Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (LAVENDER™)

Rett Syndrome Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04181723
• Other study ID #: ACP-2566-003
• Status: Completed
• Phase: Phase 3
• Start date: November 6, 2019
• Est. completion date: October 28, 2021

Study information

• Verified date: April 2024
• Source: ACADIA Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To investigate the efficacy of treatment with oral trofinetide versus placebo in females with Rett syndrome

Recruitment information / eligibility

• Status: Completed
• Enrollment: 187
• Est. completion date: October 28, 2021
• Est. primary completion date: October 28, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 5 Years to 20 Years

Eligibility

Inclusion Criteria:

1. Female subjects 5 to 20 years of age, inclusive, at Screening

2. Body weight =12 kg at Screening

3. Can swallow the study medication provided as a liquid solution or can take it by gastrostomy tube

4. Has classic/typical Rett syndrome (RTT)

5. Has a documented disease-causing mutation in the MECP2 gene

6. Has a stable pattern of seizures, or has had no seizures, within 8 weeks of Screening

7. Subjects of childbearing potential must abstain from sexual activity for the duration of the study and for at least 30 days thereafter or must agree to use acceptable methods of contraception. Subject must not be pregnant or breastfeeding.

8. The subject's caregiver is English-speaking and has sufficient language skills to complete the caregiver assessments

9. 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 Screening

Exclusion Criteria:

1. Has been treated with insulin within 12 weeks of Baseline

2. 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

3. Has a history of, or current, cerebrovascular disease or brain trauma

4. Has significant, uncorrected visual or uncorrected hearing impairment

5. Has a history of, or current, malignancy

6. Has a known history or symptoms of long QT syndrome

Additional inclusion/exclusion criteria apply. Patients will be evaluated at screening 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 pre-specified entry criteria).

Related Conditions & MeSH terms

• Rett Syndrome
• Syndrome

Intervention

Drug:
• Trofinetide
Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks

Other:
• Placebo
Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks

Locations

Country	Name	City	State
United States	Emory Genetics Clinical Trial Center	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Kennedy Krieger Institute - Clinical Trials Unit	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital Harvard Medical School	Boston	Massachusetts
United States	Montefiore Medical Center, Children's Hospital at Montefiore	Bronx	New York
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Rush University Children's Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Greenwood Genetic Center	Greenwood	South Carolina
United States	Texas Children's Hospital	Houston	Texas
United States	University of California, San Diego	La Jolla	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Translational Gemomics Research Institute (TGen)	Phoenix	Arizona
United States	UC Davis MIND Institute	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota
United States	Seattle Children's	Seattle	Washington
United States	Children Medical Services	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
ACADIA Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score - Change From Baseline to Week 12	The RSBQ is a 45-item caregiver-completed rating scale that 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 are general mood, breathing problems, hand behavior, face movements, body rocking/expressionless face, night-time behaviors, fear/anxiety, and walking/standing. Scores for item 31 are reversed in the calculation of the total score. The total score ranges from 0 to 90 and is calculated as the sum of the item scores. Higher scores mean worse behaviour.	Baseline and Week 12
Primary	Clinical Global Impression-Improvement (CGI-I) Score at Week 12	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.	12 Weeks Treatment Duration
Secondary	Change From Baseline to Week 12 in Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social)	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 was 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". The CSBS-DP-IT Social Composite score the range was 0 to 26 and a higher score represented a worse outcome. Three composite scores can be calculated: 1) Social Composite; 2) Speech Composite; 3) Symbolic Composite.	12 Weeks Treatment Duration
Secondary	Change From Baseline to Week 12 in Impact of Childhood Neurologic Disability Scale (ICND) Total Score	The Impact of Childhood Neurologic Disability (ICND) 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 ICND score the range of 0 to 132 and a higher score represents a worse outcome.	12 Weeks Treatment Duration
Secondary	Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Hand Function (RTT-HF)	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.	12 Weeks Treatment Duration
Secondary	Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB)	Clinical assessment of the subject's ability to sit, stand, and ambulate (e.g., walking, running, and climbing stairs). The assessment was made on an 8-point Likert scale (0 to 7), with 0 denoting normal functioning and 7 as the most severe impairment.	12 Weeks Treatment Duration
Secondary	Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC)	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.	12 Weeks Treatment Duration
Secondary	Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM)	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.	12 Weeks Treatment Duration
Secondary	Change From Baseline to Week 12 in Clinical Global Impression-Severity (CGI-S)	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.	12 Weeks Treatment Duration
Secondary	Change From Baseline to Week 12 in Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (Items 1-24)	The Rett Syndrome Caregiver Burden Inventory (RTT-CBI) 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. The RTT-CBI the range is 0 to 96 and a higher score represents a worse outcome.	12 Weeks Treatment Duration
Secondary	Change From Baseline to Week 12 in Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND)	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").	12 Weeks Treatment Duration