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

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

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

Conditions
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Rett Syndrome

Intervention / Treatment
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* Drug: Trofinetide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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 Exclusion Criteria: 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: 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).

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug - trofinetide<br>Oral dose of trofinetide | Drug: Trofinetide<br>* Trofinetide solution of 10-30 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of treatment with oral trofinetide | Percentage of subjects with Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), withdrawals due to AEs, potentially clinically important changes in other safety assessments | Approximately 24 Months Treatment Duration | 
| Whole blood concentration of oral trofinetide |  | Pre-dose and Weeks 2, 4, 8, and 12 | 
| Area under the plasma concentration-time curve (AUC) |  | Pre-dose and Weeks 2, 4, 8, and 12 | 
| Maximum (peak) observed drug concentration (Cmax) |  | Pre-dose and Weeks 2, 4, 8, and 12 | 
| Apparent terminal elimination half-life (t½) |  | Pre-dose and Weeks 2, 4, 8, and 12 |