Clinical trial NCT04181723: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rett Syndrome
Lead sponsor: ACADIA Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2019-11-29
Enrollment: 187
Sex: FEMALE
Minimum age (years): 5
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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).

Primary outcomes:
measure: Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score - Change From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Clinical Global Impression-Improvement (CGI-I) Score at Week 12
timeFrame: 12 Weeks Treatment Duration
Secondary outcomes:
measure: Change From Baseline to Week 12 in Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social)
timeFrame: 12 Weeks Treatment Duration
measure: Change From Baseline to Week 12 in Impact of Childhood Neurologic Disability Scale (ICND) Total Score
timeFrame: 12 Weeks Treatment Duration
measure: Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Hand Function (RTT-HF)
timeFrame: 12 Weeks Treatment Duration
measure: Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB)
timeFrame: 12 Weeks Treatment Duration
measure: Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC)
timeFrame: 12 Weeks Treatment Duration
measure: Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM)
timeFrame: 12 Weeks Treatment Duration
measure: Change From Baseline to Week 12 in Clinical Global Impression-Severity (CGI-S)
timeFrame: 12 Weeks Treatment Duration
measure: Change From Baseline to Week 12 in Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (Items 1-24)
timeFrame: 12 Weeks Treatment Duration
measure: Change From Baseline to Week 12 in Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND)
timeFrame: 12 Weeks Treatment Duration
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Translational Gemomics Research Institute (TGen)
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Sacramento
country: United States
facility: UC Davis MIND Institute
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Tampa
country: United States
facility: Children Medical Services
state: Florida
city: Atlanta
country: United States
facility: Emory Genetics Clinical Trial Center
state: Georgia
city: Chicago
country: United States
facility: Rush University Children's Hospital
state: Illinois
city: Baltimore
country: United States
facility: Kennedy Krieger Institute - Clinical Trials Unit
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital Harvard Medical School
state: Massachusetts
city: Saint Paul
country: United States
facility: Gillette Children's Specialty Healthcare
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center, Children's Hospital at Montefiore
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Greenwood
country: United States
facility: Greenwood Genetic Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
Study officials:
References:
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.