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

• ClinicalTrials.gov Identifier: NCT04988867
• Recruitment Status: Active, not recruiting
• First Posted: August 4, 2021
• Last Update Posted: May 6, 2022
• Sponsor: ACADIA Pharmaceuticals Inc.
• Information provided by (Responsible Party): ACADIA Pharmaceuticals Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Rett Syndrome	Drug: Trofinetide	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study of Trofinetide for the Treatment of Girls Two to Five Years of Age Who Have Rett Syndrome
• Actual Study Start Date: September 22, 2021
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: July 2023

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of treatment with oral trofinetide [ Time Frame: Approximately 24 Months Treatment Duration ]
   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
2. Whole blood concentration of oral trofinetide [ Time Frame: Pre-dose and Weeks 2, 4, 8, and 12 ]
3. Area under the plasma concentration-time curve (AUC) [ Time Frame: Pre-dose and Weeks 2, 4, 8, and 12 ]
4. Maximum (peak) observed drug concentration (Cmax) [ Time Frame: Pre-dose and Weeks 2, 4, 8, and 12 ]
5. Apparent terminal elimination half-life (t½) [ Time Frame: Pre-dose and Weeks 2, 4, 8, and 12 ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 5 Years (Child)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, Massachusetts

Boston Children's Hospital/Harvard Medical School

Boston, Massachusetts, United States, 02115

United States, Minnesota

Gillette Children's Hospital

Saint Paul, Minnesota, United States, 55101

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

ACADIA Pharmaceuticals Inc.

More Information

• Responsible Party: ACADIA Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT04988867
• Other Study ID Numbers: ACP-2566-009
• First Posted: August 4, 2021
• Last Update Posted: May 6, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Rett Syndrome; Syndrome; Disease; Pathologic Processes; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System