Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study.

Neul JL, Percy AK, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, Lin T, Stankovic S, Bishop KM, Youakim JM

Nature medicine8 Jun 2023Cited by 154 (Europe PMC)

PMID37291210PMCIDPMC10287558DOI10.1038/s41591-023-02398-1PepBankPUB-37291210

Summary

Rett syndrome is a rare, genetic neurodevelopmental disorder. Trofinetide is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of the insulin-like growth factor 1 protein, and has demonstrated clinical benefit in phase 2 studies in Rett syndrome. In this phase 3 study ( https://clinicaltrials.gov identifier NCT04181723 ), females with Rett syndrome received twice-daily oral trofinetide (n = 93) or placebo (n = 94) for 12 weeks. For the coprimary efficacy endpoints, least squares mean (LSM) change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire for trofinetide versus placebo was -4.9 versus -1.7 (P = 0.0175; Cohen's d effect size, 0.37), and LSM Clinical Global Impression-Improvement at week 12 was 3.5 versus 3.8 (P = 0.0030; effect size, 0.47). For the key secondary efficacy endpoint, LSM change from baseline to week 12 in the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist Social Composite score was -0.1 versus -1.1 (P = 0.0064; effect size, 0.43). Common treatment-emergent adverse events included diarrhea (80.6% for trofinetide versus 19.1% for placebo), which was mostly mild to moderate in severity. Significant improvement for trofinetide compared with placebo was observed for the coprimary efficacy endpoints, suggesting that trofinetide provides benefit in treating the core symptoms of Rett syndrome.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

01HumanRandomized controlled trialEfficacy outcome
In females with Rett syndrome, trofinetide reduced RSBQ scores more than placebo at week 12.
In plain wordsIn females with Rett syndrome, trofinetide reduced symptom scores more than placebo at week 12.
Peptide
Trofinetide
Outcome
DecreaseRSBQ change at week 12
Study
n = 187
Comparator
Placebo
Analysis
Primary
Outcome group
Rett Syndrome Symptoms · Nervous system and cognition
Studied dose
twice daily · oral · 12 weeksAs given in this study (human).
Measurements
LSM RSBQ change
−4.9 points
trofinetide
LSM RSBQ change
−1.7 points
placebo
P
0.0175
between groups
Cohen's d
0.37
between groups
Source sentences
Summary
For the coprimary efficacy endpoints, least squares mean (LSM) change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire for trofinetide versus placebo was -4.9 versus -1.7 (P = 0.0175; Cohen's d effect size, 0.37)
2 context sentences(design, population, supporting numbers)
Summary · context
In this phase 3 study ( https://clinicaltrials.gov identifier NCT04181723 ), females with Rett syndrome received twice-daily oral trofinetide (n = 93) or placebo (n = 94) for 12 weeks.
Title · context
Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study.
Show in the study text Report a problemFND-3729121001
02HumanRandomized controlled trialEfficacy outcome
In females with Rett syndrome, trofinetide produced lower CGI-I scores than placebo at week 12.
In plain wordsIn females with Rett syndrome, trofinetide produced better improvement ratings than placebo at week 12.
Peptide
Trofinetide
Outcome
DecreaseCGI-I at week 12
Study
n = 187
Comparator
Placebo
Analysis
Primary
Outcome group
Rett Syndrome Symptoms · Nervous system and cognition
Studied dose
twice daily · oral · 12 weeksAs given in this study (human).
Measurements
LSM CGI-I
3.5 points
trofinetide
LSM CGI-I
3.8 points
placebo
P
0.003
between groups
Effect size
0.47
between groups
Source sentences
Summary
and LSM Clinical Global Impression-Improvement at week 12 was 3.5 versus 3.8 (P = 0.0030; effect size, 0.47).
2 context sentences(design, population, supporting numbers)
Summary · context
In this phase 3 study ( https://clinicaltrials.gov identifier NCT04181723 ), females with Rett syndrome received twice-daily oral trofinetide (n = 93) or placebo (n = 94) for 12 weeks.
Title · context
Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study.
Show in the study text Report a problemFND-3729121002
03HumanRandomized controlled trialEfficacy outcome
In females with Rett syndrome, trofinetide produced a higher CSBS-DP-IT Social Composite change than placebo at week 12.
In plain wordsIn females with Rett syndrome, social communication scores declined less with trofinetide than placebo at week 12.
Peptide
Trofinetide
Outcome
IncreaseCSBS-DP-IT Social Composite change at week 12
Study
n = 187
Comparator
Placebo
Analysis
Secondary
Outcome group
Communication · Nervous system and cognition
Studied dose
twice daily · oral · 12 weeksAs given in this study (human).
Measurements
LSM score change
−0.1 points
trofinetide
LSM score change
−1.1 points
placebo
P
0.0064
between groups
Effect size
0.43
between groups
Source sentences
Summary
For the key secondary efficacy endpoint, LSM change from baseline to week 12 in the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist Social Composite score was -0.1 versus -1.1 (P = 0.0064; effect size, 0.43).
2 context sentences(design, population, supporting numbers)
Summary · context
In this phase 3 study ( https://clinicaltrials.gov identifier NCT04181723 ), females with Rett syndrome received twice-daily oral trofinetide (n = 93) or placebo (n = 94) for 12 weeks.
Title · context
Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study.
Show in the study text Report a problemFND-3729121003
04HumanRandomized controlled trialSafety outcome
In females with Rett syndrome, diarrhea occurred in 80.6% receiving trofinetide versus 19.1% receiving placebo, mostly with mild-to-moderate severity.
In plain wordsIn females with Rett syndrome, diarrhea occurred in 80.6% with trofinetide versus 19.1% with placebo, mostly with mild-to-moderate severity.
Peptide
Trofinetide
Outcome
IncreaseDiarrhea
Study
n = 187
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
twice daily · oral · 12 weeksAs given in this study (human).
Measurements
Diarrhea
80.6%
trofinetide
Diarrhea
19.1%
placebo
Source sentences
Summary
Common treatment-emergent adverse events included diarrhea (80.6% for trofinetide versus 19.1% for placebo), which was mostly mild to moderate in severity.
2 context sentences(design, population, supporting numbers)
Summary · context
In this phase 3 study ( https://clinicaltrials.gov identifier NCT04181723 ), females with Rett syndrome received twice-daily oral trofinetide (n = 93) or placebo (n = 94) for 12 weeks.
Title · context
Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study.
Show in the study text Report a problemFND-3729121004

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT04181723

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

ACADIA Pharmaceuticals Inc.n = 1876 Nov 2019 to 28 Oct 2021

Rett Syndrome

Trial page ClinicalTrials.govUpdated 8 Apr 2024

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:37 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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MeSH terms

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