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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.
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To investigate the safety and tolerability of continued long-term treatment with oral trofinetide in girls and women with Rett syndrome
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Drug - trofinetide | Experimental | trofinetide oral solution |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| trofinetide | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | 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. | 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 | 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 |
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Inclusion Criteria:
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.
Exclusion Criteria:
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).
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| Translational Genomics Research Institute (TGen) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39025065 | Background | 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. | |
| 37460385 |
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This was a multicenter, open-label, long-term study of trofinetide to monitor the safety and efficacy of continuing trofinetide therapy for patients who previously completed a Phase 3 trofinetide study. Patients who completed the preceding open-label study ACP-2566-004 were eligible to enroll in this study. Study ACP-2566-004 was an extension study for randomized, double-blind, placebo-controlled study ACP-2566-003.
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| ID | Title | Description |
|---|---|---|
| FG000 | Trofinetide | Trofinetide oral solution was administered twice daily for a planned duration of up to approximately 32 months, orally or administered by gastrostomy (G) tube. Treatment duration could be less than 32 months if trofinetide became commercially available during the study, or if development of trofinetide for Rett syndrome was discontinued. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 19, 2022 | Jul 15, 2024 |
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| Mean study drug exposure was 426 days, corresponding to 1.2 years |
| Phoenix |
| Arizona |
| 85012 |
| United States |
| University of California, San Diego | La Jolla | California | 92037 | United States |
| UC Davis MIND Institute | Sacramento | California | 95817 | United States |
| Children's Hospital Colorado Aurora | Aurora | Colorado | 80045 | United States |
| University of South Florida | Tampa | Florida | 33612 | United States |
| Emory Genetics Clinical Trial Center | Atlanta | Georgia | 30322 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Kennedy Krieger Institute, John Hopkins School of Medicine | Baltimore | Maryland | 21205 | United States |
| Boston Children's Hospital Harvard Medical School | Boston | Massachusetts | 02115 | United States |
| Gillette Children's Specialty Healthcare | Saint Paul | Minnesota | 55101 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Montefiore Medical Center | The Bronx | New York | 10467 | United States |
| The University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Greenwood Genetic Center | Greenwood | South Carolina | 29646 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Texas Children's Hospital | Houston | Texas | 77030 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| 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. |
| COMPLETED |
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| NOT COMPLETED |
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All patients enrolled and treated with trofinetide
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| ID | Title | Description |
|---|---|---|
| BG000 | Trofinetide | Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004). |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | All patients enrolled and treated | Posted | Count of Participants | Participants | Mean study drug exposure was 426 days, corresponding to 1.2 years |
|
|
| ||||||||||||||||||||||||||||||||||||
| Primary | 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 | All patients enrolled and treated | Posted | Count of Participants | Participants | Mean study drug exposure was 426 days, corresponding to 1.2 years |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | 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. | Posted | Count of Participants | Participants | Mean study drug exposure was 426 days, corresponding to 1.2 years |
|
| ||||||||||||||||||||||||||||||||||||||
| Primary | 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 | Posted | Count of Participants | Participants | Mean study drug exposure was 426 days, corresponding to 1.2 years |
|
| ||||||||||||||||||||||||||||||||||||||
| Primary | 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 | All patients enrolled and treated and with at least one postbaseline value for the respective parameter (n=75; apart from deviating patient numbers of n=74 for uric acid, LDH, AST and bilirubin) | Posted | Count of Participants | Participants | Mean study drug exposure was 426 days, corresponding to 1.2 years |
|
|
Mean study drug exposure was 426 days, corresponding to 1.2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Trofinetide | Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004). | 4 | 77 | 23 | 77 | 57 | 77 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac arrest | Cardiac disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Gastric perforation | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Gastric ulcer | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Pneumoperitoneum | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Sudden unexplained death in epilepsy | General disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Enterovirus infection | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Parainfluenzae virus infection | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Pneumonia viral | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Urinary tract infection fungal | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 24.0 | Non-systematic Assessment |
| |
| Renal procedural complication | Injury, poisoning and procedural complications | MedDRA 24.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Dystonia | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Dystonic tremor | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Status epilepticus | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Pelvic fluid collection | Reproductive system and breast disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 24.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Non-systematic Assessment |
|
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.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sr. Dir. Medical Information and Medical Communications | ACADIA Pharmaceuticals Inc. | +1-858-261 | 2897 | medicalinformation@acadia-pharm.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 26, 2023 | Jul 15, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015518 | Rett Syndrome |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020271 | Heredodegenerative Disorders, Nervous System |
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| ID | Term |
|---|---|
| C000656362 | trofinetide |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Title | Measurements |
|---|---|
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| Participants |
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