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

NCT05025332 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NEU-2591-PTHS-001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

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.

Conditions

Pitt Hopkins Syndrome

Keywords

Pitt Hopkins Syndrome

Outcome Measures

Primary Outcomes (3)

• 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 - Mean AUC24

  Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.

  Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

• Pharmacokinetic - t1/2

  Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.

  Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

Secondary Outcomes (15)

• Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement

  CGI-I was assessed at weeks 6, 13/EOT & 15. Overall improvement scores relate to week 13/EOT visit.

• Caregiver Impression of Improvement: Overall Score

  CIC was assessed at Week13/EOT

• Pitt Hopkins Syndrome-specific Clinical Global Impression Scale - Severity (CGI-S) - Overall Score

  Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).

• Caregiver Top 3 Concerns

  Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in average concern severity.

• MacArthur-Bates Communicative Development Inventory (MB-CDI)

  Change from baseline (visit 3, week 0) to visit 16/EOT (week 13).

Study Arms (1)

NNZ-2591

EXPERIMENTAL

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

Drug: NNZ-2591

Interventions

NNZ-2591 DRUG

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

Also known as: Cyclo-L-Glycyl-L-2-Allylproline

NNZ-2591

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neuren Pharmaceuticals Limited: lead

Study Sites (5)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California at San Francisco

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Pitt-Hopkins syndrome

Interventions

cyclo-L-glycyl-L-2-allylproline

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Neuren Pharmaceuticals

MedicalInformation@neurenpharma.com

+61 (3) 9092 0480

Study Officials

• James Shaw

  Neuren Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: August 27, 2021
• Study Start: October 14, 2022
• Primary Completion: February 27, 2024
• Study Completion: May 3, 2024
• Last Updated: June 18, 2025
• Results First Posted: May 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)