A randomized, placebo-controlled trial to assess the efficacy, tolerability, and pharmacokinetics of clemastine in children and adults with Pitt-Hopkins syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-04-13

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacokinetic, Pharmacodynamic

To assess the overall treatment effects of clemastine in PTHS, according to caretakers

Secondary objectives 10

1. To assess the overall treatment effects of clemastine in PTHS, according to investigators
2. To assess the tolerability of clemastine in PTHS
3. To assess the effects of clemastine on behavior and wellbeing in PTHS
4. To assess the effects of clemastine on physical complaints in PTHS
5. To assess the effects of clemastine on motor function in PTHS
6. To assess the neurophysiological effects of clemastine in PTHS
7. To validate a translational pharmacokinetic/pharmacodynamic (PKPD)-model of clemastine in patients with PTHS
8. To perform a health technology assessment (HTA) including trial- and model-based cost-effectiveness analyses (CEA)
9. To assess the expectations of and experiences with clemastine of parents/caretakers of individuals with PTHS
10. To perform exploratory PK/PD analyses

Conditions and MedDRA coding

Pitt-Hopkins syndrome

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. A molecularly confirmed diagnosis of PTHS according to the criteria described in the 2019 consensus statement.(Zollino et al. 2019)
2. An age of at least 1.0 years old at the start of the trial.
3. A bodyweight of at least 12.0 kilograms at the start of the trial.
4. Ability of the parents or legally designated representative of the subject to understand the information about trial procedures and requirements.
5. Ability and willingness of the parents or legally designated representative to provide written informed consent for trial participation.

Exclusion criteria 7

1. 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).
2. Simultaneous involvement in another study protocol without prior approval
3. Non-incidental use of clemastine in the 6 months prior to the start of the trial
4. 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.
5. Any change in use or dosage of psychotropic medications during the 4 weeks prior to the start of the trial.
6. Contraindications for use of clemastine, such as known porphyria or hypersensitivity to clemastine or any of the excipients.
7. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Caretaker Global Impression rating scale (CaGI)

Secondary endpoints 10

1. Clinical Global Impression rating scale (CGI)
2. PROMIS Custom Short Form – Fatigue; Numeric Rating Scale (NRS) – Fatigue
3. 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
4. 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
5. Gross Motor Function Measure (GMFM-88); Two minute walking test
6. Resting-state electroencephalography (EEG) recording: power spectrum, long term temporal correlations and network level excitation-inhibition dynamics
7. 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).
8. IMTA Medical Consumption Questionnaire (iMCQ); IMTA Productivity Cost Questionnaire (iPCQ)
9. Semi-structured, qualitative interviews
10. The relationship between clemastine PK and safety/efficacy-related biomarkers

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Leonie Menke

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Leonie Menke

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications