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Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

Short name PTHS-001

NCTNCT05025332 (opens ClinicalTrials.gov in a new tab)Other idNEU-2591-PTHS-001
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 2
Enrollment
28 participants (actual)
Sponsor
Neuren Pharmaceuticals Limited · Industry
Design
Allocation not applicable · Open label (no masking)
Countries
1 country

United States

Start
14 Oct 2022
Primary completion
27 Feb 2024
Completion
3 May 2024
First posted
27 Aug 2021
Last update posted
18 Jun 2025
Conditions
Pitt Hopkins Syndrome

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2022202320242025
  1. Ph 2

    PTHS-001

    NCT05025332

    14 Oct 2022 to 3 May 2024

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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

Interventions

  • NNZ-2591Drug

Arms1

  • Experimental

    NNZ-2591

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

Primary outcomes3

Outcomes the sponsor listed as primary.

  1. Safety and Tolerability

    Time frame · 13 weeks

    Registry description

    To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.

  2. Pharmacokinetic - Mean AUC24

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

    Registry description

    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.

  3. Pharmacokinetic - t1/2

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

    Registry description

    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.

Secondary outcomes(15)

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

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

    Registry description

    Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement. Score on a Likert scale (1-7) where lower scores are better.

  2. Caregiver Impression of Improvement: Overall Score

    Time frame · CIC was assessed at Week13/EOT

    Registry description

    Caregiver Impression of Improvement: Overall Score. Measured on a 7 point Likert scale (1-7) where lower scores are better.

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

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

    Registry description

    Pitt Hopkins syndrome-specific Clinical Global Impression Scale - Severity (CGI-S) - Change from baselines on overall Score based on a 7 point Likert scale (1-7) where lower scores are better.

  4. Caregiver Top 3 Concerns

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

    Registry description

    Caregiver Top 3 Concerns: Change from baseline in Average Concern Severity. The average concern severity defined as the average of the severity scores for the three concerns evaluated at a given visit, and was calculated as long as at least one concern was useable for analysis at the visit. Scores range from 0 - 10 with higher scores indicating greater concern severity. A negative change from baseline indicates improvement.

  5. MacArthur-Bates Communicative Development Inventory (MB-CDI)

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

    Registry description

    MacArthur-Bates Communicative Development Inventory (MB-CDI): Words Understood Domain. Scores ranges from 0-396, with higher scores indicating greater language ability. A positive change from baseline indicates improvement.

  6. Observer-Reported Communication Ability (ORCA)

    Time frame · Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Score.

    Registry description

    Observer-Reported Communication Ability (ORCA): Change from baseline in Modified t-score. The ORCA measures an individual's communication abilities based on observations made by caregivers, parents, or other relevant observers, and is based on 4 domains: Expressive Communication, Receptive Communication, Social Communication, and Pragmatic Language Skills. Scores range from 25.8 - 83.8, with higher scores indicating greater communication ability. A positive change from baseline indicates improvement. A T-score standardizes the individual's performance relative to a normative sample. It typically has a mean of 50 and a standard deviation of 10. T score = 50 + 10 × (X-µ)/σ Where: X is the individual's raw score μ is the population mean σ is the standard deviation

  7. Aberrant Behavior Checklist-2 (ABC-2)

    Time frame · Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.

    Registry description

    Aberrant Behavior Checklist-2 (ABC-2): Change from baseline in Total Score. Range of scores is 0-174, with higher scores indicating more behavioral issues. A negative change from baseline indicates improvement.

  8. CSHQ

    Time frame · Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.

    Registry description

    Child Sleep Habits Questionnaire (CSHQ). Total Score. Change from baseline. Range of scores was (33-99) with higher scores being worse.

  9. GIHQ

    Time frame · Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total frequency score.

    Registry description

    Gastrointestinal Health Questionnaire (GIHQ). Change from baseline in total frequency score. Range of scores was (0-197) with higher scores being worse.

  10. Vineland Adaptive Behavior Scales-3, Interview Version

    Time frame · Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in composite standard score.

    Registry description

    Vineland Adaptive Behavior Scales-3 (VABS-3), Interview version, Change from baseline in Adaptive Behavior Composite Standard Score. Scores range from 20 - 140 with higher scores indicating greater functional abilities. A positive change from baseline indicates improvement.

  11. Modified Two-minute Walk Test

    Time frame · Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in distance travelled on two minute walk test.

    Registry description

    Modified two-minute walk test. Change from baseline in distance travelled (m) on 2 minute walk test. The test was only administered for participants who were ambulatory and able to complete the assessment. A positive score on change from baseline indicates improvement in distance walked.

  12. QI-Disability

    Time frame · Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall score score.

    Registry description

    Quality of Life Inventory-Disability (QI-Disability). Overall Score change from baseline. Scores range from 0 - 100 with higher scores indicating better quality of life. A positive change from baseline indicates improvement.

  13. ICND

    Time frame · Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall quality of life rating score.

    Registry description

    Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating, change from baseline. Score ranges from 1 - 6, with a higher score indicating better quality of life. A positive change from baseline indicates improvement.

  14. Behavior Problems Inventory - Short Form

    Time frame · Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Frequency score.

    Registry description

    Change from baseline in Behavior Problems Inventory - Short Form Total Frequency Score. Scores range from 0-120, with higher scores indicating greater frequency in behavior problems. A negative change from baseline indicates improvement.

  15. Bayley Scales of Infant Development (BSID-4): Non Verbal Development Quotient (NVDQ)

    Time frame · Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in NVDQ score.

    Registry description

    Change from baseline in Non Verbal Development Quotient (NVDQ). Scores range from 40 - 160, with higher scores indicating greater development. A positive change from baseline indicates improvement.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· 13 weeks

Safety and Tolerability

GroupValue (Participants)
NNZ-259115
Primary outcomeMean· Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

Pharmacokinetic - Mean AUC24

GroupValue (ug.h/mL)Spread
NNZ-259130556.1
Primary outcomeMean· Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

Pharmacokinetic - t1/2

GroupValue (hours)Spread
NNZ-25917.171.64
Secondary and other outcome results(5)
Secondary outcomeMean· CGI-I was assessed at weeks 6, 13/EOT & 15. Overall improvement scores relate to week 13/EOT visit.

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

GroupValue (score on a scale)Spread
Modified Intention to Treat2.60.92
Secondary outcomeMean· CIC was assessed at Week13/EOT

Caregiver Impression of Improvement: Overall Score

GroupValue (score on a scale)Spread
Modified Intention to Treat3.01.00
Secondary outcomeMean· Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).

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

GroupValue (score on a scale)Spread
Modified Intention to Treat-0.50.52
Secondary outcomeMean· Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in average concern severity.

Caregiver Top 3 Concerns

GroupValue (score on a scale)Spread
Modified Intention to Treat-1.6061.5385
Secondary outcomeMean· Change from baseline (visit 3, week 0) to visit 16/EOT (week 13).

MacArthur-Bates Communicative Development Inventory (MB-CDI)

GroupValue (score on a scale)Spread
Modified Intention to Treat15.942.07

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
NNZ-2591All enrolled participants who received at least one dose of IMP0 / 160 / 1615 / 16

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 3 Years up to 17 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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. 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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