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

Rett Syndrome Clinical Trial

— LILAC™  

Official title:

A 40-Week, Open-label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04279314
• Other study ID #: ACP-2566-004
• Status: Completed
• Phase: Phase 3
• Start date: January 29, 2020
• Est. completion date: August 19, 2022

Study information

• Verified date: March 2024
• Source: ACADIA Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: August 19, 2022
• Est. primary completion date: August 19, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 5 Years to 21 Years

Eligibility

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).

Related Conditions & MeSH terms

• Rett Syndrome
• Syndrome

Intervention

Drug:
• Trofinetide
Trofinetide solution of 30-60 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)

Locations

Country	Name	City	State
United States	Emory Genetics Clinical Trial Center	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Kennedy Krieger Institute - Clinical Trials Unit	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Montefiore Medical Center, Children's Hospital at Montefiore	Bronx	New York
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Greenwood Genetic Center	Greenwood	South Carolina
United States	Texas Children's Hospital	Houston	Texas
United States	University of California, San Diego	La Jolla	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Translational Genomics Research Institute (TGen)	Phoenix	Arizona
United States	UC Davis MIND Institute	Sacramento	California
United States	Washington University School of Medicine, St. Louis Children's Hospital	Saint Louis	Missouri
United States	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota
United States	Seattle Children's	Seattle	Washington
United States	Children Medical Services	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
ACADIA Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	40 Weeks Treatment Duration
Primary	Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in ECG	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	40 Weeks Treatment Duration
Primary	Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Vital Signs	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	40 Weeks Treatment Duration
Primary	Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Body Weight	Potentially clinically important changes in body weight were defined in the study protocol as: Weight increase =7% from baseline; Weight decrease =7% from baseline	40 Weeks Treatment Duration
Primary	Subjects (N, %) With Post-baseline Potentially Clinically Important Changes	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	40 Weeks Treatment Duration
Secondary	Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score Change From Baseline to Week 40	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.	40 Weeks Treatment Duration
Secondary	Clinical Global Impression-Improvement (CGI-I) Score at Week 40	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.	40 Weeks Treatment Duration
Secondary	Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social) Change From Baseline to Week 40	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.	40 Weeks Treatment Duration
Secondary	Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND) Change From Baseline to Week 40	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.	40 Weeks Treatment Duration
Secondary	Rett Syndrome Clinician Rating of Hand Function (RTT-HF) Change From Baseline to Week 40	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	40 Weeks Treatment Duration
Secondary	Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB) Change From Baseline to Week 40	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.	40 Weeks Treatment Duration
Secondary	Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC) Change From Baseline to Week 40	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.	40 Weeks Treatment Duration
Secondary	Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM) Change From Baseline to Week 40	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.	40 Weeks Treatment Duration
Secondary	Change From Baseline to Week 40 in Clinical Global Impression-Severity (CGI-S)	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.	40 Weeks Treatment Duration
Secondary	Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (Items 1-24) Change From Baseline to Week 40	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.	40 Weeks Treatment Duration
Secondary	Impact of Childhood Neurologic Disability Scale (ICND) Total Score Change From Baseline to Week 40	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.	40 Weeks Treatment Duration