Rett SyndromePhase 3NCT04776746

Open-Label Extension Study of Trofinetide for Rett Syndrome

A Phase 3 study testing trofinetide in people with Rett Syndrome, run by ACADIA Pharmaceuticals Inc. at 21 sites in United States.

Terminated

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

Official record

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Trial summary

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

Who is it for?: Ages 5 to 21 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: 77 participants
Where: 21 sitesUnited States
Study dates: 8 Nov 2020to 30 Jun 2023
Phase: Phase 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 5 to 21 years
Women only
No healthy volunteers
Child, Adult

Who may be able to join

Has completed the EOT visit of the antecedent trofinetide Study ACP-2566-004 (i.e., has completed 40 weeks)
May benefit from continued treatment with open-label trofinetide in the judgment of the Investigator
Can still 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
Childbearing Potential
Subjects of childbearing potential must abstain from sexual activity for the duration of the study and for at least 30 days thereafter. If a subject is sexually active or becomes sexually active during the study, she must use 2 clinically acceptable methods of contraception (e.g., oral, intrauterine device [IUD], diaphragm plus spermicide, injectable, transdermal or implantable contraception) for the duration of the study and for at least 30 days thereafter. Subject must not be pregnant or breastfeeding.

Who cannot join

Began treatment with growth hormone during the antecedent study
Began treatment with IGF-1 during the antecedent study
Began treatment with insulin during the antecedent study
Has developed a 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)
Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study due to AEs, medical condition, or noncompliance with investigational product or study procedures in the antecedent study
Has a clinically significant abnormality in vital signs at Baseline

Show all 9Show fewer

Has an average QTcF interval of >450 ms on the Baseline ECG performed before the first dose of trofinetide is given in the present study (i.e., the ECG performed at the EOT visit of the antecedent study)
Has developed a clinically significant ECG finding during the antecedent study
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 pre-specified entry criteria).

Trial locations and contacts

21 sites in 1 country.

City, postcode or hospital

21 sites in 1 country

United States21 sites

Emory Genetics Clinical Trial Center
Atlanta, Georgia, 30322
Children's Hospital Colorado Aurora
Aurora, Colorado, 80045
Kennedy Krieger Institute, John Hopkins School of Medicine
Baltimore, Maryland, 21205
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Boston Children's Hospital Harvard Medical School
Boston, Massachusetts, 02115
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Rush University Medical Center
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Cleveland Clinic
Cleveland, Ohio, 44195
Greenwood Genetic Center
Greenwood, South Carolina, 29646
Texas Children's Hospital
Houston, Texas, 77030
University of California, San Diego
La Jolla, California, 92037
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Translational Genomics Research Institute (TGen)
Phoenix, Arizona, 85012
UC Davis MIND Institute
Sacramento, California, 95817
Gillette Children's Specialty Healthcare
Saint Paul, Minnesota, 55101
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
University of South Florida
Tampa, Florida, 33612
Montefiore Medical Center
The Bronx, New York, 10467

Other trials in United States

About this study

Official title: An Open-Label Extension Study of Continuing Treatment With Trofinetide for Rett Syndrome

To investigate the safety and tolerability of continued long-term treatment with oral trofinetide in girls and women 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
Study drug is administered twice a day for up to approximately 32 months. Doses may be taken orally or administered by gastrostomy (G) tube. The subject's assigned dose for this study will be the final dose from the antecedent study (ACP-2566-004).

Study groups in NCT04776746
Study group	Role	What they receive
Drug - trofinetide	Experimental	trofinetide oral solution Receives: Drug: trofinetide

What is being measured

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

Percentage of Patients With Treatment-emergent Adverse Events (TEAEs), With Serious Adverse Events (SAEs), and With Withdrawals Due to AEs
Withdrawals due to AEs included both study drug discontinuation as well as study termination
Measured: Mean study drug exposure was 426 days, corresponding to 1.2 years
Number (%) of Patients With Potentially Clinically Important Changes in ECG Post-baseline
Potentially clinically significant ECG changes were defined as QTcF >500 ms or QTcF change from baseline (CFB) of >60 ms
Measured: Mean study drug exposure was 426 days, corresponding to 1.2 years
Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline
Potentially 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.
Measured: Mean study drug exposure was 426 days, corresponding to 1.2 years
Number (%) of Patients With Potentially Clinically Important Changes in Body Weight Post-baseline
Potentially clinically important changes from baseline in body weight were defined as:
Weight increase ≥7% from baseline Weight decrease ≥7% from baseline
Measured: Mean study drug exposure was 426 days, corresponding to 1.2 years
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
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
Measured: Mean study drug exposure was 426 days, corresponding to 1.2 years

Timeline

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

8 Nov 202030 Jun 2023

First posted2 Mar 2021
Study start8 Nov 2020
Primary completion30 Jun 2023
Study completion30 Jun 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 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 77 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04776746
Sponsor's protocol ID: ACP-2566-005
Status last verified: Sep 2024
First submitted: 29 Nov 2020
Last updated: 27 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, Neul JL, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, Barrett AM, An D, Bishop KM, Youakim JM. Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study. Med. 2024 Oct 11;5(10):1275-1281.e2. doi: 10.1016/j.medj.2024.06.007. Epub 2024 Jul 17.
PubMed 39025065
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

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All Rett Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Extension Study of Continuing Treatment With Trofinetide for Rett Syndrome
ClinicalTrials.gov ID: NCT04776746
Acronym / sponsor ID: ACP-2566-005
Conditions: Rett Syndrome
Phase: Phase 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: 77 participants (actual)
Lead sponsor: ACADIA Pharmaceuticals Inc.Industry (pharma, biotech, devices)
Study start: 8 Nov 2020 (actual)
Primary completion: 30 Jun 2023 (actual)
Study completion: 30 Jun 2023 (actual)
First posted: 2 Mar 2021 (actual)
Results: Posted 27 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 continued long-term treatment with oral trofinetide in girls and women 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: trofinetidetrofinetide oral solution

Who may qualify

Ages: 5 to 21 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (6 listed)

Has completed the EOT visit of the antecedent trofinetide Study ACP-2566-004 (i.e., has completed 40 weeks)
May benefit from continued treatment with open-label trofinetide in the judgment of the Investigator
Can still 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
Childbearing Potential

Key exclusion criteria (9 listed)

Began treatment with growth hormone during the antecedent study
Began treatment with IGF-1 during the antecedent study
Began treatment with insulin during the antecedent study
Has developed a 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)
Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study due to AEs, medical condition, or noncompliance with investigational product or study procedures in the antecedent study

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
trofinetideStudy drug is administered twice a day for up to approximately 32 months. Doses may be taken orally or administered by gastrostomy (G) tube. The subject's assigned dose for this study will be the final dose from the antecedent study (ACP-2566-004).	Drug	Drug - trofinetide

Primary outcome

Percentage of Patients With Treatment-emergent Adverse Events (TEAEs), With Serious Adverse Events (SAEs), and With Withdrawals Due to AEs
Time frame: Mean study drug exposure was 426 days, corresponding to 1.2 years
Withdrawals due to AEs included both study drug discontinuation as well as study termination
Number (%) of Patients With Potentially Clinically Important Changes in ECG Post-baseline
Time frame: Mean study drug exposure was 426 days, corresponding to 1.2 years
Potentially clinically significant ECG changes were defined as QTcF >500 ms or QTcF change from baseline (CFB) of >60 ms
Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline
Time frame: Mean study drug exposure was 426 days, corresponding to 1.2 years
Potentially 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.
Number (%) of Patients With Potentially Clinically Important Changes in Body Weight Post-baseline
Time frame: Mean study drug exposure was 426 days, corresponding to 1.2 years
Potentially clinically important changes from baseline in body weight were defined as: Weight increase ≥7% from baseline Weight decrease ≥7% from baseline
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline
Time frame: Mean study drug exposure was 426 days, corresponding to 1.2 years
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

Results and safety

Results posted to the registry on 27 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	77	0

Primary outcome: Percentage of Patients With Treatment-emergent Adverse Events (TEAEs), With Serious Adverse Events (SAEs), and With Withdrawals Due to AEs

Time frame: Mean study drug exposure was 426 days, corresponding to 1.2 years. Count of participants. Unit: Participants

Measure	Trofinetide n = 77
Patients with TEAEs	68
Patients with SAEs	23
Patients with AEs leading to discontinuation	9

Population analysed: All patients enrolled and treated

Primary outcome: Number (%) of Patients With Potentially Clinically Important Changes in ECG Post-baseline

Time frame: Mean study drug exposure was 426 days, corresponding to 1.2 years. Count of participants. Unit: Participants

Measure	Trofinetide n = 77
QTcF >500 ms	0
QTcF CFB >60 ms	1

Population analysed: All patients enrolled and treated

Primary outcome: Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline

Time frame: Mean study drug exposure was 426 days, corresponding to 1.2 years. Count of participants. Unit: Participants

Measure	Trofinetide n = 77
SBP≥180 mmHg and increased ≥20 mmHg from BL	0
SBP≤90 mmHg and decreased ≥20 mmHg from BL	5
DBP≥105 mmHg and increased ≥15 mmHg from BL	1
DBP≤50 mmHg and decreased ≥15 mmHg from BL	4
PR≥120 bpm and increased ≥15 bpm from BL	4
PR≤50 bpm and decreased ≥15 bpm from BL	0

Primary outcome: Number (%) of Patients With Potentially Clinically Important Changes in Body Weight Post-baseline

Time frame: Mean study drug exposure was 426 days, corresponding to 1.2 years. Count of participants. Unit: Participants

Measure	Trofinetide n = 77
Weight increase ≥7% from BL	45
Weight decrease ≥7% from BL	9

Adverse events

Time frame: Mean study drug exposure was 426 days, corresponding to 1.2 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Trofinetide	23 of 77 (29.9%)	57 of 77 (74%)	4 of 77

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. Date of study termination was 30 June 2023.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 39025065Percy AK, Neul JL, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, Barrett AM, An D, Bishop KM, Youakim JM. Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study. Med. 2024 Oct 11;5(10):1275-1281.e2. doi: 10.1016/j.medj.2024.06.007. Epub 2024 Jul 17.
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

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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.

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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing trofinetide in people with Rett Syndrome, run by ACADIA Pharmaceuticals Inc. at 21 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 6 inclusion and 9 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 27 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 21 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 phase mean?

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 27 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?

Percentage of Patients With Treatment-emergent Adverse Events (TEAEs), With Serious Adverse Events (SAEs), and With Withdrawals Due to AEs (time frame: Mean study drug exposure was 426 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 NCT04776746, 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 27 Sep 2024.