Open-Label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome

NCT04279314 | Completed Phase 3 Results FDA Drug

• 1 other identifier: ACP-2566-004
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 21

Brief Summary

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

Conditions

Rett Syndrome

Outcome Measures

Primary Outcomes (5)

• Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs), Percentage of Subjects With Serious Adverse Events (SAEs), and Percentage of Subjects With Withdrawals Due to AEs

  Percentage of subjects with treatment-emergent adverse events (TEAEs), percentage of subjects with serious adverse events (SAEs), and percentage of subjects with withdrawals due to AEs

  40 Weeks Treatment Duration

• Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in ECG

  Potentially clinically important ECG changes were defined in the study protocol as absolute QTcF interval \>500 ms or QTcF interval change from the baseline value of previous study ACP-2566-003 of \>60 ms

  40 Weeks Treatment Duration

• Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Vital Signs

  Potentially clinically important changes in vital signs were defined in the study protocol as: systolic blood pressure (SBP) ≥180 mmHg and increased ≥20 mmHg from baseline; SBP ≤90 mmHg and decreased ≥20 mmHg from baseline; diastolic blood pressure (DBP) ≥ 105 mmHg and increased ≥15 mmHg from baseline; DBP ≤50 mmHg and decreased ≥15 mmHg from baseline; Pulse ≥120 bpm and increased ≥15 bpm from baseline; Pulse ≤50 bpm and decreased ≥15 bpm from baseline

  40 Weeks Treatment Duration

• Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Body Weight

  Potentially clinically important changes in body weight were defined in the study protocol as: Weight increase ≥7% from baseline; Weight decrease ≥7% from baseline

  40 Weeks Treatment Duration

• Subjects (N, %) With Post-baseline Potentially Clinically Important Changes

  Potentially clinically important changes in laboratory parameters were defined in the study protocol as: Sodium ≤125 mmol/L; Sodium ≥155 mmol/L; Potassium ≤3.0 mmol/L; Potassium ≥5.5 mmol/L; Chloride ≤85 mmol/L; Chloride ≥120 mmol/L; Calcium \<2.0 mmol/L; Calcium \>2.0 mmol/L; Blood urea nitrogen ≥10.71 mmol/L; Creatinine \>1.5 x upper limit of normal (ULN); Uric acid ≥505.75 μmol/L; Lactate dehydrogenase ≥3 x ULN; Glucose ≤2.48 mmol/L; Glucose ≥11 mmol/L; Albumin ≤26 g/L; Albumin ≥60 g/L; Protein ≤50 g/L; Protein ≥100 g/L; Alanine aminotransferase ≥3 x ULN; Aspartate aminotransferase ≥3 x ULN; Gamma glutamyl transpeptidase ≥3 x ULN; Alkaline phosphatase ≥3 x ULN; Bilirubin ≥1.5 x ULN

  40 Weeks Treatment Duration

Secondary Outcomes (11)

• Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score Change From Baseline to Week 40

  40 Weeks Treatment Duration

• Clinical Global Impression-Improvement (CGI-I) Score at Week 40

  40 Weeks Treatment Duration

• Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social) Change From Baseline to Week 40

  40 Weeks Treatment Duration

• Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND) Change From Baseline to Week 40

  40 Weeks Treatment Duration

• Rett Syndrome Clinician Rating of Hand Function (RTT-HF) Change From Baseline to Week 40

  40 Weeks Treatment Duration

Study Arms (1)

Trofinetide

EXPERIMENTAL

Drug: Trofinetide

Interventions

Trofinetide DRUG

Trofinetide solution of 30-60 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)

Trofinetide

Eligibility Criteria

• Age: 5 Years - 21 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Has completed the Week 12/End-of-treatment visit of the antecedent study, Study ACP-2566-003
• Met all entry criteria for the antecedent study
• May benefit from long-term treatment with open-label trofinetide in the judgment of the Investigator
• Can still 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
• 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 3 months prior to Baseline

You may not qualify if:

• Began treatment with growth hormone during the antecedent study
• Began treatment with IGF-1 during the antecedent study
• Began treatment with insulin during the antecedent study
• Has developed a 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
• Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study due to AEs, medical condition, or noncompliance with investigational product or study procedures in the antecedent study
• Has a clinically significant abnormality in vital signs at Baseline
• Has a QTcF interval of \>450 ms on the Baseline ECG performed before the first dose of trofinetide is given in the present study
• Has developed a clinically significant ECG finding during the antecedent study

Sponsors & Collaborators

• ACADIA Pharmaceuticals Inc.: lead

Study Sites (21)

University of Alabama at Birmingham

Birmingham, Alabama, 35223, United States

Location

Translational Genomics Research Institute (TGen)

Phoenix, Arizona, 85012, United States

Location

University of California, San Diego

La Jolla, California, 92093, United States

Location

UC Davis MIND Institute

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children Medical Services

Tampa, Florida, 33606, United States

Location

Emory Genetics Clinical Trial Center

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Kennedy Krieger Institute - Clinical Trials Unit

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, 55101, United States

Location

Washington University School of Medicine, St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Montefiore Medical Center, Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Greenwood Genetic Center

Greenwood, South Carolina, 29626, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's

Seattle, Washington, 98105, United States

Location

Related Publications (2)

• Percy AK, Neul JL, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, An D, Bishop KM, Youakim JM. Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study. Med. 2024 Sep 13;5(9):1178-1189.e3. doi: 10.1016/j.medj.2024.05.018. Epub 2024 Jun 24.

  PMID: 38917793 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

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 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2020
• First Posted: February 21, 2020
• Study Start: January 29, 2020
• Primary Completion: August 19, 2022
• Study Completion: August 19, 2022
• Last Updated: April 11, 2024
• Results First Posted: April 11, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)