Pitt Hopkins SyndromePhase 2PTHS-001NCT05025332
An Open-Label Study of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)
A Phase 2 study testing NNZ-2591 in people with Pitt Hopkins Syndrome, run by Neuren Pharmaceuticals Limited at 5 sites in United States.
Trial summary
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Pitt Hopkins Syndrome. Read more about this study
- Who is it for?
- Ages 3 to 17 years
- Conditions the study is for
- Pitt Hopkins Syndrome
- What is being tested?
- NNZ-2591
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 5 sitesUnited States
- Study dates
- 14 Oct 2022to 3 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Rush University Medical Center
Chicago, Illinois, 60612
UT Southwestern
Dallas, Texas, 75390
University of California at San Francisco
San Francisco, California, 94143
About this study
Official title: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Pitt Hopkins Syndrome.
Read the 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.
- Conditions
- Pitt Hopkins Syndrome
- Being tested
- NNZ-2591
- Keywords
- Pitt Hopkins Syndrome
- Medical subject headings
- Pitt-Hopkins syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NNZ-2591Drug
Also called Cyclo-L-Glycyl-L-2-Allylproline
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
| Study group | Role | What they receive |
|---|---|---|
| NNZ-2591 | Experimental | NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks. Receives: Drug: NNZ-2591 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
Measured: 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.
Measured: 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.
Measured: 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
Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement. Score on a Likert scale (1-7) where lower scores are better.
Measured: 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
Caregiver Impression of Improvement: Overall Score. Measured on a 7 point Likert scale (1-7) where lower scores are better.
Measured: CIC was assessed at Week13/EOT
Pitt Hopkins Syndrome-specific Clinical Global Impression Scale - Severity (CGI-S) - Overall Score
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.
Measured: Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).
Caregiver Top 3 Concerns
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.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in average concern severity.
MacArthur-Bates Communicative Development Inventory (MB-CDI)
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.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13).
Observer-Reported Communication Ability (ORCA)
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
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Score.
Aberrant Behavior Checklist-2 (ABC-2)
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.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.
CSHQ
Child Sleep Habits Questionnaire (CSHQ). Total Score. Change from baseline. Range of scores was (33-99) with higher scores being worse.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.
GIHQ
Gastrointestinal Health Questionnaire (GIHQ). Change from baseline in total frequency score. Range of scores was (0-197) with higher scores being worse.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total frequency score.
Vineland Adaptive Behavior Scales-3, Interview Version
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.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in composite standard score.
Modified Two-minute Walk Test
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.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in distance travelled on two minute walk test.
QI-Disability
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.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall score score.
ICND
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.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall quality of life rating score.
Behavior Problems Inventory - Short Form
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.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Frequency score.
Bayley Scales of Infant Development (BSID-4): Non Verbal Development Quotient (NVDQ)
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.
Measured: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in NVDQ score.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2021
- Study start14 Oct 2022
- Primary completion27 Feb 2024
- Study completion3 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pitt Hopkins SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuren Pharmaceuticals Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James Shaw, Study director, Neuren Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05025332
- Sponsor's protocol ID
- NEU-2591-PTHS-001
- Acronym
- PTHS-001
- Status last verified
- Jun 2025
- First submitted
- 24 Aug 2021
- Last updated
- 18 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)
- ClinicalTrials.gov ID
- NCT05025332
- Acronym / sponsor ID
- PTHS-001 / NEU-2591-PTHS-001
- Conditions
- Pitt Hopkins Syndrome
- Keywords
- Pitt Hopkins Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Neuren Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
- Study start
- 14 Oct 2022 (actual)
- Primary completion
- 27 Feb 2024 (actual)
- Study completion
- 3 May 2024 (actual)
- First posted
- 27 Aug 2021 (actual)
- Results
- Posted 18 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NNZ-2591 | Experimental | Drug: NNZ-2591NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks. |
Who may qualify
- Ages
- 3 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NNZ-2591Also: Cyclo-L-Glycyl-L-2-AllylprolineNNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks. | Drug | NNZ-2591 |
Primary outcome
Safety and Tolerability
Time frame: 13 weeks
To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
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.
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.
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.
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.
15 secondary outcomes
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.
Caregiver Impression of Improvement: Overall Score
Time frame: CIC was assessed at Week13/EOT
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).
Caregiver Top 3 Concerns
Time frame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in average concern severity.
MacArthur-Bates Communicative Development Inventory (MB-CDI)
Time frame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13).
Observer-Reported Communication Ability (ORCA)
Time frame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Score.
Aberrant Behavior Checklist-2 (ABC-2)
Time frame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.
CSHQ
Time frame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.
GIHQ
Time frame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total frequency score.
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.
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.
QI-Disability
Time frame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall score score.
ICND
Time frame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall quality of life rating score.
Behavior Problems Inventory - Short Form
Time frame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Frequency score.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Shaw study director
Neuren Pharmaceuticals
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NNZ-2591 in people with Pitt Hopkins Syndrome, run by Neuren Pharmaceuticals Limited at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability (time frame: 13 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2025.