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

NCT04181723 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ACP-2566-003
• Study Type: interventional
• Target: 187
• Locations: 1 country
• Sites: 21

Brief Summary

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

Conditions

Rett Syndrome

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (9)

• 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

• Change From Baseline to Week 12 in Impact of Childhood Neurologic Disability Scale (ICND) Total Score

  12 Weeks Treatment Duration

• Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Hand Function (RTT-HF)

  12 Weeks Treatment Duration

• Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB)

  12 Weeks Treatment Duration

• Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC)

  12 Weeks Treatment Duration

Study Arms (2)

Drug - Trofinetide

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Trofinetide DRUG

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

Drug - Trofinetide

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 5 Years - 20 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ACADIA Pharmaceuticals Inc.: lead

Study Sites (21)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Translational Gemomics Research Institute (TGen)

Phoenix, Arizona, 85012, United States

Location

University of California, San Diego

La Jolla, California, 92093, United States

Location

UC Davis MIND Institute

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80042, United States

Location

Children Medical Services

Tampa, Florida, 33606, United States

Location

Emory Genetics Clinical Trial Center

Atlanta, Georgia, 30322, United States

Location

Rush University Children's Hospital

Chicago, Illinois, 60612, United States

Location

Kennedy Krieger Institute - Clinical Trials Unit

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital Harvard Medical School

Boston, Massachusetts, 02115, United States

Location

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, 55101, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Montefiore Medical Center, Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Greenwood Genetic Center

Greenwood, South Carolina, 29646, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's

Seattle, Washington, 98105, United States

Location

Related Publications (4)

• Darwish M, Passarell J, Youakim JM, Bradley H, Bishop KM. Exposure-Response Efficacy Modeling to Support Trofinetide Dosing in Individuals with Rett Syndrome. Adv Ther. 2024 Apr;41(4):1462-1480. doi: 10.1007/s12325-024-02796-y. Epub 2024 Feb 16.

  PMID: 38363467 DERIVED

• Parent H, Ferranti A, Niswender C. Trofinetide: a pioneering treatment for Rett syndrome. Trends Pharmacol Sci. 2023 Oct;44(10):740-741. doi: 10.1016/j.tips.2023.06.008. Epub 2023 Jul 16.

  PMID: 37460385 DERIVED

• Neul JL, Percy AK, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, Lin T, Stankovic S, Bishop KM, Youakim JM. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nat Med. 2023 Jun;29(6):1468-1475. doi: 10.1038/s41591-023-02398-1. Epub 2023 Jun 8.

  PMID: 37291210 DERIVED

• 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.

  PMID: 35149233 DERIVED

MeSH Terms

Conditions

Rett Syndrome

Interventions

trofinetide

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Results Point of Contact

• Title: Study Director
• Organization: Acadia Pharmaceuticals Inc.

medicalinformation@acadia-pharm.com

844-422-2342

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2019
• First Posted: November 29, 2019
• Study Start: November 6, 2019
• Primary Completion: October 28, 2021
• Study Completion: October 28, 2021
• Last Updated: April 8, 2024
• Results First Posted: April 8, 2024

Record last verified: 2024-04

Locations

US (21)