Rett SyndromePhase 2/3DAFFODIL™NCT04988867

An Open-Label Study of Trofinetide for the Treatment of Girls Two to Five Years of Age Who Have Rett Syndrome

A Phase 2/3 study testing Trofinetide in people with Rett Syndrome, run by ACADIA Pharmaceuticals Inc. at 7 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

To investigate the safety and tolerability of long-term treatment with oral trofinetide in girls with Rett syndrome Read more about this study

Who is it for?: Ages 2 to 5 years, women only
Conditions the study is for: Rett Syndrome
What is being tested?: Trofinetide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 7 sitesUnited States
Study dates: 22 Sep 2021to 31 May 2023
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 5 years
Women only
No healthy volunteers
Child

Who may be able to join

Female subject
2 to 4 years of age and body weight ≥9 kg and <20 kg at Screening OR
5 years of age and body weight ≥9 kg and <12 kg at Screening
Can swallow the study medication provided as a liquid solution or can take it by gastrostomy tube
The subject's caregiver is English-speaking and has sufficient language skills to complete the caregiver assessments
Has classic/typical Rett syndrome (RTT) or possible RTT according to the Rett Syndrome Diagnostic Criteria

Show all 9Show fewer

Has a documented disease-causing mutation in the MECP2 gene
Has a stable pattern of seizures, or has had no seizures, within 8 weeks prior to Screening
Subject and caregiver(s) must reside at a location to which study drug can be delivered and have been at their present residence for at least 4 weeks prior to Screening

Who cannot join

Has been treated with insulin within 12 weeks of Baseline
Has current clinically significant cardiovascular, endocrine (such as hypo- or hyperthyroidism, Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus), renal, hepatic, respiratory or gastrointestinal disease (such as celiac disease or inflammatory bowel disease) or has major surgery planned during the study
Has a history of, or current, cerebrovascular disease or brain trauma
Has significant, uncorrected visual or uncorrected hearing impairment
Has a history of, or current, malignancy
Has any of the following:

Show all 11Show fewer

QTcF interval of >450 ms at Screening or Baseline
History of a risk factor for torsades de pointes (e.g., heart failure or family history of long QT syndrome)
History of clinically significant QT prolongation that is deemed to put the subject at increased risk of clinically significant QT prolongation
Other clinically significant finding on ECG at Screening or Baseline
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).

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Children's Hospital Colorado
Aurora, Colorado, 80045
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Boston Children's Hospital/Harvard Medical School
Boston, Massachusetts, 02115
Rush University Medical Center
Chicago, Illinois, 60612
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Gillette Children's Hospital
Saint Paul, Minnesota, 55101
Washington University
St Louis, Missouri, 63110

Other trials in United States

About this study

To investigate the safety and tolerability of long-term treatment with oral trofinetide in girls with Rett syndrome

Conditions: Rett Syndrome
Being tested: Trofinetide
Medical subject headings: Rett Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TrofinetideDrug
Trofinetide solution of 10-30 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)

Study groups in NCT04988867
Study group	Role	What they receive
Drug - trofinetide	Experimental	Oral dose of trofinetide Receives: Drug: Trofinetide

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety and Tolerability of Treatment With Oral Trofinetide
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)
Measured: Mean study drug exposure 434 days, corresponding to 1.2 years
AUC0-12,ss (Area Under the Concentration-time Curve From Time 0 to 12 h at Steady State)
Area under the concentration-time curve from time 0 to 12 h at steady state as obtained from population pharmacokinetic (PK) modelling
Measured: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Cmax,ss (Maximum Observed Drug Concentration at Steady State)
Maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling
Measured: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Cmin,ss (Minimum Observed Drug Concentration at Steady State of Oral Trofinetide)
Minimum observed drug concentration at steady state of oral trofinetide as obtained from population pharmacokinetic (PK) modeling
Measured: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Tmax (Time of the Maximum Observed Drug Concentration at Steady State)
Time of the maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling
Measured: PK samples were taken predose and at Weeks 2, 4, 8, and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Sep 202131 May 2023

First posted4 Aug 2021
Study start22 Sep 2021
Primary completion31 May 2023
Study completion31 May 2023

Why it stopped: As a result of marketing approval of trofinetide on 10 March 2023, the study was terminated by the Sponsor with the intent of switching patients to commercially available product.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Rett SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04988867
Sponsor's protocol ID: ACP-2566-009
Acronym: DAFFODIL™
Status last verified: Sep 2024
First submitted: 23 Jul 2021
Last updated: 24 Sep 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Percy AK, Ryther R, Marsh ED, Neul JL, Benke TA, Berry-Kravis EM, Feyma T, Lieberman DN, Ananth AL, Fu C, Buhrfiend C, Barrett A, Doshi D, Darwish M, An D, Bishop KM, Youakim JM. Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome. Med. 2025 Jun 13;6(6):100608. doi: 10.1016/j.medj.2025.100608. Epub 2025 Mar 4.
PubMed 40043705
Parent H, Ferranti A, Niswender C. Trofinetide: a pioneering treatment for Rett syndrome. Trends Pharmacol Sci. 2023 Oct;44(10):740-741. doi: 10.1016/j.tips.2023.06.008. Epub 2023 Jul 16.
PubMed 37460385

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
A Phase 3 Study of Fenfluramine Hydrochloride in Rett Syndrome
Rett Syndrome
Active, not recruiting
Measuring Impact of Computer Gaming on Arm Use in Rett Syndrome
Rett Syndrome
Active, not recruiting
Technology-supported Motor Rehabilitation for People With Rett Syndrome
Rett Syndrome
RecruitingObservational study
Neurophysiologic Biomarkers in Rett Syndrome
Rett Syndrome, RTT
RecruitingPhase 1/2
ATTUNE: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome (MDS)
Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome

All Rett Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Study of Trofinetide for the Treatment of Girls Two to Five Years of Age Who Have Rett Syndrome
ClinicalTrials.gov ID: NCT04988867
Acronym / sponsor ID: DAFFODIL™ / ACP-2566-009
Conditions: Rett Syndrome
Phase: Phase 2/3
Study type: Interventional
Recruitment status: TerminatedReason stopped: As a result of marketing approval of trofinetide on 10 March 2023, the study was terminated by the Sponsor with the intent of switching patients to commercially available product.
Enrolment: 15 participants (actual)
Lead sponsor: ACADIA Pharmaceuticals Inc.Industry (pharma, biotech, devices)
Study start: 22 Sep 2021 (actual)
Primary completion: 31 May 2023 (actual)
Study completion: 31 May 2023 (actual)
First posted: 4 Aug 2021 (actual)
Results: Posted 24 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To investigate the safety and tolerability of long-term treatment with oral trofinetide in girls with Rett syndrome

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Drug - trofinetide	Experimental	Drug: TrofinetideOral dose of trofinetide

Who may qualify

Ages: 2 to 5 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (9 listed)

Female subject
Can swallow the study medication provided as a liquid solution or can take it by gastrostomy tube
The subject's caregiver is English-speaking and has sufficient language skills to complete the caregiver assessments
Has classic/typical Rett syndrome (RTT) or possible RTT according to the Rett Syndrome Diagnostic Criteria
Has a documented disease-causing mutation in the MECP2 gene

Key exclusion criteria (11 listed)

Has been treated with insulin within 12 weeks of Baseline
Has current clinically significant cardiovascular, endocrine (such as hypo- or hyperthyroidism, Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus), renal, hepatic, respiratory or gastrointestinal disease (such as celiac disease or inflammatory bowel disease) or has major surgery planned during the study
Has a history of, or current, cerebrovascular disease or brain trauma
Has significant, uncorrected visual or uncorrected hearing impairment
Has a history of, or current, malignancy

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TrofinetideTrofinetide solution of 10-30 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)	Drug	Drug - trofinetide

Primary outcome

Safety and Tolerability of Treatment With Oral Trofinetide
Time frame: Mean study drug exposure 434 days, corresponding to 1.2 years
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)
AUC0-12,ss (Area Under the Concentration-time Curve From Time 0 to 12 h at Steady State)
Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Area under the concentration-time curve from time 0 to 12 h at steady state as obtained from population pharmacokinetic (PK) modelling
Cmax,ss (Maximum Observed Drug Concentration at Steady State)
Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling
Cmin,ss (Minimum Observed Drug Concentration at Steady State of Oral Trofinetide)
Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Minimum observed drug concentration at steady state of oral trofinetide as obtained from population pharmacokinetic (PK) modeling
Tmax (Time of the Maximum Observed Drug Concentration at Steady State)
Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Time of the maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling

Results and safety

Results posted to the registry on 24 Sep 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Trofinetide	15	0

Primary outcome: Safety and Tolerability of Treatment With Oral Trofinetide

Time frame: Mean study drug exposure 434 days, corresponding to 1.2 years. Count of participants. Unit: Participants

Measure	Trofinetide n = 15
Patients with TEAEs	14
Patients with SAEs	4
Patients with AEs leading to discontinuation	2
Alanine transaminase ≥3 ULN	1
Aspartate transaminase ≥3 ULN	1
Potassium ≤3.0 mmol/L	1
Leukocytes ≥15 × 10Ê9/L	2
Neutrophils ≤1.5 × 10E9/L	2

Population analysed: All patients enrolled and treated

Primary outcome: AUC0-12,ss (Area Under the Concentration-time Curve From Time 0 to 12 h at Steady State)

Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12. Mean (Standard Deviation). Unit: μg x h/mL

Measure	Trofinetide n = 13
Value	1015.7 (135.9)

Population analysed: Patients enrolled, treated, and with at least one quantifiable PK concentration

Primary outcome: Cmax,ss (Maximum Observed Drug Concentration at Steady State)

Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12. Mean (Standard Deviation). Unit: μg/mL

Measure	Trofinetide n = 13
Value	181.5 (22.8)

Population analysed: Patients enrolled, treated, and with at least one quantifiable PK concentration

Primary outcome: Cmin,ss (Minimum Observed Drug Concentration at Steady State of Oral Trofinetide)

Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12. Mean (Standard Deviation). Unit: μg/mL

Measure	Trofinetide n = 13
Value	19.6 (6.3)

Population analysed: Patients enrolled, treated, and with at least one quantifiable PK concentration

Adverse events

Time frame: Mean study drug exposure 434 days, corresponding to 1.2 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Trofinetide	4 of 15 (26.7%)	14 of 15 (93.3%)	0 of 15

Limitations and caveats (from the sponsor): As a result of marketing approval of trofinetide on 10 March 2023, the study was terminated by the Sponsor with the intent of switching patients to commercially available product. The study was terminated on 31 May 2023.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40043705Percy AK, Ryther R, Marsh ED, Neul JL, Benke TA, Berry-Kravis EM, Feyma T, Lieberman DN, Ananth AL, Fu C, Buhrfiend C, Barrett A, Doshi D, Darwish M, An D, Bishop KM, Youakim JM. Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome. Med. 2025 Jun 13;6(6):100608. doi: 10.1016/j.medj.2025.100608. Epub 2025 Mar 4.
Derived from this study: PubMed 37460385Parent H, Ferranti A, Niswender C. Trofinetide: a pioneering treatment for Rett syndrome. Trends Pharmacol Sci. 2023 Oct;44(10):740-741. doi: 10.1016/j.tips.2023.06.008. Epub 2023 Jul 16.
Individual participant dataSharing planned: No

Related trials for Rett Syndrome

RecruitingPhase 3
A Phase 3 Study of Fenfluramine Hydrochloride in Rett Syndrome
Rett Syndrome
Active, not recruiting
Measuring Impact of Computer Gaming on Arm Use in Rett Syndrome
Rett Syndrome
Active, not recruiting
Technology-supported Motor Rehabilitation for People With Rett Syndrome
Rett Syndrome
RecruitingObservational study
Neurophysiologic Biomarkers in Rett Syndrome
Rett Syndrome, RTT
RecruitingPhase 1/2
ATTUNE: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome (MDS)
Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Trofinetide in people with Rett Syndrome, run by ACADIA Pharmaceuticals Inc. at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability of Treatment With Oral Trofinetide (time frame: Mean study drug exposure 434 days, corresponding to 1.2 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04988867, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2024.