Pitt Hopkins Syndrome
Conditions
Keywords
Pitt Hopkins Syndrome
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.
Interventions
DRUGNNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
Sponsors
Neuren Pharmaceuticals Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 - Mean AUC24 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement. Score on a Likert scale (1-7) where lower scores are better. |
| Caregiver Impression of Improvement: Overall Score | CIC was assessed at Week13/EOT | Caregiver Impression of Improvement: Overall Score. Measured on a 7 point Likert scale (1-7) where lower scores are better. |
| 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). | 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. |
| Caregiver Top 3 Concerns | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in average concern severity. | 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. |
| MacArthur-Bates Communicative Development Inventory (MB-CDI) | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13). | 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. |
| Observer-Reported Communication Ability (ORCA) | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Score. | 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 |
| Aberrant Behavior Checklist-2 (ABC-2) | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score. | 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. |
| CSHQ | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score. | Child Sleep Habits Questionnaire (CSHQ). Total Score. Change from baseline. Range of scores was (33-99) with higher scores being worse. |
| GIHQ | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total frequency score. | Gastrointestinal Health Questionnaire (GIHQ). Change from baseline in total frequency score. Range of scores was (0-197) with higher scores being worse. |
| Vineland Adaptive Behavior Scales-3, Interview Version | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in composite standard score. | 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. |
| Modified Two-minute Walk Test | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in distance travelled on 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. |
| QI-Disability | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall score score. | 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. |
| ICND | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall quality of life rating score. | 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. |
| Behavior Problems Inventory - Short Form | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Frequency score. | 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. |
| Bayley Scales of Infant Development (BSID-4): Non Verbal Development Quotient (NVDQ) | Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in NVDQ score. | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited based on physician referral at 5 academic medical centers between August 2022 and December 2023
Pre-assignment details
Following completion of informed consent, participants (28) underwent 4 weeks of baselining/screening. During this process 12 participants failed screening. The remaining 16 participants commenced treatment.
Participants by arm
| Arm | Count |
|---|---|
| NNZ-2591 All participants who successfully completed 4 week post consent screening period. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Screening | Screen failure | 12 |
| Treatment & Follow Up | Adverse Event | 4 |
| Treatment & Follow Up | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | NNZ-2591 |
|---|---|
| Age, Categorical <=18 years | 16 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 9.1 years STANDARD_DEVIATION 4.63 |
| Autism Mental Status Exam | 9.96 score on a scale STANDARD_DEVIATION 2.29 |
| Body Mass Index (kg/m^2) | 16.846 kg/m^2 STANDARD_DEVIATION 2.0979 |
| BSID-4 NVDQ | 11.602 score on a scale STANDARD_DEVIATION 7.3599 |
| Clinical Global Impression of Severity (CGI-S) | 5.0 units on a scale STANDARD_DEVIATION 0.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height (cm) | 127.26 centimetres STANDARD_DEVIATION 22.609 |
| History of Developmental Regression No | 15 Participants |
| History of Developmental Regression Yes | 1 Participants |
| Presence of Co-morbid Psychiatric Disorders Attention Deficit Disorder | 1 participants |
| Presence of Co-morbid Psychiatric Disorders Autism Spectrum Disorder | 7 participants |
| Presence of Co-morbid Psychiatric Disorders BiPolar Disorder | 0 participants |
| Presence of Co-morbid Psychiatric Disorders Obsessive Compulsive Disorder | 0 participants |
| Presence of Co-morbid Psychiatric Disorders Other | 4 participants |
| PTHS variant Complex | 0 participants |
| PTHS variant Conversion | 0 participants |
| PTHS variant Deletion | 6 participants |
| PTHS variant Deletion-Insertion | 0 participants |
| PTHS variant Duplication | 0 participants |
| PTHS variant Frameshift variant | 2 participants |
| PTHS variant Insertion | 0 participants |
| PTHS variant Inversion | 0 participants |
| PTHS variant Missense variant | 2 participants |
| PTHS variant Nonsense variant | 3 participants |
| PTHS variant Other | 2 participants |
| PTHS variant Substitution | 5 participants |
| PTHS variant Unknown | 1 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants |
| Race/Ethnicity, Customized White | 11 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
| Weight (kg) | 28.57 kilograms STANDARD_DEVIATION 12.291 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 15 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
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.
Population: All participants enrolled in this study who receive the study drug through to the morning dose of Week 2 (Visit 5) as a minimum, and who underwent PK sample collection at least one of the specified post-dose time point(s).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Pharmacokinetic - Mean AUC24 | 305 ug.h/mL | Standard Deviation 56.1 |
Primary
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.
Population: All participants enrolled in this study who receive the study drug through to the morning dose of Week 2 (Visit 5) as a minimum, and who undergo PK sample collection at least one of the specified post-dose time point(s).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Pharmacokinetic - t1/2 | 7.17 hours | Standard Deviation 1.64 |
Primary
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
Population: Safety population - all participants receiving at least one dose of NNZ-2591
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NNZ-2591 | Safety and Tolerability | Participants with TEAE | 15 Participants |
| NNZ-2591 | Safety and Tolerability | Participants with Serious TEAE | 0 Participants |
| NNZ-2591 | Safety and Tolerability | Participants who discontinued due to TEAE | 4 Participants |
| NNZ-2591 | Safety and Tolerability | Participants with mild TEAE as highest intensity | 12 Participants |
| NNZ-2591 | Safety and Tolerability | Participants with moderate TEAE as highest intensity | 3 Participants |
| NNZ-2591 | Safety and Tolerability | Participants with severe TEAE as highest intensity | 0 Participants |
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Aberrant Behavior Checklist-2 (ABC-2) | -4.8 score on a scale | Standard Deviation 14.15 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.3203Wilcoxon Signed rank
Secondary
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.
Population: Standard domain scores only calculated for participants 42 months of age and younger.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Bayley Scales of Infant Development (BSID-4): Non Verbal Development Quotient (NVDQ) | 0.444 score on a scale | Standard Deviation 2.4685 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.2402Wilcoxon Signed rank
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Behavior Problems Inventory - Short Form | 3.2 score on a scale | Standard Deviation 15.45 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.7695Wilcoxon Signed rank
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Caregiver Impression of Improvement: Overall Score | 3.0 score on a scale | Standard Deviation 1 |
Comparison: Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participants.p-value: 0.0234Wilcoxon Signed rank
Secondary
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.
Population: Modified intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Caregiver Top 3 Concerns | -1.606 score on a scale | Standard Deviation 1.5385 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.0039Wilcoxon Signed rank
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | CSHQ | 0.4 score on a scale | Standard Deviation 1.79 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.3574Wilcoxon Signed rank
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | GIHQ | -6.3 score on a scale | Standard Deviation 21.83 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.4131Wilcoxon Signed rank
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | ICND | 0.5 score on a scale | Standard Deviation 1.44 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.375Wilcoxon Signed rank
Secondary
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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | MacArthur-Bates Communicative Development Inventory (MB-CDI) | 15.9 score on a scale | Standard Deviation 42.07 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.1934Wilcoxon Signed rank
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Modified Two-minute Walk Test | 8.704 meters | Standard Deviation 25.7178 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 1Wilcoxon Signed rank
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Observer-Reported Communication Ability (ORCA) | 1.97 T-score | Standard Deviation 8.963 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.748Wilcoxon Signed rank
Secondary
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.
Population: Modified intention to treat (MITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement | 2.6 score on a scale | Standard Deviation 0.92 |
Comparison: Descriptive statistics were used to summarize the data. For total scores, waterfall plots and histograms/bar charts were created at the EOT visit with plots for all participants.p-value: 0.0039Wilcoxon Signed rank
Secondary
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).
Population: Modified intention to treat (MITT) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Pitt Hopkins Syndrome-specific Clinical Global Impression Scale - Severity (CGI-S) - Overall Score | -0.5 score on a scale | Standard Deviation 0.52 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.0313Wilcoxon Signed rank
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | QI-Disability | -1.672 score on a scale | Standard Deviation 9.8493 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.7002Wilcoxon Signed rank
Secondary
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.
Population: one participant completed baseline VABS-3 but did not complete VABS-3 at EOT visit. Hence number analysed is only 10.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Vineland Adaptive Behavior Scales-3, Interview Version | 0.0 score on a scale | Standard Deviation 2.36 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period.p-value: 0.9063Wilcoxon Signed rank