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

• ClinicalTrials.gov Identifier: NCT04279314
• Recruitment Status: Active, not recruiting
• First Posted: February 21, 2020
• Last Update Posted: December 1, 2021
• 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 and women with Rett syndrome

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 180 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 40-Week, Open-label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome
• Actual Study Start Date: January 29, 2020
• Estimated Primary Completion Date: October 2022
• Estimated Study Completion Date: October 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Trofinetide	Drug: Trofinetide; Trofinetide solution of 30-60 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)

Outcome Measures

Primary Outcome Measures :

1. Percentage of subjects with treatment-emergent adverse events (TAEs), percentage of subjects with serious adverse events (SAEs), and percentage of subjects withdrawals due to adverse events (AEs) [ Time Frame: 40 Weeks Treatment Duration ]
2. Number of subjects with post-Baseline potentially clinically important changes in ECG [ Time Frame: 40 Weeks Treatment Duration ]
3. Percentage of subjects with post-Baseline potentially clinically important changes in ECG [ Time Frame: 40 Weeks Treatment Duration ]
4. Number of subjects with post-Baseline potentially clinically important changes in vital signs [ Time Frame: 40 Weeks Treatment Duration ]
5. Percentage of subjects with post-Baseline potentially clinically important changes in vital signs [ Time Frame: 40 Weeks Treatment Duration ]
6. Number of subjects with post-Baseline potentially clinically important changes in body weight [ Time Frame: 40 Weeks Treatment Duration ]
7. Percentage of subjects with post-Baseline potentially clinically important changes in body weight [ Time Frame: 40 Weeks Treatment Duration ]
8. Number of subjects with post-Baseline potentially clinically important changes in laboratory parameters [ Time Frame: 40 Weeks Treatment Duration ]
9. Percentage of subjects with post-Baseline potentially clinically important changes in laboratory parameters [ Time Frame: 40 Weeks Treatment Duration ]

Secondary Outcome Measures :

1. Rett Syndrome Behaviour Questionnaire (RSBQ) total score - change from Baseline to Week 40 [ Time Frame: 40 Weeks Treatment Duration ]
   The scale includes 45 items, 39 of them grouped into 8 subscales, whose ratings reflect the severity and frequency of symptoms. Items are rated as "0" (not true), "1" (somewhat or sometimes true), or "2" (very true). The 8 subscales include general mood, breathing problems, hand behavior, face movements, body rocking/expressionless face, night-time behaviors, fear/anxiety, and walking/standing.
2. Clinical Global Impression-Improvement (CGI-I) score at Week 40 [ Time Frame: 40 Weeks Treatment Duration ]
   To rate how much the subject's illness has improved or worsened relative to a baseline state, a 7-point scale is used from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse.
3. Change from Baseline to Week 40 in Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social) [ Time Frame: 40 Weeks Treatment Duration ]
   Standardized screening scale for assessing communication and pre-linguistic skills in young children 12-24 months and can be used with older children with developmental delay. The CSBS-DP includes a suite of three separate measures: The Infant-Toddler Checklist, a follow-up Caregiver Questionnaire and a Behavior Sample. In this study only the Infant-Toddler (CSBS-DP-IT) Checklist will be used. The CSBS-DP-IT Checklist is a 24-item rating scale and each item is scored using a three-level rating of frequency: "not yet", "sometimes" and "often". Three composite scores assessing 7 skill areas can be calculated: 1) Social Composite (including Emotion and Eye Gaze, Communication Rate and Function, and Gestures); 2) Speech Composite (including Sounds and Words); 3) Symbolic Composite (including Understanding and Object Use).
4. Change from Baseline to Week 40 in Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND) [ Time Frame: 40 Weeks Treatment Duration ]
   The scale evaluates the effect of four conditions or health problems on 11 aspects of a child's or family's life as "A lot", "Some", "A little", "Not at all", or "Does not apply". The four conditions or health problems are 1) inattentiveness, impulsivity, or mood, 2) ability to think and remember, 3) neurologic or physical limitations, and 4) epilepsy. The overall quality of life of the subject is also rated by responding to the following: "Please rate your child's overall 'Quality of Life' on the scale below. Choose the number which you feel is best and circle it." The choices range from 1 ("Poor") to 6 ("Excellent").
5. Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Hand Function (RTT-HF) [ Time Frame: 40 Weeks Treatment Duration ]
   Clinical assessment of the subject's ability to use their hands for functional purposes (such as reaching for and grasping objects, self-feeding, or drawing). The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
6. Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB) [ Time Frame: 40 Weeks Treatment Duration ]
   Clinical assessment of the subject's ability to sit, stand, and ambulate (e.g., walking, running, climbing stairs). The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
7. Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC) [ Time Frame: 40 Weeks Treatment Duration ]
   Clinical assessment of the subject's ability to communicate their choices or preferences, which can include the use of nonverbal means such as eye contact or gestures. The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
8. Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM) [ Time Frame: 40 Weeks Treatment Duration ]
   Clinical assessment of the subject's ability to communicate verbally (e.g., words and phrases). The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
9. Change from Baseline to Week 40 in Clinical Global Impression-Severity (CGI-S) [ Time Frame: 40 Weeks Treatment Duration ]
   A 7 point scale that rates the severity of the subject's illness at the time of assessment, relative to the clinician's experience with subjects who have the same diagnosis. A subject is assessed on severity of illness at the time of rating: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; or 7= extremely ill.
10. Change from Baseline to Week 40 in Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (items 1-24) [ Time Frame: 40 Weeks Treatment Duration ]
    The scale is intended to directly address caregiver burden and indirectly assess the significance of treatment effects on function in the context of activities of daily living. Ratings are on a 5-point Likert scale including: 0-never; 1-rarely; 2-sometimes; 3-frequently and 4-nearly always. As in the original Caregiver Burden Inventory, the RTT-CBI has 24 negatively worded items (items 1 through 24) yielding a total score up to 96.
11. Change from Baseline to Week 40 in Impact of Childhood Neurologic Disability Scale (ICND) Total Score [ Time Frame: 40 Weeks Treatment Duration ]
    The scale evaluates the effect of four conditions or health problems on 11 aspects of a child's or family's life as "A lot", "Some", "A little", "Not at all", or "Does not apply". The four conditions or health problems are 1) inattentiveness, impulsivity, or mood, 2) ability to think and remember, 3) neurologic or physical limitations, and 4) epilepsy. The overall quality of life of the subject is also rated by responding to the following: "Please rate your child's overall 'Quality of Life' on the scale below. Choose the number which you feel is best and circle it." The choices range from 1 ("Poor") to 6 ("Excellent").

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 21 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Has completed the Week 12/End-of-treatment visit of the antecedent study, Study ACP-2566-003
2. Met all entry criteria for the antecedent study
3. May benefit from long-term treatment with open-label trofinetide in the judgment of the Investigator
4. Can still swallow the study medication provided as a liquid solution or can take it by gastrostomy tube
5. The subject's caregiver is English-speaking and has sufficient language skills to complete the caregiver assessments
6. 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

Exclusion Criteria:

1. Began treatment with growth hormone during the antecedent study
2. Began treatment with IGF-1 during the antecedent study
3. Began treatment with insulin during the antecedent study
4. 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
5. 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
6. Has a clinically significant abnormality in vital signs at Baseline
7. Has a QTcF interval of >450 ms on the Baseline ECG performed before the first dose of trofinetide is given in the present study
8. Has developed a clinically significant ECG finding during the antecedent study

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, 35223

United States, Arizona

Translational Genomics Research Institute (TGen)

Phoenix, Arizona, United States, 85012

United States, California

University of California, San Diego

La Jolla, California, United States, 92093

UC Davis MIND Institute

Sacramento, California, United States, 95817

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

United States, Florida

Children Medical Services

Tampa, Florida, United States, 33606

United States, Georgia

Emory Genetics Clinical Trial Center

Atlanta, Georgia, United States, 30322

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, Maryland

Kennedy Krieger Institute - Clinical Trials Unit

Baltimore, Maryland, United States, 21205

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

United States, Minnesota

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, United States, 55101

United States, Missouri

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

Saint Louis, Missouri, United States, 63110

United States, New York

Montefiore Medical Center, Children's Hospital at Montefiore

Bronx, New York, United States, 10467

United States, North Carolina

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

Greenwood Genetic Center

Greenwood, South Carolina, United States, 29626

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

Texas Children's Hospital

Houston, Texas, United States, 77030

United States, Washington

Seattle Children's

Seattle, Washington, United States, 98105

Sponsors and Collaborators

ACADIA Pharmaceuticals Inc.

More Information

• Responsible Party: ACADIA Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT04279314
• Other Study ID Numbers: ACP-2566-004
• First Posted: February 21, 2020
• Last Update Posted: December 1, 2021
• Last Verified: November 2021

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