An Open-Label Study of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)

Study Overview
=================
Brief Summary
-----------------
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Pitt Hopkins Syndrome.

Detailed Description
-----------------
The primary purpose of this study is to investigate the safety, tolerability and pharmacokinetics of treatment with NNZ-2591 oral solution in children and adolescents with Pitt Hopkins Syndrome. The secondary purpose is to investigate measures of efficacy. Subjects will receive treatment with NNZ-2591 oral solution (50 mg/mL) doses for a total of 13 weeks.

Official Title
-----------------
An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)

Conditions
-----------------
Pitt Hopkins Syndrome

Intervention / Treatment
-----------------
* Drug: NNZ-2591


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of PTHS with a documented disease-causing genetic etiology for the disorder. Males or females aged 3-17 years. Body weight of 12kg or higher at screening Subjects with a Clinical Global Impression- Severity (CGI-S) score of 4 or greater at the Screening visit. Not actively undergoing regression or loss of skills, defined as no persistent loss of previously acquired developmental skills for a period within 3 months of the Screening visit Each subject must be able to swallow the study medication provided as a liquid solution. Caregiver(s) must have sufficient English language skills. Exclusion Criteria: Body weight <12kg at screening Clinically significant abnormalities in safety laboratory tests and vital signs at Screening. Abnormal QTcF interval or prolongation at Screening. Any other clinically significant finding on ECG at the Screening visit. Positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and previous COVID 19 infection with last 12 months that required hospitalization. Unstable or changes Psychotropic treatment 2 weeks prior to screening Excluded concomitant treatments. Actively undergoing regression or loss of skills. Unstable seizure profile. Current clinically significant renal conditions and abnormalities Current clinically significant cardiovascular, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically significant organ impairment. Current clinically significant hypo- or hyperthyroidism, Type 1 or Type 2 diabetes mellitus requiring insulin (whether well controlled or uncontrolled), or uncontrolled Type 1 or Type 2 diabetes. Has planned surgery during the study. History of, or current, cerebrovascular disease or brain trauma. History of, or current catatonia or catatonia-like symptoms. History of, or current, malignancy. Current major or persistent depressive disorder (including bipolar depression). Significant, uncorrected visual or uncorrected hearing impairment. Allergy to strawberry. Positive pregnancy test Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study

Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NNZ-2591<br>NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks. | Drug: NNZ-2591<br>* NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.<br>* Other names: Cyclo-L-Glycyl-L-2-Allylproline;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591. | 13 weeks | 
| Pharmacokinetic - Measurement of Cmax | Maximum observed concentration (Cmax) of NNZ-2591 | 13 weeks | 
| Pharmacokinetic - Measurement of AUC | Area under the concentration-time curve of NNZ-2591 | 13 weeks | 
| Pharmacokinetic - Measurement of time to Cmax | Time to Cmax of NNZ-2591 | 13 weeks | 
| Pharmacokinetic - Measurement of t1/2 | Apparent terminal elimination half-life of NNZ-2591 | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exploratory efficacy measurement | Assessed by Pitt Hopkins syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I) | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Caregiver Impression of Improvement | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Pitt Hopkins syndrome-specific Clinical Global Impression Scales-Domain Improvement | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Pitt Hopkins syndrome-specific Clinical Global Impression Scale-Severity (CGI-S)-Overall and Domain | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Caregiver Top 3 Concerns Likert Scale | 13 weeks | 
| Exploratory efficacy measurement | Assessed by MacArthur-Bates Communicative Development Inventory (MB-CDI) | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Observer-Reported Communication Ability (ORCA) | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Aberrant Behavior Checklist-2 (ABC-2) | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Child Sleep Habits Questionnaire (CSHQ) | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Gastrointestinal Health Questionnaire (GIHQ) | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Vineland Adaptive Behavior Scales-3, Interview version | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Modified two-minute walk test | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Bayley Scales of Infant Development 4 (BSID 4) motor scale | 13 weeks | 
| Exploratory efficacy measurement | Caregiver Diaries | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Quality of Life Inventory-Disability (QI-Disability) | 13 weeks | 
| Exploratory efficacy measurement | Assessed by Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating | 13 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pitt Hopkins Syndrome