Clemastine fumarate for Pitt-Hopkins syndrome

Inclusion criteria

• {"criterion_text":"- A molecularly confirmed diagnosis of PTHS according to the criteria described in the 2019 consensus statement.(Zollino et al. 2019)\n- An age of at least 1.0 years old at the start of the trial.\n- A bodyweight of at least 12.0 kilograms at the start of the trial.\n- Ability of the parents or legally designated representative of the subject to understand the information about trial procedures and requirements.\n- Ability and willingness of the parents or legally designated representative to provide written informed consent for trial participation."}

Exclusion criteria

• {"criterion_text":"- Comorbidity with any other relevant disease or condition, including a second neurodevelopmental disorder in addition to PTHS, that would impair assessment of treatment effects (judged on a case by case basis by the principal investigator).\n- Simultaneous involvement in another study protocol without prior approval\n- Non-incidental use of clemastine in the 6 months prior to the start of the trial\n- Non-incidental use of medication currently being investigated in remyelination trials, including but not limited to domperidone, liothyronine, quetiapine, testosterone and bazedoxifene, in the 6 months prior to the start of the trial.\n- Any change in use or dosage of psychotropic medications during the 4 weeks prior to the start of the trial.\n- Contraindications for use of clemastine, such as known porphyria or hypersensitivity to clemastine or any of the excipients.\n- Non-incidental use and planned continuation of CNS depressants including but not limited to hypnotics, anxiolytics, monoamine-oxidase inhibitors, tricyclic antidepressants, opioid analgesics, other antihistamines with sedating properties (e.g. promethazine) and anticholinergic medication."}

Primary endpoints

• {"endpoint_text":"- Caretaker Global Impression rating scale (CaGI)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Clinical Global Impression rating scale (CGI)\n- PROMIS Custom Short Form – Fatigue; Numeric Rating Scale (NRS) – Fatigue\n- Aberrant Behavior Checklist; EuroQol-5D-Y-5L; PROMIS Early Childhood Parent Report v1.0 – Child-Caregiver Interactions; PROMIS Early Childhood Parent Report v1.0 – Anxiety; PROMIS Early Childhood Parent Report v1.0 – Depressive Symptoms\n- PROMIS Early Childhood Parent Report v1.0 - Sleep disturbance; Numeric Rating Scale (NRS) – Sleep; Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms questionnaire, ‘stomach pain and hurt’, ‘heart burn and reflux’, ‘gas and bloating’, and ‘constipation’ scales; Rett-syndrome Behavior Questionnaire, Breathing Problems (RSBQ-BP), adapted for PTHS ;Number and type of epileptic seizures during past 30 days\n- Gross Motor Function Measure (GMFM-88); Two minute walking test\n- Resting-state electroencephalography (EEG) recording: power spectrum, long term temporal correlations and network level excitation-inhibition dynamics\n- Pharmacokinetic parameters such as maximum concentration (Cmax), area under the concentration-time curve (AUC), half-life and predicted trough concentration (Ctrough) at steady state, using nonlinear mixed effects modelling (NONMEM).\n- IMTA Medical Consumption Questionnaire (iMCQ); IMTA Productivity Cost Questionnaire (iPCQ)\n- Semi-structured, qualitative interviews\n- The relationship between clemastine PK and safety/efficacy-related biomarkers","definition_or_measurement_approach":"CGI/CaGI: caregiver- and clinician-rated global impression scales; PROMIS/PedsQL/ABC/EuroQol/RSBQ: standardised validated questionnaires/scales as listed; EEG: resting-state recordings with analysis of power spectrum, long term temporal correlations and network-level excitation-inhibition metrics; PK: Cmax, AUC, half-life and Ctrough at steady state analysed using nonlinear mixed effects modelling (NONMEM); health economics: iMCQ and iPCQ questionnaires; qualitative data collected via semi-structured interviews."}

Netherlands

Earliest CTIS Part Ii Submission Date

18-02-2026

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

54

Number Of Sites

1

Number Of Participants

40

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands