Clemastine fumarate as remyelinating treatment in internuclear ophthalmoparesis and multiple sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

30 Aug 2022 → 15 Aug 2025

Decision date (initial)

2024-08-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513099-17-00

EudraCT number

2021-003677-66

ClinicalTrials.gov

NCT05338450

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Our primary objective is to longitudinally evaluate the efficacy of clemastine fumarate to reduce dysconjugacy of horizontal eye movements measured by infrared oculography in patients with MS and internuclear ophthalmoplegia (INO) and to evaluate whether effects meaningfully persist after treatment, representing lasting remyelination.

Conditions and MedDRA coding

Internuclear ophthalmoparesis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. A clinically definite diagnosis of multiple sclerosis
2. Diagnosis of internuclear ophthalmoplegia determined by the first infrared oculography at screening with either cut-off of 1.174 of the versional dysconjugacy index area under the curve (VDI-AUC) of 15° saccades or 1.180 of the versional dysconjugacy index peak velocity/saccadic amplitude (VDI-PV/Am) of 15° saccades.
3. Age 18-70 (inclusive)
4. Use of disease modifying therapies is not a contraindication
5. Ability to understand the purpose and risks of the study and provide signed and dated informed consent

Exclusion criteria 19

1. Changes in immunomodulatory therapy for multiple sclerosis in the 6 months before inclusion into the study
2. Clinical relapse of MS or high dosage corticosteroid use within 30 days before inclusion into the study.
3. Contraindications to clemastine use, such as known porphyria or hypersensitivity to clemastine, other antihistamines with a similar chemical structure or any of the excipients.
4. Contraindications to fampridine use, such as hypersensitivity to fampridine or any of the excipients, history of epilepsy, kidney disease (GFR <50 ml/min absolute contraindication; GFR = 50-80 ml/min relative contraindication), use of Organic Cation Transporter 2 (OCT2) inhibitors or history of significant cardiac arrhythmias or conduction block.
5. Concomitant use of Fampridine or any other formulation of 4- aminopyridine (4AP) or diamino4ap that cannot be temporarily suspended prior to each study visit.
6. Changes in the use of medication currently being investigated in remyelination trials within 6 months before screening, including but not limited to domperidone, liothyronine, quetiapine, testosterone and bazedoxifene.
7. Non-incidental use of central nervous system depressants including but not limited to hypnotics, anxiolytics, monoamine-oxidase inhibitors (MAOI'S), tricyclic antidepressants, opioid analgesics and other antihistamines with sedating properties (e.g. promethazine).
8. History of significant cardiac conduction block.
9. History of malignancy of any organ system (other than localized squamous or basal cell carcinoma of the skin or adequately treated cervical cancer), treated or untreated, within the past 3 years, regardless of whether there is evidence of local recurrence or metastases.
10. Estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2; AST, ALT, or alkaline phosphatase > 3 times the upper limit of normal.
11. Any ophthalmological disease which may prevent accurate infrared oculography assessment.
12. Suicidal ideation or behaviour in 6 months prior to baseline.
13. History of drug or alcohol abuse within the past year.
14. Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal or other major diseases that in the PI's judgement may affect interpretation of study results or patient safety.
15. History of or presence of clinically significant medical illness or laboratory abnormality that, in the opinion of the investigator would preclude participation in the study.
16. Pregnancy at the time of inclusion into the study or planning on breastfeeding within the first 7 months after inclusion in the study.
17. Involvement in other study protocol simultaneously without prior approval.
18. Insufficient proficiency in reading Dutch or English.
19. Unable or unwilling to suspend driving for a duration of 6 months.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The relative change in Versional Dysconjugacy Index (VDI) of Area under the Curve (AUC) from baseline will be compared between the treatment and control group at the end of treatment (6 months) and multiple follow-up periods (12, 24 and 36 months)

Investigational products

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

Test 2

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

MS Center Amsterdam

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

MS Center Amsterdam

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 18 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