Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (LAVENDER™)
Study Details
Study Description
Brief Summary
To investigate the efficacy of treatment with oral trofinetide versus placebo in females with Rett syndrome
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Drug - Trofinetide Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) |
Drug: Trofinetide
Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
|
| Placebo Comparator: Placebo 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) |
Other: Placebo
Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
|
Outcome Measures
Primary Outcome Measures
- Rett Syndrome Behaviour Questionnaire (RSBQ) total score - Change from Baseline to Week 12 [12 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.
- Clinical Global Impression-Improvement (CGI-I) Score at Week 12 [12 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.
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) [12 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).
- Change from Baseline to Week 12 in Rett Syndrome Clinician Rating of Hand Function (RTT-HF) [12 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.
- Change from Baseline to Week 12 in Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB) [12 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.
- Change from Baseline to Week 12 in Clinical Global Impression-Severity (CGI-S) [12 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.
- Change from Baseline to Week 12 in Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (items 1-24) [12 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.
- Change from Baseline to Week 12 in Impact of Childhood Neurologic Disability Scale (ICND) Total Score [12 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").
- Change from Baseline to Week 12 in Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND) [12 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").
- Change from Baseline to Week 12 in Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC) [12 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.
- Change from Baseline to Week 12 in Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM) [12 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.
Eligibility Criteria
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
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Has a stable pattern of seizures, or has had no seizures, within 8 weeks of Screening
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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
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Has significant, uncorrected visual or uncorrected hearing impairment
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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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35233 |
| 2 | Translational Gemomics Research Institute (TGen) | Phoenix | Arizona | United States | 85012 |
| 3 | University of California, San Diego | La Jolla | California | United States | 92093 |
| 4 | UC Davis MIND Institute | Sacramento | California | United States | 95817 |
| 5 | Children's Hospital Colorado | Aurora | Colorado | United States | 80042 |
| 6 | Children Medical Services | Tampa | Florida | United States | 33606 |
| 7 | Emory Genetics Clinical Trial Center | Atlanta | Georgia | United States | 30322 |
| 8 | Rush University Children's Hospital | Chicago | Illinois | United States | 60612 |
| 9 | Kennedy Krieger Institute - Clinical Trials Unit | Baltimore | Maryland | United States | 21205 |
| 10 | Boston Children's Hospital Harvard Medical School | Boston | Massachusetts | United States | 02115 |
| 11 | Gillette Children's Specialty Healthcare | Saint Paul | Minnesota | United States | 55101 |
| 12 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 13 | Montefiore Medical Center, Children's Hospital at Montefiore | Bronx | New York | United States | 10467 |
| 14 | The University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 15 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 16 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 17 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 18 | Greenwood Genetic Center | Greenwood | South Carolina | United States | 29646 |
| 19 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
| 20 | Texas Children's Hospital | Houston | Texas | United States | 77030 |
| 21 | Seattle Children's | Seattle | Washington | United States | 98105 |
Sponsors and Collaborators
- ACADIA Pharmaceuticals Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ACP-2566-003