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

Primary Purpose

Rett Syndrome

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Trofinetide
Placebo
Sponsored by
ACADIA Pharmaceuticals Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rett Syndrome

Eligibility Criteria

5 Years - 20 Years (Child, Adult)FemaleDoes not accept healthy volunteers

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).

Sites / Locations

  • University of Alabama at Birmingham
  • Translational Gemomics Research Institute (TGen)
  • University of California, San Diego
  • UC Davis MIND Institute
  • Children's Hospital Colorado
  • Children Medical Services
  • Emory Genetics Clinical Trial Center
  • Rush University Children's Hospital
  • Kennedy Krieger Institute - Clinical Trials Unit
  • Boston Children's Hospital Harvard Medical School
  • Gillette Children's Specialty Healthcare
  • Washington University School of Medicine
  • Montefiore Medical Center, Children's Hospital at Montefiore
  • The University of North Carolina at Chapel Hill
  • Cincinnati Children's Hospital Medical Center
  • Cleveland Clinic
  • Children's Hospital of Philadelphia
  • Greenwood Genetic Center
  • Vanderbilt University Medical Center
  • Texas Children's Hospital
  • Seattle Children's

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Drug - Trofinetide

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Rett Syndrome Behaviour Questionnaire (RSBQ) total score - Change from Baseline to Week 12
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.
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.

Secondary Outcome Measures

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 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).
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.
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 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.
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.
Change from Baseline to Week 12 in Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (items 1-24)
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.
Change from Baseline to Week 12 in Impact of Childhood Neurologic Disability Scale (ICND) Total Score
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").
Change from Baseline to Week 12 in Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND)
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").
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.
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.

Full Information

First Posted
November 26, 2019
Last Updated
October 28, 2022
Sponsor
ACADIA Pharmaceuticals Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04181723
Brief Title
Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (LAVENDER™)
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
November 6, 2019 (Actual)
Primary Completion Date
October 28, 2021 (Actual)
Study Completion Date
October 28, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ACADIA Pharmaceuticals Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rett Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
187 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Drug - Trofinetide
Arm Type
Experimental
Arm Description
Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)
Intervention Type
Drug
Intervention Name(s)
Trofinetide
Intervention Description
Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Primary Outcome Measure Information:
Title
Rett Syndrome Behaviour Questionnaire (RSBQ) total score - Change from Baseline to Week 12
Description
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.
Time Frame
12 Weeks Treatment Duration
Title
Clinical Global Impression-Improvement (CGI-I) Score at Week 12
Description
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.
Time Frame
12 Weeks Treatment Duration
Secondary Outcome Measure Information:
Title
Change from Baseline to Week 12 in Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social)
Description
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).
Time Frame
12 Weeks Treatment Duration
Title
Change from Baseline to Week 12 in Rett Syndrome Clinician Rating of Hand Function (RTT-HF)
Description
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.
Time Frame
12 Weeks Treatment Duration
Title
Change from Baseline to Week 12 in Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB)
Description
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.
Time Frame
12 Weeks Treatment Duration
Title
Change from Baseline to Week 12 in Clinical Global Impression-Severity (CGI-S)
Description
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.
Time Frame
12 Weeks Treatment Duration
Title
Change from Baseline to Week 12 in Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (items 1-24)
Description
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.
Time Frame
12 Weeks Treatment Duration
Title
Change from Baseline to Week 12 in Impact of Childhood Neurologic Disability Scale (ICND) Total Score
Description
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").
Time Frame
12 Weeks Treatment Duration
Title
Change from Baseline to Week 12 in Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND)
Description
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").
Time Frame
12 Weeks Treatment Duration
Title
Change from Baseline to Week 12 in Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC)
Description
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.
Time Frame
12 Weeks Treatment Duration
Title
Change from Baseline to Week 12 in Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM)
Description
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.
Time Frame
12 Weeks Treatment Duration

10. Eligibility

Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female subjects 5 to 20 years of age, inclusive, at Screening Body weight ≥12 kg at Screening Can swallow the study medication provided as a liquid solution or can take it by gastrostomy tube Has classic/typical Rett syndrome (RTT) Has a documented disease-causing mutation in the MECP2 gene Has a stable pattern of seizures, or has had no seizures, within 8 weeks of Screening 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. 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 Screening Exclusion Criteria: Has been treated with insulin within 12 weeks of Baseline 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 Has a history of, or current, cerebrovascular disease or brain trauma Has significant, uncorrected visual or uncorrected hearing impairment Has a history of, or current, malignancy 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).
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Translational Gemomics Research Institute (TGen)
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85012
Country
United States
Facility Name
University of California, San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
UC Davis MIND Institute
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80042
Country
United States
Facility Name
Children Medical Services
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Emory Genetics Clinical Trial Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush University Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Kennedy Krieger Institute - Clinical Trials Unit
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Boston Children's Hospital Harvard Medical School
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Gillette Children's Specialty Healthcare
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Montefiore Medical Center, Children's Hospital at Montefiore
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
The University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Greenwood Genetic Center
City
Greenwood
State/Province
South Carolina
ZIP/Postal Code
29646
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Children's
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35149233
Citation
Neul JL, Percy AK, Benke TA, Berry-Kravis EM, Glaze DG, Peters SU, Jones NE, Youakim JM. Design and outcome measures of LAVENDER, a phase 3 study of trofinetide for Rett syndrome. Contemp Clin Trials. 2022 Mar;114:106704. doi: 10.1016/j.cct.2022.106704. Epub 2022 Feb 8.
Results Reference
derived

Learn more about this trial

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

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