A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- ACADIA Pharmaceuticals Inc.
- Enrollment
- 187
- Locations
- 21
- Primary Endpoint
- Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score - Change From Baseline to Week 12
Study Overview
Brief Summary
To investigate the efficacy of treatment with oral trofinetide versus placebo in females with Rett syndrome
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 5 Years to 20 Years (Child, Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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).
Arms & Interventions
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)
Intervention: Trofinetide (Drug)
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)
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score - Change From Baseline to Week 12
Time Frame: Baseline and 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.
Clinical Global Impression-Improvement (CGI-I) Score at Week 12
Time Frame: 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 Outcomes
- 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 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 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)
- Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM)(12 Weeks Treatment Duration)
- Change From Baseline to Week 12 in Clinical Global Impression-Severity (CGI-S)(12 Weeks Treatment Duration)
- 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)
- Change From Baseline to Week 12 in Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (Items 1-24)(12 Weeks Treatment Duration)