Trial Outcomes & Findings for Open-Label Extension Study of Trofinetide for Rett Syndrome (NCT NCT04776746)
NCT ID: NCT04776746
Last Updated: 2024-09-27
Results Overview
Withdrawals due to AEs included both study drug discontinuation as well as study termination
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
77 participants
Primary outcome timeframe
Mean study drug exposure was 426 days, corresponding to 1.2 years
Results posted on
2024-09-27
Participant Flow
This was a multicenter, open-label, long-term study of trofinetide to monitor the safety and efficacy of continuing trofinetide therapy for patients who previously completed a Phase 3 trofinetide study. Patients who completed the preceding open-label study ACP-2566-004 were eligible to enroll in this study. Study ACP-2566-004 was an extension study for randomized, double-blind, placebo-controlled study ACP-2566-003.
Participant milestones
| Measure |
Trofinetide
Trofinetide oral solution was administered twice daily for a planned duration of up to approximately 32 months, orally or administered by gastrostomy (G) tube. Treatment duration could be less than 32 months if trofinetide became commercially available during the study, or if development of trofinetide for Rett syndrome was discontinued.
|
|---|---|
|
Overall Study
STARTED
|
77
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
77
|
Reasons for withdrawal
| Measure |
Trofinetide
Trofinetide oral solution was administered twice daily for a planned duration of up to approximately 32 months, orally or administered by gastrostomy (G) tube. Treatment duration could be less than 32 months if trofinetide became commercially available during the study, or if development of trofinetide for Rett syndrome was discontinued.
|
|---|---|
|
Overall Study
Study terminated by sponsor
|
61
|
|
Overall Study
Adverse Event
|
5
|
|
Overall Study
Death
|
4
|
|
Overall Study
Lack of Efficacy
|
3
|
|
Overall Study
Noncompliance with study drug
|
2
|
|
Overall Study
Not related to COVID-19
|
2
|
Baseline Characteristics
Open-Label Extension Study of Trofinetide for Rett Syndrome
Baseline characteristics by cohort
| Measure |
Trofinetide
n=77 Participants
Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004).
|
|---|---|
|
Age, Continuous
|
12.0 years
STANDARD_DEVIATION 4.38 • n=5 Participants
|
|
Sex: Female, Male
Female
|
77 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
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
71 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
77 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Mean study drug exposure was 426 days, corresponding to 1.2 yearsPopulation: All patients enrolled and treated
Withdrawals due to AEs included both study drug discontinuation as well as study termination
Outcome measures
| Measure |
Trofinetide
n=77 Participants
Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004).
|
|---|---|
|
Percentage of Patients With Treatment-emergent Adverse Events (TEAEs), With Serious Adverse Events (SAEs), and With Withdrawals Due to AEs
Patients with TEAEs
|
68 Participants
|
|
Percentage of Patients With Treatment-emergent Adverse Events (TEAEs), With Serious Adverse Events (SAEs), and With Withdrawals Due to AEs
Patients with SAEs
|
23 Participants
|
|
Percentage of Patients With Treatment-emergent Adverse Events (TEAEs), With Serious Adverse Events (SAEs), and With Withdrawals Due to AEs
Patients with AEs leading to discontinuation
|
9 Participants
|
PRIMARY outcome
Timeframe: Mean study drug exposure was 426 days, corresponding to 1.2 yearsPopulation: All patients enrolled and treated
Potentially clinically significant ECG changes were defined as QTcF \>500 ms or QTcF change from baseline (CFB) of \>60 ms
Outcome measures
| Measure |
Trofinetide
n=77 Participants
Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004).
|
|---|---|
|
Number (%) of Patients With Potentially Clinically Important Changes in ECG Post-baseline
QTcF >500 ms
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in ECG Post-baseline
QTcF CFB >60 ms
|
1 Participants
|
PRIMARY outcome
Timeframe: Mean study drug exposure was 426 days, corresponding to 1.2 yearsPotentially clinically important changes from baseline in vital signs were defined 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 rate (PR) ≥120 bpm and increased ≥15 bpm from baseline; PR≤50 bpm and decreased ≥15 bpm from baseline. Baseline was the baseline value of previous study ACP-2566-003.
Outcome measures
| Measure |
Trofinetide
n=77 Participants
Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004).
|
|---|---|
|
Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline
SBP≥180 mmHg and increased ≥20 mmHg from BL
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline
SBP≤90 mmHg and decreased ≥20 mmHg from BL
|
5 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline
DBP≥105 mmHg and increased ≥15 mmHg from BL
|
1 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline
DBP≤50 mmHg and decreased ≥15 mmHg from BL
|
4 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline
PR≥120 bpm and increased ≥15 bpm from BL
|
4 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline
PR≤50 bpm and decreased ≥15 bpm from BL
|
0 Participants
|
PRIMARY outcome
Timeframe: Mean study drug exposure was 426 days, corresponding to 1.2 yearsPotentially clinically important changes from baseline in body weight were defined as: Weight increase ≥7% from baseline Weight decrease ≥7% from baseline
Outcome measures
| Measure |
Trofinetide
n=77 Participants
Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004).
|
|---|---|
|
Number (%) of Patients With Potentially Clinically Important Changes in Body Weight Post-baseline
Weight increase ≥7% from BL
|
45 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Body Weight Post-baseline
Weight decrease ≥7% from BL
|
9 Participants
|
PRIMARY outcome
Timeframe: Mean study drug exposure was 426 days, corresponding to 1.2 yearsPopulation: All patients enrolled and treated and with at least one postbaseline value for the respective parameter (n=75; apart from deviating patient numbers of n=74 for uric acid, LDH, AST and bilirubin)
Potentially clinically important changes in laboratory parameters were defined 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 \>2.75 mmol/L; blood urea nitrogen ≥10.71 mmol/L; creatinine \>1.5× upper limit of normal (ULN); uric acid ≥505.75 μmol/L; lactate dehydrogenase (LDH) ≥3×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 transaminase (ALT) ≥3×ULN; aspartate transaminase (AST) ≥3×ULN; gamma glutamyl transferase (GGT) ≥3×ULN; alkaline phosphatase (ALP) ≥3×ULN; bilirubin ≥1.5×ULN
Outcome measures
| Measure |
Trofinetide
n=75 Participants
Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004).
|
|---|---|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Sodium ≤125 mmol/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Sodium ≥155 mmol/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Potassium ≤3.0 mmol/L
|
1 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Potassium ≥5.5 mmol/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Chloride ≤85 mmol/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Chloride ≥120 mmol/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Calcium <2.0 mmol/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Calcium >2.75 mmol/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Blood urea nitrogen ≥10.71 mmol/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Creatinine >1.5× ULN
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Uric acid ≥505.75 μmol/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
LDH ≥3×ULN
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Glucose ≤2.48 mmol/L
|
1 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Glucose ≥11 mmol/L
|
1 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Albumin ≤26 g/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Albumin ≥60 g/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Protein ≤50 g/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Protein ≥100 g/L
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
ALT ≥3×ULN
|
2 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
AST ≥3×ULN
|
0 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
GGT ≥3×ULN
|
2 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
ALP ≥3×ULN
|
1 Participants
|
|
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Bilirubin ≥1.5×ULN
|
0 Participants
|
Adverse Events
Trofinetide
Serious events: 23 serious events
Other events: 57 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
Trofinetide
n=77 participants at risk
Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004).
|
|---|---|
|
Cardiac disorders
Cardiac arrest
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Vomiting
|
2.6%
2/77 • Number of events 2 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Abdominal pain
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Gastric perforation
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Gastric ulcer
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Pneumoperitoneum
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
General disorders
Pyrexia
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
General disorders
Sudden unexplained death in epilepsy
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Pneumonia
|
2.6%
2/77 • Number of events 2 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Urinary tract infection
|
2.6%
2/77 • Number of events 4 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
COVID-19
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Enterovirus infection
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Influenza
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Parainfluenzae virus infection
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Pharyngitis streptococcal
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Pneumonia viral
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Pyelonephritis
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Rhinovirus infection
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Staphylococcal infection
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Urinary tract infection fungal
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Injury, poisoning and procedural complications
Procedural pain
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Injury, poisoning and procedural complications
Renal procedural complication
|
1.3%
1/77 • Number of events 2 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Metabolism and nutrition disorders
Dehydration
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Nervous system disorders
Seizure
|
6.5%
5/77 • Number of events 6 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Nervous system disorders
Disturbance in attention
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Nervous system disorders
Dystonia
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Nervous system disorders
Dystonic tremor
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Nervous system disorders
Status epilepticus
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Reproductive system and breast disorders
Pelvic fluid collection
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
2.6%
2/77 • Number of events 3 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
1.3%
1/77 • Number of events 1 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
Other adverse events
| Measure |
Trofinetide
n=77 participants at risk
Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004).
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
16.9%
13/77 • Number of events 18 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Vomiting
|
13.0%
10/77 • Number of events 12 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Constipation
|
11.7%
9/77 • Number of events 9 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
General disorders
Pyrexia
|
15.6%
12/77 • Number of events 20 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
COVID-19
|
26.0%
20/77 • Number of events 22 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Urinary tract infection
|
15.6%
12/77 • Number of events 21 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Upper respiratory tract infection
|
11.7%
9/77 • Number of events 13 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Influenza
|
7.8%
6/77 • Number of events 6 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Pharyngitis streptococcal
|
6.5%
5/77 • Number of events 5 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Gastroenteritis viral
|
5.2%
4/77 • Number of events 4 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Pneumonia
|
5.2%
4/77 • Number of events 5 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Infections and infestations
Viral upper respiratory tract infection
|
5.2%
4/77 • Number of events 4 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Investigations
Electrocardiogram QT prolonged
|
5.2%
4/77 • Number of events 4 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Investigations
Weight decreased
|
5.2%
4/77 • Number of events 4 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Nervous system disorders
Seizure
|
10.4%
8/77 • Number of events 11 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Nervous system disorders
Lethargy
|
5.2%
4/77 • Number of events 7 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.8%
6/77 • Number of events 9 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.2%
4/77 • Number of events 5 • Mean study drug exposure was 426 days, corresponding to 1.2 years
|
Additional Information
Sr. Dir. Medical Information and Medical Communications
ACADIA Pharmaceuticals Inc.
Phone: +1-858-261
Email: [email protected]
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