An Open-Label Phase 2a Study to Evaluate the Safety, Tolerability, and Efficacy of Vafidemstat in Adults with Phelan-McDermid Syndrome (PMS) (HOPE-2).
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Concomitant medication use.
研究概览
简要总结
To evaluate the safety and tolerability of vafidemstat in adults with PMS.
研究设计
- 分配方式
- Non Randomized
- 主要目的
- Hope-2
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- •Confirmed clinical diagnosis of PMS, supported by molecular evidence of a pathogenic SHANK3 point mutation or a deletion involving 22q13.3 that includes at least part of the SHANK3 gene. Molecular confirmation may be established using any conventional method, including chromosomal microarray analysis (CMA), chromosome structural tests (fluorescence in situ hybridization [FISH]/karyotype), or sequencing.
- •Aberrant Behaviour Checklist (ABC) - Irritability Subscale score equal or greater than 12 during the 4 weeks prior to Screening and confirmed at the Screening Visit (Visit 1).
- •Written informed consent must be obtained from the Participant, with the support measures required under Law 8/2021 to facilitate understanding and decision‑making. Only when the Participant is unable to provide valid informed consent may the Court-Appointed Representative provide consent on their behalf. In all cases, the Participant shall receive information about the study in a manner appropriate to their level of understanding.
- •The Participant must have a study Caregiver (e.g., Court-Appointed Representative, family member, social worker, residential facility staff, or nurse) who, in the Investigator’s judgment, has frequent and sufficient contact (e.g., spends at least 4 hours/week with the Participant) and can accompany the Participant during study visits, as well as provide accurate information about the Participant’s health.
排除标准
- •Failure to perform Screening procedures.
- •Participants who, in the opinion of the Investigator, are not suitable for inclusion in the trial or is unlikely to comply with the study protocol for any reason.
- •Participants with a DSM-5 diagnosis may be included provided that all of the following conditions are met: a) Symptoms of the comorbid condition have been clinically stable for at least 3 months prior to Screening. b) The comorbid condition is not an acute exacerbation and does not require immediate or intensive clinical management. c) No initiation or change in pharmacological or behavioural treatment for the comorbid condition is anticipated during the study period. d) In the Investigator’s opinion, the comorbid condition will not interfere with study participation, safety, or the assessment and reliability of study endpoints.
- •Clinically significant, advanced, or unstable disease that is likely to result in rapid deterioration of the Participant’s condition or affect their safety during the trial, including but not limited to: a) Respiratory insufficiency: the status must be determined as per usual clinical practice. b) Hepatic impairment (serum values of total bilirubin value, alanine aminotransferase, aspartate aminotransferase and/or gamma-glutamyl transferase > 2 times the upper limit of normal). c) Renal insufficiency (estimated glomerular filtration rate < 90 mL/min/1.73m2). d) Heart disease (myocardial infarction, unstable angina, heart failure class III or IV, cardiomyopathy onset) within 6 months before Screening Visit). e) Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg on 2 separate measurements taken at least 10 minutes apart. f) Atrioventricular block (type II/Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QT interval corrected using Fridericia's formula (QTcF) (males > 450 msec; and females > 470 msec), unless attributable to a right bundle branch block acquired from previous cardiac surgery or congenital heart disease. g) Uncontrolled diabetes (glycosylated haemoglobin [Hb1Ac] > 7.5%). h) Uncontrolled hypo- or hyperthyroidism at Screening, based on laboratory results. i) Platelets < 150,000/mm3 and/or neutrophils < 2,000/mm
- •j) Lifetime history of malignancy. k) Lifetime history of moderate‑to‑severe traumatic brain injury.
结局指标
主要结局
Concomitant medication use.
Concomitant medication use.
Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs), including Adverse Events of Special Interest (AESIs).
Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs), including Adverse Events of Special Interest (AESIs).
Number, frequency and severity of serious TEAEs, including AESIs.
Number, frequency and severity of serious TEAEs, including AESIs.
Number and percentage of withdrawn Participants due to TEAEs, including AESIs.
Number and percentage of withdrawn Participants due to TEAEs, including AESIs.
Frequency of clinically relevant abnormalities in physical examination findings, vital signs and ECG parameters.
Frequency of clinically relevant abnormalities in physical examination findings, vital signs and ECG parameters.
Frequency of clinical laboratory parameters (haematology and chemistry) of potential clinical concern.
Frequency of clinical laboratory parameters (haematology and chemistry) of potential clinical concern.
Number and percentage of Participants exhibiting suicidal ideation or behaviours, as evaluated by the Columbia - Suicide Severity Rating Scale (C-SSRS).
Number and percentage of Participants exhibiting suicidal ideation or behaviours, as evaluated by the Columbia - Suicide Severity Rating Scale (C-SSRS).
次要结局
- Change from Baseline (Visit 2) in the: - Aberrant Behaviour Checklist (ABC) Irritability Subscale. - Clinical Global Impression of Severity - Anger and Aggression (CGI-S A/A).
- Change from Baseline (Visit 2) in the: - Repetitive Behaviour Scale-Revised (RBS-R). - Phelan-McDermid Syndrome Assessment of Severity (PMSA-S). - ABC Subscales: o Stereotypic Behaviour. o Hyperactivity/Non-compliance. o Inappropriate Speech. o Social Withdrawal.
研究者
Director Clinical Operations
Scientific
Oryzon Genomics S.A.