An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 5
- 主要终点
- Safety and Tolerability
研究概览
简要总结
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Pitt Hopkins Syndrome.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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
研究组 & 干预措施
NNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
干预措施: NNZ-2591 (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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.)
- Caregiver Impression of Improvement: Overall Score(CIC was assessed at Week13/EOT)
- 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).)
- Caregiver Top 3 Concerns(Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in average concern severity.)
- MacArthur-Bates Communicative Development Inventory (MB-CDI)(Change from baseline (visit 3, week 0) to visit 16/EOT (week 13).)
- Observer-Reported Communication Ability (ORCA)(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 (visit 3, week 0) to visit 16/EOT (week 13) in total score.)
- CSHQ(Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total score.)
- GIHQ(Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in total frequency score.)
- Vineland Adaptive Behavior Scales-3, Interview Version(Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in composite standard score.)
- 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.)
- QI-Disability(Change from baseline (visit 3, week 0) to visit 16/EOT (week 13) in overall score score.)
- ICND(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 (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 (visit 3, week 0) to visit 16/EOT (week 13) in NVDQ score.)