Clinical trial NCT05025332: An Open-Label Study of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)
Official title: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pitt Hopkins Syndrome
Keywords: Pitt Hopkins Syndrome
Lead sponsor: Neuren Pharmaceuticals Limited
Sponsor class: INDUSTRY
First posted: 2021-08-27
Enrollment: 28
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability
timeFrame: 13 weeks
measure: Pharmacokinetic - Mean AUC24
timeFrame: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.
measure: Pharmacokinetic - t1/2
timeFrame: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.
Secondary outcomes:
measure: Pitt Hopkins Syndrome-specific Clinical Global Impression Scale (CGI-I) - Overall Improvement
timeFrame: CGI-I was assessed at weeks 6, 13/EOT & 15. Overall improvement scores relate to week 13/EOT visit.
measure: Caregiver Impression of Improvement: Overall Score
timeFrame: CIC was assessed at Week13/EOT
measure: Pitt Hopkins Syndrome-specific Clinical Global Impression Scale - Severity (CGI-S) - Overall Score
timeFrame: Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).
measure: Caregiver Top 3 Concerns
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in average concern severity.
measure: MacArthur-Bates Communicative Development Inventory (MB-CDI)
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13).
measure: Observer-Reported Communication Ability (ORCA)
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Score.
measure: Aberrant Behavior Checklist-2 (ABC-2)
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.
measure: CSHQ
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.
measure: GIHQ
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total frequency score.
measure: Vineland Adaptive Behavior Scales-3, Interview Version
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in composite standard score.
measure: Modified Two-minute Walk Test
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in distance travelled on two minute walk test.
measure: QI-Disability
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall score score.
measure: ICND
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall quality of life rating score.
measure: Behavior Problems Inventory - Short Form
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in Total Frequency score.
measure: Bayley Scales of Infant Development (BSID-4): Non Verbal Development Quotient (NVDQ)
timeFrame: Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in NVDQ score.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
Study officials:
affiliation: Neuren Pharmaceuticals
name: James Shaw
role: STUDY_DIRECTOR
References: