Trial Outcomes & Findings for Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (LAVENDER™) (NCT NCT04181723)

NCT ID: NCT04181723

Last Updated: 2024-04-08

Results Overview

The RSBQ is a 45-item caregiver-completed rating scale that 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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 187 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2024-04-08

Participant Flow

Participant milestones

Measure	Drug - Trofinetide Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Overall Study STARTED	93	94
Overall Study COMPLETED	70	85
Overall Study NOT COMPLETED	23	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (LAVENDER™)

Baseline characteristics by cohort

Measure	Drug - Trofinetide n=93 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=94 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Total n=187 Participants Total of all reporting groups
Age, Categorical <=18 years	85 Participants n=5 Participants	89 Participants n=7 Participants	174 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	11 years STANDARD_DEVIATION 4.69 • n=5 Participants	10.9 years STANDARD_DEVIATION 4.57 • n=7 Participants	10.9 years STANDARD_DEVIATION 4.62 • n=5 Participants
Sex: Female, Male Female	93 Participants n=5 Participants	94 Participants n=7 Participants	187 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	86 Participants n=5 Participants	84 Participants n=7 Participants	170 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	82 Participants n=5 Participants	90 Participants n=7 Participants	172 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	93 participants n=5 Participants	94 participants n=7 Participants	187 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

The RSBQ is a 45-item caregiver-completed rating scale that 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	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score - Change From Baseline to Week 12	-4.9 score on a scale Standard Error 0.94	-1.7 score on a scale Standard Error 0.90

PRIMARY outcome

Timeframe: 12 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.

Outcome measures

Measure	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Clinical Global Impression-Improvement (CGI-I) Score at Week 12	3.5 score on a scale Standard Error 0.07	3.8 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: 12 Weeks Treatment Duration

Standardized screening scale for assessing communication and pre-linguistic skills in young children 12-24 months and can be used with older children with developmental delay. The CSBS-DP includes a suite of three separate measures: The Infant-Toddler Checklist, a follow-up Caregiver Questionnaire and a Behavior Sample. In this study only the Infant-Toddler (CSBS-DP-IT) Checklist was used. The CSBS-DP-IT Checklist is a 24-item rating scale and each item is scored using a three-level rating of frequency: "not yet", "sometimes" and "often". The CSBS-DP-IT Social Composite score the range was 0 to 26 and a higher score represented a worse outcome. Three composite scores can be calculated: 1) Social Composite; 2) Speech Composite; 3) Symbolic Composite.

Outcome measures

Measure	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Change From Baseline to Week 12 in Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social)	-0.1 score on a scale Standard Error 0.26	-1.1 score on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: 12 Weeks Treatment Duration

The Impact of Childhood Neurologic Disability (ICND) scale evaluates the effect of four conditions or health problems on 11 aspects of a child's or family's life as "A lot", "Some", "A little", "Not at all", or "Does not apply". The four conditions or health problems are 1) inattentiveness, impulsivity, or mood, 2) ability to think and remember, 3) neurologic or physical limitations, and 4) epilepsy. The ICND score the range of 0 to 132 and a higher score represents a worse outcome.

Outcome measures

Measure	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Change From Baseline to Week 12 in Impact of Childhood Neurologic Disability Scale (ICND) Total Score	-6.5 score on a scale Standard Error 3.44	-1.9 score on a scale Standard Error 3.14

SECONDARY outcome

Timeframe: 12 Weeks Treatment Duration

Clinical assessment of the subject's ability to use their hands for functional purposes (such as reaching for and grasping objects, self-feeding, or drawing). 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	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Hand Function (RTT-HF)	-0.1 score on a scale Standard Error 0.08	0.0 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: 12 Weeks Treatment Duration

Clinical assessment of the subject's ability to sit, stand, and ambulate (e.g., walking, running, and climbing stairs). The assessment was made on an 8-point Likert scale (0 to 7), with 0 denoting normal functioning and 7 as the most severe impairment.

Outcome measures

Measure	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB)	-0.2 score on a scale Standard Error 0.07	0.0 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: 12 Weeks Treatment Duration

Clinical assessment of the subject's ability to communicate their 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	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC)	-0.4 score on a scale Standard Error 0.11	0.0 score on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: 12 Weeks Treatment Duration

Clinical assessment of the subject's ability to communicate verbally (e.g. words and phrases). 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	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Change From Baseline to Week 12 in Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM)	0.0 score on a scale Standard Error 0.06	0.0 score on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: 12 Weeks Treatment Duration

A 7 point scale that rates 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. 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.

Outcome measures

Measure	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Change From Baseline to Week 12 in Clinical Global Impression-Severity (CGI-S)	0.0 score on a scale Standard Error 0.03	0.0 score on a scale Standard Error 0.03

SECONDARY outcome

Timeframe: 12 Weeks Treatment Duration

The Rett Syndrome Caregiver Burden Inventory (RTT-CBI) scale is intended to directly address caregiver burden and indirectly assess the significance of treatment effects on function in the context of activities of daily living. Ratings are on a 5-point Likert scale including: 0-never; 1-rarely; 2-sometimes; 3-frequently and 4-nearly always. As in the original Caregiver Burden Inventory, the RTT-CBI has 24 negatively worded items (items 1 through 24) yielding a total score up to 96. The RTT-CBI the range is 0 to 96 and a higher score represents a worse outcome.

Outcome measures

Measure	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Change From Baseline to Week 12 in Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (Items 1-24)	-1.1 score on a scale Standard Error 1.01	-0.4 score on a scale Standard Error 0.96

SECONDARY outcome

Timeframe: 12 Weeks Treatment Duration

The overall quality of life of the subject is also rated by responding to the following: "Please rate your child's overall 'Quality of Life' on the scale below. Choose the number which you feel is best and circle it." The choices range from 1 ("Poor") to 6 ("Excellent").

Outcome measures

Measure	Drug - Trofinetide n=91 Participants Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=93 Participants Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Change From Baseline to Week 12 in Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND)	0.2 score on a scale Standard Error 0.09	0.1 score on a scale Standard Error 0.09

Adverse Events

Drug - Trofinetide

Serious events: 3 serious events

Other events: 81 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Measure	Drug - Trofinetide n=93 participants at risk Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=94 participants at risk Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Gastrointestinal disorders Constipation	0.00% 0/93 • Approximately 4 months	1.1% 1/94 • Approximately 4 months
Gastrointestinal disorders Pneumatosis intestinalis	0.00% 0/93 • Approximately 4 months	1.1% 1/94 • Approximately 4 months
Infections and infestations Bacteraemia	1.1% 1/93 • Approximately 4 months	0.00% 0/94 • Approximately 4 months
Infections and infestations Bronchiolitis	1.1% 1/93 • Approximately 4 months	0.00% 0/94 • Approximately 4 months
Infections and infestations COVID-19 pneumonia	1.1% 1/93 • Approximately 4 months	0.00% 0/94 • Approximately 4 months
Infections and infestations Urinary tract infection	1.1% 1/93 • Approximately 4 months	0.00% 0/94 • Approximately 4 months
Nervous system disorders Seizure	1.1% 1/93 • Approximately 4 months	0.00% 0/94 • Approximately 4 months
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/93 • Approximately 4 months	1.1% 1/94 • Approximately 4 months

Other adverse events

Measure	Drug - Trofinetide n=93 participants at risk Trofinetide solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Trofinetide: Trofinetide solution administered based on the subject's weight at Baseline, twice daily for 12 weeks	Placebo n=94 participants at risk Trofinetide placebo solution of 30-60 mL based on the subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube) Placebo: Trofinetide placebo solution administered based on the subject's weight at Baseline, twice daily for 12 weeks
Gastrointestinal disorders Diarrhoea	80.6% 75/93 • Approximately 4 months	19.1% 18/94 • Approximately 4 months
Gastrointestinal disorders Vomiting	26.9% 25/93 • Approximately 4 months	9.6% 9/94 • Approximately 4 months
General disorders Pyrexia	8.6% 8/93 • Approximately 4 months	4.3% 4/94 • Approximately 4 months
Metabolism and nutrition disorders Decreased appetite	5.4% 5/93 • Approximately 4 months	2.1% 2/94 • Approximately 4 months
Nervous system disorders Seizure	7.5% 7/93 • Approximately 4 months	5.3% 5/94 • Approximately 4 months
Psychiatric disorders Irritability	6.5% 6/93 • Approximately 4 months	0.00% 0/94 • Approximately 4 months

Additional Information

Study Director

Acadia Pharmaceuticals Inc.

Phone: 844-422-2342

Email: medicalinformation@acadia-pharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place