A Phase 2 interventional study of NNZ-2591 in Pitt Hopkins Syndrome, sponsored by Neuren Pharmaceuticals Limited. Completed at 5 sites in United States. Open to participants aged 3 Years to 17 Years. Per ClinicalTrials.gov, last updated 2025-06-18.
Sponsored by Neuren Pharmaceuticals Limited · Phase 2, Interventional, and Treatment
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Pitt Hopkins Syndrome.
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.
Neuren Pharmaceuticals Limited is the lead sponsor of 15 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
Drug: NNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
Also known as: Cyclo-L-Glycyl-L-2-Allylproline
Safety and Tolerability
To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
Time frame: 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.
Time frame: 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.
Time frame: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.
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.
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
Caregiver Impression of Improvement: Overall Score. Measured on a 7 point Likert scale (1-7) where lower scores are better.
Time frame: 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.
Time frame: 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.
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)
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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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.
Time frame: 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.
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
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.
Time frame: 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.
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
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.
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)
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.
Time frame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in NVDQ score.
Participants were recruited based on physician referral at 5 academic medical centers between August 2022 and December 2023
| Milestone | NNZ-2591 |
|---|---|
| Started | 28 |
| Completed | 16 |
| Not completed | 12 |
| Withdrew: Screen failure | 12 |
| Milestone | NNZ-2591 |
|---|---|
| Started | 16 |
| Completed | 11 |
| Not completed | 5 |
| Withdrew: Protocol violation | 1 |
| Withdrew: Adverse event | 4 |
To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
| Participants | NNZ-2591 |
|---|---|
| Participants with TEAE | 15 |
| Participants with Serious TEAE | 0 |
| Participants who discontinued due to TEAE | 4 |
| Participants with mild TEAE as highest intensity | 12 |
| Participants with moderate TEAE as highest intensity | 3 |
| Participants with severe TEAE as highest intensity | 0 |
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.
| ug.h/mL | NNZ-2591 |
|---|---|
| Pharmacokinetic - Mean AUC24 | 305 ± 56.1 |
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.
| hours | NNZ-2591 |
|---|---|
| Pharmacokinetic - t1/2 | 7.17 ± 1.64 |
Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement. Score on a Likert scale (1-7) where lower scores are better.
| score on a scale | Modified Intention to Treat |
|---|---|
| Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement | 2.6 ± 0.92 |
Caregiver Impression of Improvement: Overall Score. Measured on a 7 point Likert scale (1-7) where lower scores are better.
| score on a scale | Modified Intention to Treat |
|---|---|
| Caregiver Impression of Improvement: Overall Score | 3.0 ± 1.00 |
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.
| score on a scale | Modified Intention to Treat |
|---|---|
| Pitt Hopkins Syndrome-specific Clinical Global Impression Scale - Severity (CGI-S) - Overall Score | -0.5 ± 0.52 |
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.
| score on a scale | Modified Intention to Treat |
|---|---|
| Caregiver Top 3 Concerns | -1.606 ± 1.5385 |
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.
| score on a scale | Modified Intention to Treat |
|---|---|
| MacArthur-Bates Communicative Development Inventory (MB-CDI) | 15.9 ± 42.07 |
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
| T-score | Modified Intention to Treat |
|---|---|
| Observer-Reported Communication Ability (ORCA) | 1.97 ± 8.963 |
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.
| score on a scale | Modified Intention to Treat |
|---|---|
| Aberrant Behavior Checklist-2 (ABC-2) | -4.8 ± 14.15 |
Child Sleep Habits Questionnaire (CSHQ). Total Score. Change from baseline. Range of scores was (33-99) with higher scores being worse.
| score on a scale | Modified Intention to Treat |
|---|---|
| CSHQ | 0.4 ± 1.79 |
Gastrointestinal Health Questionnaire (GIHQ). Change from baseline in total frequency score. Range of scores was (0-197) with higher scores being worse.
| score on a scale | Modified Intention to Treat |
|---|---|
| GIHQ | -6.3 ± 21.83 |
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.
| score on a scale | Modified Intention to Treat |
|---|---|
| Vineland Adaptive Behavior Scales-3, Interview Version | 0.0 ± 2.36 |
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.
| meters | Modified Intention to Treat |
|---|---|
| Modified Two-minute Walk Test | 8.704 ± 25.7178 |
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.
| score on a scale | Modified Intention to Treat |
|---|---|
| QI-Disability | -1.672 ± 9.8493 |
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.
| score on a scale | Modified Intention to Treat |
|---|---|
| ICND | 0.5 ± 1.44 |
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.
| score on a scale | Modified Intention to Treat |
|---|---|
| Behavior Problems Inventory - Short Form | 3.2 ± 15.45 |
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.
| score on a scale | Modified Intention to Treat |
|---|---|
| Bayley Scales of Infant Development (BSID-4): Non Verbal Development Quotient (NVDQ) | 0.444 ± 2.4685 |
Collected over 15 weeks for each participant starting on the day of first dosing. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| NNZ-2591 | 0/16 (0%) | 0/16 (0%) | 15/16 (93.8%) |
| Event | NNZ-2591 |
|---|---|
| DiarrheaGastrointestinal disorders | 4/16 |
| FatigueGeneral disorders | 4/16 |
| ConstipationGastrointestinal disorders | 3/16 |
| NasopharyngitisInfections and infestations | 3/16 |
| VomitingGastrointestinal disorders | 2/16 |
| SomnolenceNervous system disorders | 2/16 |
| IrritabilityPsychiatric disorders | 2/16 |
| ContusionInjury, poisoning and procedural complications | 2/16 |
| Gastroenteritis - viralInfections and infestations | 2/16 |
| CoughRespiratory, thoracic and mediastinal disorders | 2/16 |
| Age, Categorical(Participants) | NNZ-2591 |
|---|---|
| <=18 years | 16 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Age, Continuous(years) | NNZ-2591 |
|---|---|
| Mean | 9.1 ± 4.63 |
| Sex: Female, Male(Participants) | NNZ-2591 |
|---|---|
| Female | 8 |
| Male | 8 |
| Ethnicity (NIH/OMB)(Participants) | NNZ-2591 |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 15 |
| Unknown or Not Reported | 0 |
| Race/Ethnicity, Customized(Participants) | NNZ-2591 |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 3 |
| Black or African American | 1 |
| Native Hawaiian or other Pacific Islander | 0 |
| White | 11 |
| Other | 1 |
| Multiple | 0 |
| Unknown | 0 |
| Clinical Global Impression of Severity (CGI-S)(units on a scale) | NNZ-2591 |
|---|---|
| Mean | 5.0 ± 0.69 |
| Height (cm)(centimetres) | NNZ-2591 |
|---|---|
| Mean | 127.26 ± 22.609 |
| Weight (kg)(kilograms) | NNZ-2591 |
|---|---|
| Mean | 28.57 ± 12.291 |
6 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Oct 2022 to primary completion in Feb 2024, 16 months.
Results were first posted in May 2025, 1 year 2 months after primary completion.
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Studies of the drug tested here: Ercanetide
Pitt-Hopkins syndrome
Neuren Pharmaceuticals Limited