Trial Outcomes & Findings for An Open-Label Study of Trofinetide for the Treatment of Girls Two to Five Years of Age Who Have Rett Syndrome (NCT NCT04988867)
NCT ID: NCT04988867
Last Updated: 2024-09-24
Results Overview
Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), withdrawals due to AEs, potentially clinically important (PCI) changes in other safety assessments (laboratory values, vital signs, or ECGs, following protocol-defined PCI criteria)
Recruitment status
TERMINATED
Study phase
PHASE2/PHASE3
Target enrollment
15 participants
Primary outcome timeframe
Mean study drug exposure 434 days, corresponding to 1.2 years
Results posted on
2024-09-24
Participant Flow
Participant milestones
| Measure |
Trofinetide
Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube.
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
15
|
Reasons for withdrawal
| Measure |
Trofinetide
Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube.
|
|---|---|
|
Overall Study
Study terminated by Sponsor
|
12
|
|
Overall Study
Adverse Event
|
2
|
|
Overall Study
Study drug noncompliance
|
1
|
Baseline Characteristics
An Open-Label Study of Trofinetide for the Treatment of Girls Two to Five Years of Age Who Have Rett Syndrome
Baseline characteristics by cohort
| Measure |
Trofinetide
n=15 Participants
Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube.
|
|---|---|
|
Age, Continuous
|
3.1 years
STANDARD_DEVIATION 0.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 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
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Mean study drug exposure 434 days, corresponding to 1.2 yearsPopulation: All patients enrolled and treated
Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), withdrawals due to AEs, potentially clinically important (PCI) changes in other safety assessments (laboratory values, vital signs, or ECGs, following protocol-defined PCI criteria)
Outcome measures
| Measure |
Trofinetide
n=15 Participants
Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube.
|
|---|---|
|
Safety and Tolerability of Treatment With Oral Trofinetide
Patients with SAEs
|
4 Participants
|
|
Safety and Tolerability of Treatment With Oral Trofinetide
Patients with AEs leading to discontinuation
|
2 Participants
|
|
Safety and Tolerability of Treatment With Oral Trofinetide
Patients with TEAEs
|
14 Participants
|
|
Safety and Tolerability of Treatment With Oral Trofinetide
Alanine transaminase ≥3 ULN
|
1 Participants
|
|
Safety and Tolerability of Treatment With Oral Trofinetide
Aspartate transaminase ≥3 ULN
|
1 Participants
|
|
Safety and Tolerability of Treatment With Oral Trofinetide
Potassium ≤3.0 mmol/L
|
1 Participants
|
|
Safety and Tolerability of Treatment With Oral Trofinetide
Leukocytes ≥15 × 10Ê9/L
|
2 Participants
|
|
Safety and Tolerability of Treatment With Oral Trofinetide
Neutrophils ≤1.5 × 10E9/L
|
2 Participants
|
|
Safety and Tolerability of Treatment With Oral Trofinetide
Hematocrit <0.3
|
1 Participants
|
|
Safety and Tolerability of Treatment With Oral Trofinetide
Hemoglobin <100 g/L
|
1 Participants
|
PRIMARY outcome
Timeframe: PK samples were taken predose and at Weeks 2, 4, 8, and 12Population: Patients enrolled, treated, and with at least one quantifiable PK concentration
Area under the concentration-time curve from time 0 to 12 h at steady state as obtained from population pharmacokinetic (PK) modelling
Outcome measures
| Measure |
Trofinetide
n=13 Participants
Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube.
|
|---|---|
|
AUC0-12,ss (Area Under the Concentration-time Curve From Time 0 to 12 h at Steady State)
|
1015.7 μg x h/mL
Standard Deviation 135.9
|
PRIMARY outcome
Timeframe: PK samples were taken predose and at Weeks 2, 4, 8, and 12Population: Patients enrolled, treated, and with at least one quantifiable PK concentration
Maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling
Outcome measures
| Measure |
Trofinetide
n=13 Participants
Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube.
|
|---|---|
|
Cmax,ss (Maximum Observed Drug Concentration at Steady State)
|
181.5 μg/mL
Standard Deviation 22.8
|
PRIMARY outcome
Timeframe: PK samples were taken predose and at Weeks 2, 4, 8, and 12Population: Patients enrolled, treated, and with at least one quantifiable PK concentration
Minimum observed drug concentration at steady state of oral trofinetide as obtained from population pharmacokinetic (PK) modeling
Outcome measures
| Measure |
Trofinetide
n=13 Participants
Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube.
|
|---|---|
|
Cmin,ss (Minimum Observed Drug Concentration at Steady State of Oral Trofinetide)
|
19.6 μg/mL
Standard Deviation 6.3
|
PRIMARY outcome
Timeframe: PK samples were taken predose and at Weeks 2, 4, 8, and 12Population: Patients enrolled, treated, and with at least one quantifiable PK concentration
Time of the maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling
Outcome measures
| Measure |
Trofinetide
n=13 Participants
Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube.
|
|---|---|
|
Tmax (Time of the Maximum Observed Drug Concentration at Steady State)
|
1.8 h
Standard Deviation 0.2
|
Adverse Events
Trofinetide
Serious events: 4 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Trofinetide
n=15 participants at risk
Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube.
|
|---|---|
|
Gastrointestinal disorders
Dysphagia
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Gastroenteritis sapovirus
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Nervous system disorders
Seizure
|
13.3%
2/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Nervous system disorders
Altered state of consciousness
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
Other adverse events
| Measure |
Trofinetide
n=15 participants at risk
Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube.
|
|---|---|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Congenital, familial and genetic disorders
Rett syndrome
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Diarrhoea
|
80.0%
12/15 • Number of events 26 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Vomiting
|
53.3%
8/15 • Number of events 11 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
13.3%
2/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Constipation
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Dysphagia
|
6.7%
1/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Flatulence
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Gastrointestinal disorders
Toothache
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
General disorders
Pyrexia
|
33.3%
5/15 • Number of events 5 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
COVID-19
|
46.7%
7/15 • Number of events 9 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Gastroenteritis
|
33.3%
5/15 • Number of events 7 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Upper respiratory tract infection
|
26.7%
4/15 • Number of events 7 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Influenza
|
20.0%
3/15 • Number of events 3 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Conjunctivitis
|
13.3%
2/15 • Number of events 3 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Ear infection
|
13.3%
2/15 • Number of events 3 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Candida infection
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Croup infectious
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Oral candidiasis
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Otitis media
|
6.7%
1/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Otitis media acute
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Pharyngitis
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Pharyngitis streptococcal
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Pneumonia
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Sinusitis
|
6.7%
1/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Skin infection
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Viral infection
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Infections and infestations
Viral upper respiratory tract infection
|
6.7%
1/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Injury, poisoning and procedural complications
Fall
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Investigations
Weight decreased
|
13.3%
2/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Investigations
Alanine aminotransferase increased
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Investigations
Aspartate aminotransferase increased
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Metabolism and nutrition disorders
Feeding disorder
|
13.3%
2/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Musculoskeletal and connective tissue disorders
Scoliosis
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Nervous system disorders
Seizure
|
33.3%
5/15 • Number of events 9 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Nervous system disorders
Epilepsy
|
13.3%
2/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Nervous system disorders
Somnolence
|
13.3%
2/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Nervous system disorders
Altered state of consciousness
|
6.7%
1/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Psychiatric disorders
Irritability
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
3/15 • Number of events 4 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
20.0%
3/15 • Number of events 3 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis diaper
|
13.3%
2/15 • Number of events 2 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Skin and subcutaneous tissue disorders
Erythema
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 days, corresponding to 1.2 years
|
|
Skin and subcutaneous tissue disorders
Excessive granulation tissue
|
6.7%
1/15 • Number of events 1 • Mean study drug exposure 434 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