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

Phase 2

Completed

• Conditions: Pitt Hopkins Syndrome
• Interventions: Drug: NNZ-2591

• Registration Number: NCT05025332
• Lead Sponsor: Neuren Pharmaceuticals Limited

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.

Study Timeline

• Study First Submitted: 2021-08-24
• Study First Submitted QC: 2021-08-24
• Study First Posted: 2021-08-27
• Study Start: 2022-10-14
• Primary Completion: 2024-02-27
• Study Completion: 2024-05-03
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-06
• Last Update Posted: 2024-08-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. Clinical diagnosis of PTHS with a documented disease-causing genetic etiology for the disorder.
2. Males or females aged 3-17 years.
3. Body weight of 12kg or higher at screening
4. Subjects with a Clinical Global Impression- Severity (CGI-S) score of 4 or greater at the Screening visit.
5. 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
6. Each subject must be able to swallow the study medication provided as a liquid solution.
7. Caregiver(s) must have sufficient English language skills.

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Exclusion Criteria

1. Body weight <12kg at screening
2. Clinically significant abnormalities in safety laboratory tests and vital signs at Screening.
3. Abnormal QTcF interval or prolongation at Screening.
4. Any other clinically significant finding on ECG at the Screening visit.
5. Positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and previous COVID 19 infection with last 12 months that required hospitalization.
6. Unstable or changes Psychotropic treatment 2 weeks prior to screening
7. Excluded concomitant treatments.
8. Actively undergoing regression or loss of skills.
9. Unstable seizure profile.
10. Current clinically significant renal conditions and abnormalities
11. Current clinically significant cardiovascular, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically significant organ impairment.
12. 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.
13. Has planned surgery during the study.
14. History of, or current, cerebrovascular disease or brain trauma.
15. History of, or current catatonia or catatonia-like symptoms.
16. History of, or current, malignancy.
17. Current major or persistent depressive disorder (including bipolar depression).
18. Significant, uncorrected visual or uncorrected hearing impairment.
19. Allergy to strawberry.
20. Positive pregnancy test
21. Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NNZ-2591	NNZ-2591	NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Exploratory efficacy measurement	13 weeks	Assessed by Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating

Trial Locations

Locations (5)

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

University of California at San Francisco; 🇺🇸 San Francisco, California, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

UT Southwestern; 🇺🇸 Dallas, Texas, United States