Studying the effects of deferiprone in Pelizaeus-Merzbacher disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

27 Dec 2024 → ongoing

Decision date (initial)

2024-12-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ZonMW

External identifiers

EU CT number

2024-511968-81-00

EudraCT number

2021-000070-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To evaluate the effect of deferiprone on gross motor function in children with PMD

Secondary objectives 3

1. To assess the effect of deferiprone on myelination and white matter integrity with quantitative brain MRI parameters, including Diffusion Tensor Imaging (DTI); Chemical Shift Imaging (CSI); Neurite Orientation Dispersion and Density Imaging (NODDI); Myelin Water Fraction Imaging (MWFI)
2. To assess the effect of deferiprone on clinical parameters: Health Utility Index (HUI); Manual Ability Classification System (MACS); Communication Function Classification System (CFCS); Eating and Drinking Ability Classification System (EDACS)
3. To assess the effect of deferiprone on functional CNS connectivity: EEG

Conditions and MedDRA coding

Pelizaeus-Merzbacher disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male whose age at screening is ≤ 8 years
2. Genetically proven PMD with a hemizygous clinically relevant missense mutation in the PLP1 gene or a PLP1 triplication (or higher copy numbers) and a brain MRI compatible with the diagnosis.
3. Lives within reasonable travel distance from Amsterdam.
4. Possibility of weekly capillary blood sampling at or close to home.
5. Connatal or classic form of the disease (defined as not being able to sit without support and/or a mutation predicting this form, e.g. PLP1 duplication or higher copy numbers; known missense mutations associated with severe forms).

Exclusion criteria 9

1. Patients with PLP1 duplications.
2. Iron deficiency
3. History of neutropenia in the last 12 months (absolute neutrophile count < 1.5 X 109/l)
4. Clinically asymptomatic
5. Comorbidity with another genetic defect, e.g. Down syndrome or other genetic disorders with impaired development.
6. Presence of an unrelated serious condition (e.g. developmental anomaly, significant cardiac, liver, blood or kidney disease or malignancy).
7. Participation in another clinical study with therapeutic intervention.
8. Unable to undergo MRI due to metal-containing implants, such as cochlea implant, neurostimulator or pacemaker.
9. Known allergy or hypersensitivity to deferiprone or to any of the other components of the formulation used in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Motor function as measured by the gross motor function measurement tool (GMFM-88). (Paulson and Vargus-Adams, 2017) and using the GMF scoring for metachromatic leukodystrophy, MLD-GMF score (Kehrer et al., 2011)

Secondary endpoints 3

1. Quantitative brain MRI parameters: Diffusion Tensor Imaging (DTI); Chemical Shift Imaging (CSI); Neurite Orientation Dispersion and Density Imaging (NODDI); Density Imaging (NODDI); Myelin Water Fraction Imaging (MWFI)
2. Electrophysiological parameters: EEG
3. Clinical parameters: General health and quality of life: Health Utility Index (HUI); Hand function: Manual Ability Classification System (MACS); Manual Ability Classification System (MACS); Communication Function Classification System (CFCS); Swallowing function: Eating and Drinking Ability Classification System (EDACS); Euro-Quality of Life Instrument 5D, 5 levels (EQ-5D-Y, proxy); Vineland Adaptive Behavior Scales, 3rd edition (Vineland-3)

Investigational products

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

Test 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

Prof. dr. N.I. Wolf

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Prof. dr. N.I. Wolf

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 5 files

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

Application history

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