Trial Outcomes & Findings for Open-Label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (NCT NCT04279314)

NCT ID: NCT04279314

Last Updated: 2024-04-11

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 154 participants
• Primary outcome timeframe: 40 Weeks Treatment Duration
• Results posted on: 2024-04-11

Participant Flow

Participant milestones

Measure	Trofinetide Trofinetide: Trofinetide solution of 30-60 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)
Overall Study STARTED	154
Overall Study COMPLETED	84
Overall Study NOT COMPLETED	70

Reasons for withdrawal

Measure	Trofinetide Trofinetide: Trofinetide solution of 30-60 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)
Overall Study Adverse Event	55
Overall Study Withdrawal by Subject	5
Overall Study Lack of Efficacy	5
Overall Study Protocol Violation	3
Overall Study Other (not COVID-19 related)	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide
Age, Continuous	11.0 years STANDARD_DEVIATION 4.55 • n=5 Participants
Sex: Female, Male Female	154 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	143 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants
Height	128.60 cm STANDARD_DEVIATION 1.229 • n=5 Participants
Weight	29.28 kg STANDARD_DEVIATION 0.869 • n=5 Participants
Body Mass Index	17.03 kg/m2 STANDARD_DEVIATION 0.285 • n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
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 TEAEs	132 Participants	—
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 SAEs	19 Participants	—
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 withdrawals due to AEs	48 Participants	—

PRIMARY outcome

Timeframe: 40 Weeks Treatment Duration

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

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in ECG	2 Participants	—

PRIMARY outcome

Timeframe: 40 Weeks Treatment Duration

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

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Vital Signs SBP ≥180 mmHg and increased ≥20 mmHg from baseline	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Vital Signs SBP ≤90 mmHg and decreased ≥20 mmHg from baseline	11 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Vital Signs DBP ≥ 105 mmHg and increased ≥15 mmHg from baseline	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Vital Signs DBP ≤50 mmHg and decreased ≥15 mmHg from baseline	13 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Vital Signs Pulse ≥120 bpm and increased ≥15 bpm from baseline	14 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Vital Signs Pulse ≤50 bpm and decreased ≥15 bpm from baseline	0 Participants	—

PRIMARY outcome

Timeframe: 40 Weeks Treatment Duration

Potentially clinically important changes in body weight were defined in the study protocol as:

Weight increase ≥7% from baseline; Weight decrease ≥7% from baseline

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Body Weight Weight increase ≥7% from baseline	44 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in Body Weight Weight decrease ≥7% from baseline	20 Participants	—

PRIMARY outcome

Timeframe: 40 Weeks Treatment Duration

Population: Subjects with at least 1 post-baseline value for the given parameter (n=151 for all parameters, except LDH (n=150) and AST (=150)

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

Outcome measures

Measure	Trofinetide n=151 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Sodium ≤125 mmol/L	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Sodium ≥155 mmol/L	1 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Potassium ≤3.0 mmol/L	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Potassium ≥5.5 mmol/L	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Chloride ≤85 mmol/L	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Chloride ≥120 mmol/L	1 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Calcium <2.0 mmol/L	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Calcium >2.0 mmol/L	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes BUN ≥10.71 mmol/L	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Creatinine >1.5 x ULN	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Uric acid ≥505.75 μmol/L	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Lactate dehydrogenase ≥3× ULN	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Glucose ≤2.48 mmol/L	4 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Glucose ≥11 mmol/L	1 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Albumin ≤26 g/L	2 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Albumin ≥60 g/L	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Protein ≤50 g/L	1 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Protein ≥100 g/L	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes ALT ≥3× ULN	14 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes AST ≥3× ULN	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes GGT ≥3× ULN	4 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes ALP ≥3× ULN	0 Participants	—
Subjects (N, %) With Post-baseline Potentially Clinically Important Changes Bilirubin ≥1.5× ULN	0 Participants	—

SECONDARY outcome

Timeframe: 40 Weeks Treatment Duration

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.

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score Change From Baseline to Week 40	-2.9 score on a scale Standard Error 1.17	—

SECONDARY outcome

Timeframe: 40 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. Higher CGI-I scores denote more severe illness and less improvement in the illness.

Outcome measures

Measure	Trofinetide n=85 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide n=69 Participants Subject received trofinetidein the parent study and trofinetide in the current study
Clinical Global Impression-Improvement (CGI-I) Score at Week 40	3.2 score on a scale Standard Error 0.14	3.1 score on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: 40 Weeks Treatment Duration

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.

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social) Change From Baseline to Week 40	0.5 score on a scale Standard Error 0.26	—

SECONDARY outcome

Timeframe: 40 Weeks Treatment Duration

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.

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND) Change From Baseline to Week 40	0.2 score on a scale Standard Error 0.09	—

SECONDARY outcome

Timeframe: 40 Weeks Treatment Duration

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

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Rett Syndrome Clinician Rating of Hand Function (RTT-HF) Change From Baseline to Week 40	-0.1 score on a scale Standard Error 0.09	—

SECONDARY outcome

Timeframe: 40 Weeks Treatment Duration

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.

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB) Change From Baseline to Week 40	-0.2 score on a scale Standard Error 0.09	—

SECONDARY outcome

Timeframe: 40 Weeks Treatment Duration

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.

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC) Change From Baseline to Week 40	-0.4 score on a scale Standard Error 0.13	—

SECONDARY outcome

Timeframe: 40 Weeks Treatment Duration

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.

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM) Change From Baseline to Week 40	-0.2 score on a scale Standard Error 0.07	—

SECONDARY outcome

Timeframe: 40 Weeks Treatment Duration

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.

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Change From Baseline to Week 40 in Clinical Global Impression-Severity (CGI-S)	-0.1 score on a scale Standard Error 0.04	—

SECONDARY outcome

Timeframe: 40 Weeks Treatment Duration

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.

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (Items 1-24) Change From Baseline to Week 40	-1.9 score on a scale Standard Error 1.05	—

SECONDARY outcome

Timeframe: 40 Weeks Treatment Duration

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.

Outcome measures

Measure	Trofinetide n=154 Participants All subjects enrolled and treated with trofinetide	Trofinetide/Trofinetide Subject received trofinetidein the parent study and trofinetide in the current study
Impact of Childhood Neurologic Disability Scale (ICND) Total Score Change From Baseline to Week 40	-5.8 score on a scale Standard Error 3.91	—

Adverse Events

Trofinetide

Serious events: 19 serious events

Other events: 114 other events

Deaths: 0 deaths

Serious adverse events

Measure	Trofinetide n=154 participants at risk All subjects enrolled and treated with trofinetide
Blood and lymphatic system disorders Anaemia	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Gastrointestinal disorders Ileus	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
General disorders Pyrexia	1.3% 2/154 • Number of events 2 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Pneumonia	2.6% 4/154 • Number of events 6 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Rhinovirus infection	1.3% 2/154 • Number of events 2 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Viral infection	1.3% 2/154 • Number of events 2 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations COVID-19	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations COVID-19 pneumonia	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Device related infection	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Enterovirus infection	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Escherichia sepsis	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Gastroenteritis	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Gastroenteritis viral	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Parainfluenzae virus infection	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Peritoneal abscess	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Peritonitis	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Pyelonephritis	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Streptococcal sepsis	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Urinary tract infection	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Urinary tract infection pseudomonal	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Vaginal abscess	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Metabolism and nutrition disorders Dehydration	1.9% 3/154 • Number of events 3 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Nervous system disorders Seizure	3.2% 5/154 • Number of events 6 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Nervous system disorders Status epilepticus	1.3% 2/154 • Number of events 2 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Reproductive system and breast disorders Vaginal discharge	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.3% 2/154 • Number of events 3 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Respiratory, thoracic and mediastinal disorders Aspiration	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.65% 1/154 • Number of events 1 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.65% 1/154 • Number of events 2 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)

Other adverse events

Measure	Trofinetide n=154 participants at risk All subjects enrolled and treated with trofinetide
Gastrointestinal disorders Diarrhoea	59.1% 91/154 • Number of events 129 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Gastrointestinal disorders Vomiting	25.3% 39/154 • Number of events 58 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
General disorders Pyrexia	7.1% 11/154 • Number of events 14 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations COVID-19	10.4% 16/154 • Number of events 16 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Upper respiratory tract infection	7.8% 12/154 • Number of events 14 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Infections and infestations Urinary tract infection	5.8% 9/154 • Number of events 14 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Investigations Weight decreased	5.8% 9/154 • Number of events 9 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Metabolism and nutrition disorders Decreased appetite	6.5% 10/154 • Number of events 11 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)
Nervous system disorders Seizure	6.5% 10/154 • Number of events 14 • 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period)

Additional Information

Sr. Dir. Medical Information and Medical Communications

ACADIA Pharmaceuticals Inc.

Phone: +1-858-261

Email: medicalinformation@acadia-pharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee Investigator may publish the study results, relative to his/her own patients, only after review, comment and approval by the sponsor. No publication of confidential information shall be made without the sponsor's prior written consent. At least 60 days prior to submitting a manuscript or prior to any public presentation, a copy of the manuscript or presentation will be provided to the sponsor for review and comment. The sponsor has 60 days to review and comment.
• Publication restrictions are in place

Restriction type: OTHER