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Trial · Interventional

CompletedPhase 3Results postedRegistry data

Open-Label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome

Short name LILAC™

NCTNCT04279314 (opens ClinicalTrials.gov in a new tab)Other idACP-2566-004
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
154 participants (actual)
Sponsor
ACADIA Pharmaceuticals Inc. · Industry
Design
Allocation not applicable · Open label (no masking)
Countries
1 country

United States

Start
29 Jan 2020
Primary completion
19 Aug 2022
Completion
19 Aug 2022
First posted
21 Feb 2020
Last update posted
11 Apr 2024
Conditions
Rett Syndrome

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2020202120222023
  1. Ph 3

    LILAC™

    NCT04279314

    29 Jan 2020 to 19 Aug 2022

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

To investigate the safety and tolerability of long-term treatment with oral trofinetide in girls and women with Rett syndrome

Interventions

  • TrofinetideDrug

Arms1

  • Experimental

    Trofinetide

Primary outcomes5

Outcomes the sponsor listed as primary.

  1. Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs), Percentage of Subjects With Serious Adverse Events (SAEs), and Percentage of Subjects With Withdrawals Due to AEs

    Time frame · 40 Weeks Treatment Duration

    Registry description

    Percentage of subjects with treatment-emergent adverse events (TEAEs), percentage of subjects with serious adverse events (SAEs), and percentage of subjects with withdrawals due to AEs

  2. Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in ECG

    Time frame · 40 Weeks Treatment Duration

    Registry description

    Potentially clinically important ECG changes were defined in the study protocol as absolute QTcF interval \>500 ms or QTcF interval change from the baseline value of previous study ACP-2566-003 of \>60 ms

  3. Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Vital Signs

    Time frame · 40 Weeks Treatment Duration

    Registry description

    Potentially clinically important changes in vital signs were defined in the study protocol as: systolic blood pressure (SBP) ≥180 mmHg and increased ≥20 mmHg from baseline; SBP ≤90 mmHg and decreased ≥20 mmHg from baseline; diastolic blood pressure (DBP) ≥ 105 mmHg and increased ≥15 mmHg from baseline; DBP ≤50 mmHg and decreased ≥15 mmHg from baseline; Pulse ≥120 bpm and increased ≥15 bpm from baseline; Pulse ≤50 bpm and decreased ≥15 bpm from baseline

  4. Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Body Weight

    Time frame · 40 Weeks Treatment Duration

    Registry description

    Potentially clinically important changes in body weight were defined in the study protocol as: Weight increase ≥7% from baseline; Weight decrease ≥7% from baseline

  5. Subjects (N, %) With Post-baseline Potentially Clinically Important Changes

    Time frame · 40 Weeks Treatment Duration

    Registry description

    Potentially clinically important changes in laboratory parameters were defined in the study protocol as: Sodium ≤125 mmol/L; Sodium ≥155 mmol/L; Potassium ≤3.0 mmol/L; Potassium ≥5.5 mmol/L; Chloride ≤85 mmol/L; Chloride ≥120 mmol/L; Calcium \<2.0 mmol/L; Calcium \>2.0 mmol/L; Blood urea nitrogen ≥10.71 mmol/L; Creatinine \>1.5 x upper limit of normal (ULN); Uric acid ≥505.75 μmol/L; Lactate dehydrogenase ≥3 x ULN; Glucose ≤2.48 mmol/L; Glucose ≥11 mmol/L; Albumin ≤26 g/L; Albumin ≥60 g/L; Protein ≤50 g/L; Protein ≥100 g/L; Alanine aminotransferase ≥3 x ULN; Aspartate aminotransferase ≥3 x ULN; Gamma glutamyl transpeptidase ≥3 x ULN; Alkaline phosphatase ≥3 x ULN; Bilirubin ≥1.5 x ULN

Secondary outcomes(11)

  1. Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score Change From Baseline to Week 40

    Time frame · 40 Weeks Treatment Duration

    Registry description

    The RSBQ is a 45-item caregiver-completed rating scalescale 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.

  2. Clinical Global Impression-Improvement (CGI-I) Score at Week 40

    Time frame · 40 Weeks Treatment Duration

    Registry 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. Higher CGI-I scores denote more severe illness and less improvement in the illness.

  3. Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social) Change From Baseline to Week 40

    Time frame · 40 Weeks Treatment Duration

    Registry description

    Scale to assess communication and pre-linguistic skills in children 12-24 months (or older children with developmental delay). The Checklist consists of 24 questions ranging from 0 to 4 points within each of 7 Clusters. 0 points are given for"Not Yet", 1 point for "Sometimes", or 2 points for "Often". For items describing a series of numbers or ranges, 0 points are given for "None" and 1 to 4 points for items containing numbered choices. The Social Composite score is one of 3 composite scores. It comprises 13 items in skill areas "Emotion and Eye Gaze" (items 1 to 4), "Communication" (items 5 to 8), and "Gestures" (items 9 to 13). The Social Composite raw score (items 1 to 13), ranging from 0 to 26, is calculated as the sum of the item scores. Higher Social Composite raw scores indicate better social communication development.

  4. Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND) Change From Baseline to Week 40

    Time frame · 40 Weeks Treatment Duration

    Registry description

    The overall quality of life score rating of the ICND ranges from 1 ("Poor") to 6 ("Excellent"); lower overall quality of life scores indicate lower quality of life.

  5. Rett Syndrome Clinician Rating of Hand Function (RTT-HF) Change From Baseline to Week 40

    Time frame · 40 Weeks Treatment Duration

    Registry description

    The RTT-HF is a clinician completed clinical assessment of the subject's ability to use her hands for functional purposes. The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment

  6. Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB) Change From Baseline to Week 40

    Time frame · 40 Weeks Treatment Duration

    Registry description

    The RTT-AMB is a clinician completed clinical assessment of the subject's ability to sit, stand, and ambulate. The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.

  7. Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC) Change From Baseline to Week 40

    Time frame · 40 Weeks Treatment Duration

    Registry description

    The RTT-COMC is a clinician completed clinical assessment of the subject's ability to communicate her 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.

  8. Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM) Change From Baseline to Week 40

    Time frame · 40 Weeks Treatment Duration

    Registry description

    The RTT-VCOM is a clinician completed clinical assessment of the subject's ability to communicate verbally. The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.

  9. Change From Baseline to Week 40 in Clinical Global Impression-Severity (CGI-S)

    Time frame · 40 Weeks Treatment Duration

    Registry description

    The CGI-S is a 7-point scale that requires the clinician to rate 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. Considering total clinical experience, 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. Higher CGI-S scores denote more severe illness and less improvement in the illness.

  10. Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (Items 1-24) Change From Baseline to Week 40

    Time frame · 40 Weeks Treatment Duration

    Registry description

    The RTT-CBI consists of 24 negatively worded items (Items 1 through 24). Frequency ratings are on a 5-point Likert scale including: 0-never; 1-rarely; 2-sometimes; 3-frequently and 4-nearly always. The RTT-CBI also includes 2 positively worded items (items 25 and 26) that comprise the Optimism Index; this index will not be used for analysis. The total score ranging from 0 to 96 is calculated as the sum of the scores for Items 1-24.Higher scores signify higher caregiver burden.

  11. Impact of Childhood Neurologic Disability Scale (ICND) Total Score Change From Baseline to Week 40

    Time frame · 40 Weeks Treatment Duration

    Registry description

    The ICND scale evaluates the effect of 4 health problems on 11 aspects of the child's or the family's life scored 0 ("Not at all"), 1 ("A little"), 2 ("Some"), 3 ("A lot"), or "Does not apply". The 4 health problems are 1) inattentiveness, impulsivity, or mood, 2) ability to think and remember, 3) neurologic or physical limitations, and 4) epilepsy. For each health problem, the score is calculated as the sum of the item scores. The ICND total score will be calculated as the sum of the average of each problem score multiplied by 11. The ICND total score ranges from 0 to 132. Higher ICND total scores indicate worse health problems. The ICND total score does not include the Overall Quality of Life Rating.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· 40 Weeks Treatment Duration

Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs), Percentage of Subjects With Serious Adverse Events (SAEs), and Percentage of Subjects With Withdrawals Due to AEs

GroupValue (Participants)
Trofinetide132
Primary outcomeCount of participants· 40 Weeks Treatment Duration

Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in ECG

GroupValue (Participants)
Trofinetide2
Primary outcomeCount of participants· 40 Weeks Treatment Duration

Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Vital Signs

GroupValue (Participants)
Trofinetide0
Primary outcomeCount of participants· 40 Weeks Treatment Duration

Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Body Weight

GroupValue (Participants)
Trofinetide44
Primary outcomeCount of participants· 40 Weeks Treatment Duration

Subjects (N, %) With Post-baseline Potentially Clinically Important Changes

GroupValue (Participants)
Trofinetide0
Secondary and other outcome results(3)
Secondary outcomeMean· 40 Weeks Treatment Duration

Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score Change From Baseline to Week 40

GroupValue (score on a scale)Spread
Trofinetide-2.91.17
Secondary outcomeMean· 40 Weeks Treatment Duration

Clinical Global Impression-Improvement (CGI-I) Score at Week 40

GroupValue (score on a scale)Spread
Placebo/Trofinetide3.20.14
Trofinetide/Trofinetide3.10.11
Secondary outcomeMean· 40 Weeks Treatment Duration

Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social) Change From Baseline to Week 40

GroupValue (score on a scale)Spread
Trofinetide0.50.26

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
TrofinetideAll subjects enrolled and treated with trofinetide0 / 15419 / 154114 / 154

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2024

8 results

Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study.

Percy et al. 2024Med (New York, N.Y.)cited by 25

PMID 38917793DOI 10.1016/j.medj.2024.05.018PUB-38917793

Full text at the publisher8 results
Publisher pageSee results (8)

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedParent 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

Eligibility

Who could join, as posted.

Sex
Female
Age
from 5 Years up to 21 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. Has completed the Week 12/End-of-treatment visit of the antecedent study, Study ACP-2566-003 2. Met all entry criteria for the antecedent study 3. May benefit from long-term treatment with open-label trofinetide in the judgment of the Investigator 4. Can still swallow the study medication provided as a liquid solution or can take it by gastrostomy tube 5. The subject's caregiver is English-speaking and has sufficient language skills to complete the caregiver assessments 6. 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 Baseline Exclusion Criteria: 1. Began treatment with growth hormone during the antecedent study 2. Began treatment with IGF-1 during the antecedent study 3. Began treatment with insulin during the antecedent study 4. Has developed a 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 5. Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study due to AEs, medical condition, or noncompliance with investigational product or study procedures in the antecedent study 6. Has a clinically significant abnormality in vital signs at Baseline 7. Has a QTcF interval of \>450 ms on the Baseline ECG performed before the first dose of trofinetide is given in the present study 8. Has developed a clinically significant ECG finding during the antecedent study Additional inclusion/exclusion criteria apply. Patients will be evaluated at baseline 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 prespecified entry criteria).

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