A Phase 3 interventional study of Trofinetide in Rett Syndrome, sponsored by ACADIA Pharmaceuticals Inc.. Completed at 21 sites in United States. Open to female participants aged 5 Years to 21 Years. Per ClinicalTrials.gov, last updated 2024-04-11.
Sponsored by ACADIA Pharmaceuticals Inc. · Phase 3, Interventional, and Treatment
To investigate the safety and tolerability of long-term treatment with oral trofinetide in girls and women with Rett syndrome
98 studies on the registry are indexed under Rett Syndrome; 20 are open to participants now.
This study's enrollment of 154 is above the median of 30 across 64 interventional studies indexed under Rett Syndrome.
Browse Rett Syndrome studies →ACADIA Pharmaceuticals Inc. is the lead sponsor of 41 studies on the registry; 5 are open to participants now.
Of its 25 completed or terminated interventional studies of FDA-regulated products, 23 (92%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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).
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)
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
Time frame: 40 Weeks Treatment Duration
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
Time frame: 40 Weeks Treatment Duration
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
Time frame: 40 Weeks Treatment Duration
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
Time frame: 40 Weeks Treatment Duration
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
Time frame: 40 Weeks Treatment Duration
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.
Time frame: 40 Weeks Treatment Duration
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.
Time frame: 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
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.
Time frame: 40 Weeks Treatment Duration
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.
Time frame: 40 Weeks Treatment Duration
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
Time frame: 40 Weeks Treatment Duration
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.
Time frame: 40 Weeks Treatment Duration
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.
Time frame: 40 Weeks Treatment Duration
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.
Time frame: 40 Weeks Treatment Duration
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.
Time frame: 40 Weeks Treatment Duration
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.
Time frame: 40 Weeks Treatment Duration
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.
Time frame: 40 Weeks Treatment Duration
| Milestone | Trofinetide |
|---|---|
| Started | 154 |
| Completed | 84 |
| Not completed | 70 |
| Withdrew: Adverse event | 55 |
| Withdrew: Withdrawal by subject | 5 |
| Withdrew: Lack of efficacy | 5 |
| Withdrew: Protocol violation | 3 |
| Withdrew: Other (not covid-19 related) | 2 |
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
| Participants | Trofinetide |
|---|---|
| Percentage of subjects with TEAEs | 132 |
| percentage of subjects with SAEs | 19 |
| Percentage of subjects withdrawals due to AEs | 48 |
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
| Participants | Trofinetide |
|---|---|
| Subjects (N, %) With Post-baseline Potentially Clinically Important Changes in ECG | 2 |
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
| Participants | Trofinetide |
|---|---|
| SBP ≥180 mmHg and increased ≥20 mmHg from baseline | 0 |
| SBP ≤90 mmHg and decreased ≥20 mmHg from baseline | 11 |
| DBP ≥ 105 mmHg and increased ≥15 mmHg from baseline | 0 |
| DBP ≤50 mmHg and decreased ≥15 mmHg from baseline | 13 |
| Pulse ≥120 bpm and increased ≥15 bpm from baseline | 14 |
| Pulse ≤50 bpm and decreased ≥15 bpm from baseline | 0 |
Potentially clinically important changes in body weight were defined in the study protocol as: Weight increase ≥7% from baseline; Weight decrease ≥7% from baseline
| Participants | Trofinetide |
|---|---|
| Weight increase ≥7% from baseline | 44 |
| Weight decrease ≥7% from baseline | 20 |
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
| Participants | Trofinetide |
|---|---|
| Sodium ≤125 mmol/L | 0 |
| Sodium ≥155 mmol/L | 1 |
| Potassium ≤3.0 mmol/L | 0 |
| Potassium ≥5.5 mmol/L | 0 |
| Chloride ≤85 mmol/L | 0 |
| Chloride ≥120 mmol/L | 1 |
| Calcium <2.0 mmol/L | 0 |
| Calcium >2.0 mmol/L | 0 |
| BUN ≥10.71 mmol/L | 0 |
| Creatinine >1.5 x ULN | 0 |
| Uric acid ≥505.75 μmol/L | 0 |
| Lactate dehydrogenase ≥3× ULN | 0 |
| Glucose ≤2.48 mmol/L | 4 |
| Glucose ≥11 mmol/L | 1 |
| Albumin ≤26 g/L | 2 |
| Albumin ≥60 g/L | 0 |
| Protein ≤50 g/L | 1 |
| Protein ≥100 g/L | 0 |
| ALT ≥3× ULN | 14 |
| AST ≥3× ULN | 0 |
| GGT ≥3× ULN | 4 |
| ALP ≥3× ULN | 0 |
| Bilirubin ≥1.5× ULN | 0 |
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.
| score on a scale | Trofinetide |
|---|---|
| Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score Change From Baseline to Week 40 | -2.9 ± 1.17 |
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.
| score on a scale | Placebo/Trofinetide | Trofinetide/Trofinetide |
|---|---|---|
| Clinical Global Impression-Improvement (CGI-I) Score at Week 40 | 3.2 ± 0.14 | 3.1 ± 0.11 |
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.
| score on a scale | Trofinetide |
|---|---|
| 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 ± 0.26 |
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.
| score on a scale | Trofinetide |
|---|---|
| Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND) Change From Baseline to Week 40 | 0.2 ± 0.09 |
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
| score on a scale | Trofinetide |
|---|---|
| Rett Syndrome Clinician Rating of Hand Function (RTT-HF) Change From Baseline to Week 40 | -0.1 ± 0.09 |
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.
| score on a scale | Trofinetide |
|---|---|
| Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB) Change From Baseline to Week 40 | -0.2 ± 0.09 |
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.
| score on a scale | Trofinetide |
|---|---|
| Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC) Change From Baseline to Week 40 | -0.4 ± 0.13 |
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.
| score on a scale | Trofinetide |
|---|---|
| Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM) Change From Baseline to Week 40 | -0.2 ± 0.07 |
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.
| score on a scale | Trofinetide |
|---|---|
| Change From Baseline to Week 40 in Clinical Global Impression-Severity (CGI-S) | -0.1 ± 0.04 |
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.
| score on a scale | Trofinetide |
|---|---|
| Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (Items 1-24) Change From Baseline to Week 40 | -1.9 ± 1.05 |
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.
| score on a scale | Trofinetide |
|---|---|
| Impact of Childhood Neurologic Disability Scale (ICND) Total Score Change From Baseline to Week 40 | -5.8 ± 3.91 |
Collected over 44 weeks (including 40-week open-label treatment period and 30-day safety follow-up period). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Trofinetide | 0/154 (0%) | 19/154 (12.3%) | 114/154 (74%) |
| Event | Trofinetide |
|---|---|
| SeizureNervous system disorders | 5/154 |
| PneumoniaInfections and infestations | 4/154 |
| DehydrationMetabolism and nutrition disorders | 3/154 |
| PyrexiaGeneral disorders | 2/154 |
| Rhinovirus infectionInfections and infestations | 2/154 |
| Viral infectionInfections and infestations | 2/154 |
| Status epilepticusNervous system disorders | 2/154 |
| Acute respiratory failureRespiratory, thoracic and mediastinal disorders | 2/154 |
| AnaemiaBlood and lymphatic system disorders | 1/154 |
| Gastrointestinal haemorrhageGastrointestinal disorders | 1/154 |
| Event | Trofinetide |
|---|---|
| DiarrhoeaGastrointestinal disorders | 91/154 |
| VomitingGastrointestinal disorders | 39/154 |
| COVID-19Infections and infestations | 16/154 |
| Upper respiratory tract infectionInfections and infestations | 12/154 |
| PyrexiaGeneral disorders | 11/154 |
| Decreased appetiteMetabolism and nutrition disorders | 10/154 |
| SeizureNervous system disorders | 10/154 |
| Urinary tract infectionInfections and infestations | 9/154 |
| Weight decreasedInvestigations | 9/154 |
| Age, Continuous(years) | Trofinetide |
|---|---|
| Mean | 11.0 ± 4.55 |
| Sex: Female, Male(Participants) | Trofinetide |
|---|---|
| Female | 154 |
| Male | 0 |
| Race (NIH/OMB)(Participants) | Trofinetide |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 5 |
| Native Hawaiian or Other Pacific Islander | 1 |
| Black or African American | 1 |
| White | 143 |
| More than one race | 0 |
| Unknown or Not Reported | 4 |
| Height(cm) | Trofinetide |
|---|---|
| Mean | 128.60 ± 1.229 |
| Weight(kg) | Trofinetide |
|---|---|
| Mean | 29.28 ± 0.869 |
| Body Mass Index(kg/m2) | Trofinetide |
|---|---|
| Mean | 17.03 ± 0.285 |
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ACADIA Pharmaceuticals Inc.