History of Changes for Study: NCT04279314

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

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Study Record Versions

Version	Submitted Date	Changes
1	February 19, 2020	None (earliest Version on record)
2	February 24, 2020	Contacts/Locations and Study Status
3	March 4, 2020	Study Status and Contacts/Locations
4	April 16, 2020	Study Status and Contacts/Locations
5	April 28, 2020	Contacts/Locations and Study Status
6	May 18, 2020	Study Status and Contacts/Locations
7	July 10, 2020	Study Status and Eligibility
8	October 30, 2020	Recruitment Status, Study Status, Contacts/Locations and Eligibility
9	February 2, 2021	Study Status and Contacts/Locations
10	March 24, 2021	Outcome Measures, Study Status and Contacts/Locations
11	April 30, 2021	Study Status and Contacts/Locations
12	May 24, 2021	Study Status and Contacts/Locations
13	June 28, 2021	Study Status and Contacts/Locations
14	September 2, 2021	Study Status and Contacts/Locations
15	September 17, 2021	Contacts/Locations and Study Status
16	November 22, 2021	Study Status and Contacts/Locations
17	November 29, 2021	Recruitment Status and Study Status
18	September 7, 2022	Study Status
19	September 21, 2022	Recruitment Status, Study Status and Study Design
20	March 14, 2024	Study Status, Outcome Measures, Document Section and Results

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	ACP-2566-004
Brief Title:	Open-Label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (LILAC™)
Official Title:	A 40-Week, Open-label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome
Secondary IDs:

Study Status


Record Verification:	February 2021
Overall Status:	Enrolling by invitation
Study Start:	January 29, 2020
Primary Completion:	October 2022 [Anticipated]
Study Completion:	October 2022 [Anticipated]

First Submitted:	February 19, 2020
First Submitted that Met QC Criteria:	February 19, 2020
First Posted:	February 21, 2020 [Actual]

Last Update Submitted that Met QC Criteria:	February 2, 2021
Last Update Posted:	February 4, 2021 [Actual]

Sponsor/Collaborators


Sponsor:	ACADIA Pharmaceuticals Inc.
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	No

Study Description


Brief Summary:	To investigate the safety and tolerability of long-term treatment with oral trofinetide in girls and women with Rett syndrome
Detailed Description:

Conditions


Conditions:	Rett Syndrome
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Single Group Assignment
Number of Arms:	1
Masking:	None (Open Label)
Allocation:	N/A
Enrollment:	180 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
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.	Safety and tolerability of long-term treatment with oral trofinetide [ Time Frame: 40 Weeks Treatment Duration ] Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), withdrawals due to AEs, potentially clinically important changes in other safety assessments
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


Minimum Age:	5 Years
Maximum Age:	21 Years
Sex:	Female
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: 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 Exclusion Criteria: 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 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/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
	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 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, Pennsylvania
	Children's Hospital of Philadelphia Philadelphia, Pennsylvania, United States, 19104
	United States, Texas
	Texas Children's Hospital Houston, Texas, United States, 77030

IPDSharing


Plan to Share IPD:	No

References


Citations:
Links:
Available IPD/Information: