Open-Label Extension Study of Trofinetide for Rett Syndrome

NCT04776746 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: ACP-2566-005
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 21

Brief Summary

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

Conditions

Rett Syndrome

Outcome Measures

Primary Outcomes (5)

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

  Withdrawals due to AEs included both study drug discontinuation as well as study termination

  Mean study drug exposure was 426 days, corresponding to 1.2 years

• Number (%) of Patients With Potentially Clinically Important Changes in ECG Post-baseline

  Potentially clinically significant ECG changes were defined as QTcF \>500 ms or QTcF change from baseline (CFB) of \>60 ms

  Mean study drug exposure was 426 days, corresponding to 1.2 years

• Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline

  Potentially clinically important changes from baseline in vital signs were defined 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 rate (PR) ≥120 bpm and increased ≥15 bpm from baseline; PR≤50 bpm and decreased ≥15 bpm from baseline. Baseline was the baseline value of previous study ACP-2566-003.

  Mean study drug exposure was 426 days, corresponding to 1.2 years

• Number (%) of Patients With Potentially Clinically Important Changes in Body Weight Post-baseline

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

  Mean study drug exposure was 426 days, corresponding to 1.2 years

• Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline

  Potentially clinically important changes in laboratory parameters were defined 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 \>2.75 mmol/L; blood urea nitrogen ≥10.71 mmol/L; creatinine \>1.5× upper limit of normal (ULN); uric acid ≥505.75 μmol/L; lactate dehydrogenase (LDH) ≥3×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 transaminase (ALT) ≥3×ULN; aspartate transaminase (AST) ≥3×ULN; gamma glutamyl transferase (GGT) ≥3×ULN; alkaline phosphatase (ALP) ≥3×ULN; bilirubin ≥1.5×ULN

  Mean study drug exposure was 426 days, corresponding to 1.2 years

Study Arms (1)

Drug - trofinetide

EXPERIMENTAL

trofinetide oral solution

Drug: trofinetide

Interventions

trofinetide DRUG

Study drug is administered twice a day for up to approximately 32 months. Doses may be taken orally or administered by gastrostomy (G) tube. The subject's assigned dose for this study will be the final dose from the antecedent study (ACP-2566-004).

Drug - trofinetide

Eligibility Criteria

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

You may qualify if:

• Has completed the EOT visit of the antecedent trofinetide Study ACP-2566-004 (i.e., has completed 40 weeks)
• May benefit from continued 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
• Childbearing Potential
• Subjects of childbearing potential must abstain from sexual activity for the duration of the study and for at least 30 days thereafter. If a subject is sexually active or becomes sexually active during the study, she must use 2 clinically acceptable methods of contraception (e.g., oral, intrauterine device \[IUD\], diaphragm plus spermicide, injectable, transdermal or implantable contraception) for the duration of the study and for at least 30 days thereafter. Subject must not be pregnant or breastfeeding.

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)
• 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 an average QTcF interval of \>450 ms on the Baseline ECG performed before the first dose of trofinetide is given in the present study (i.e., the ECG performed at the EOT visit of the antecedent 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, 35233, United States

Location

Translational Genomics Research Institute (TGen)

Phoenix, Arizona, 85012, United States

Location

University of California, San Diego

La Jolla, California, 92037, United States

Location

UC Davis MIND Institute

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado Aurora

Aurora, Colorado, 80045, United States

Location

University of South Florida

Tampa, Florida, 33612, 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, John Hopkins School of Medicine

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital Harvard Medical School

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, Missouri, 63110, United States

Location

Montefiore Medical Center

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, 29646, 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 Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (2)

• Percy AK, Neul JL, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, Barrett AM, An D, Bishop KM, Youakim JM. Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study. Med. 2024 Oct 11;5(10):1275-1281.e2. doi: 10.1016/j.medj.2024.06.007. Epub 2024 Jul 17.

  PMID: 39025065 BACKGROUND

• 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. Date of study termination was 30 June 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 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2020
• First Posted: March 2, 2021
• Study Start: November 8, 2020
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: September 27, 2024
• Results First Posted: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)