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

Phase 2

Completed

• Conditions: Rett Syndrome
• Interventions: Drug: Trofinetide

• Registration Number: NCT04988867
• Lead Sponsor: ACADIA Pharmaceuticals Inc.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-23
• Study First Submitted QC: 2021-08-03
• Study First Posted: 2021-08-04
• Study Start: 2021-09-22
• Primary Completion: 2023-05-31
• Study Completion: 2023-05-31
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-20
• Last Update Posted: 2023-06-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 15

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Drug - trofinetide	Trofinetide	Oral dose of trofinetide

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability of Treatment With Oral Trofinetide	Mean study drug exposure 434 days, corresponding to 1.2 years	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)
AUC0-12,ss (Area Under the Concentration-time Curve From Time 0 to 12 h at Steady State)	PK samples were taken predose and at Weeks 2, 4, 8, and 12	Area under the concentration-time curve from time 0 to 12 h at steady state as obtained from population pharmacokinetic (PK) modelling
Cmax,ss (Maximum Observed Drug Concentration at Steady State)	PK samples were taken predose and at Weeks 2, 4, 8, and 12	Maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling
Cmin,ss (Minimum Observed Drug Concentration at Steady State of Oral Trofinetide)	PK samples were taken predose and at Weeks 2, 4, 8, and 12	Minimum observed drug concentration at steady state of oral trofinetide as obtained from population pharmacokinetic (PK) modeling
Tmax (Time of the Maximum Observed Drug Concentration at Steady State)	PK samples were taken predose and at Weeks 2, 4, 8, and 12	Time of the maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling

Trial Locations

Locations (7)

Gillette Children's Hospital; 🇺🇸 Saint Paul, Minnesota, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Boston Children's Hospital/Harvard Medical School; 🇺🇸 Boston, Massachusetts, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States