: 2 Years - 5 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Female subject
• to 4 years of age and body weight ≥9 kg and \<20 kg at Screening OR
• 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

You may not qualify if:

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

Sponsors & Collaborators

• ACADIA Pharmaceuticals Inc.: lead

Study Sites (7)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Boston Children's Hospital/Harvard Medical School

Boston, Massachusetts, 02115, United States

Location

Gillette Children's Hospital

Saint Paul, Minnesota, 55101, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (2)

• Percy AK, Ryther R, Marsh ED, Neul JL, Benke TA, Berry-Kravis EM, Feyma T, Lieberman DN, Ananth AL, Fu C, Buhrfiend C, Barrett A, Doshi D, Darwish M, An D, Bishop KM, Youakim JM. Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome. Med. 2025 Jun 13;6(6):100608. doi: 10.1016/j.medj.2025.100608. Epub 2025 Mar 4.

  PMID: 40043705 DERIVED

• Parent H, Ferranti A, Niswender C. Trofinetide: a pioneering treatment for Rett syndrome. Trends Pharmacol Sci. 2023 Oct;44(10):740-741. doi: 10.1016/j.tips.2023.06.008. Epub 2023 Jul 16.

  PMID: 37460385 DERIVED

MeSH Terms

Conditions

Rett Syndrome

Interventions

trofinetide

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Limitations and Caveats

As a result of marketing approval of trofinetide on 10 March 2023, the study was terminated by the Sponsor with the intent of switching patients to commercially available product. The study was terminated on 31 May 2023.

Results Point of Contact

• Title: Sr. Dir. Medical Information and Medical Communications
• Organization: ACADIA Pharmaceuticals Inc.

medicalinformation@acadia-pharm.com

+1-858-261

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2021
• First Posted: August 4, 2021
• Study Start: September 22, 2021
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2023
• Last Updated: September 24, 2024
• Results First Posted: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)