Disease Modifying Therapies Withdrawal in Inactive Relapsing-Remitting Multiple Sclerosis Patients Aged 55 and Over: a Multicentric, Randomized, Controlled, Open-Label Clinical Trial - Twins

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Les Hopitaux Universitaires De Strasbourg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

3 Feb 2025 → ongoing

Decision date (initial)

2024-08-27

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Ministry of Health

External identifiers

EU CT number

2024-513475-41-00

ClinicalTrials.gov

NCT06663189

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To demonstrate the non-inferiority in disease activity-free survival between continuation and discontinuation of treatment in stable RRMS patients aged 55 and over. These results could lead to a modification of the standard care protocol to meet the needs of older populations.

Secondary objectives 9

1. To compare both groups (treatment discontinuation vs treatment continuation) in terms of: 1. Time to relapse
2. 2. Relapse rate
3. 3. Progression to secondary progressive multiple sclerosis forms
4. 4. Disability progression
5. 5. Cognitive impairment
6. 6. Quality of life
7. 7. Incidence of treatment-emergent adverse events , side effects (including infections)
8. 8. Comorbidities
9. 9. Medico-economic impact of treatment discontinuation

Conditions and MedDRA coding

Multiple Sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Patient (male or female) aged 55 and over
2. 2. RRMS (Relapsing-Remitting Multiple Sclerosis) diagnosis according to revised McDonald 2017 criteria
3. 3. First MS symptom > 5 years ago. If the date is unknown, RRMS diagnosis > 5 years ago
4. 4. Stable disease in the last 5 years according to the revised Lublin and Reingold classification 19 characterized by : a) Stable T2 lesions related to MS documented by brain MRI performed at least 5 years prior to inclusion versus MRI performed within 6 months prior to the inclusion visit, AND b) Non-worsened EDSS documented at least 5 years prior to inclusion versus EDSS documented within 6 months prior to inclusion visit, according to the investigator's judgment, AND c) The absence of relapses within 5 years prior to the inclusion visit
5. 5. Treated with a Moderate Efficacy Therapy (MET) for at least 5 consecutive years (IFN-β, glatiramer acetate, dimethyl fumarate, teriflunomide, diroximel fumarate) strictly used in accordance with their marketing authorization; switching from one first-line treatment to another is accepted if the reason for the change is related to personal convenience or intolerance to the first treatment.

Exclusion criteria 6

1. 1. Primary progressive or secondary progressive with or without relapse as defined by the revised Lublin and Reingold classification
2. 2. Previous or ongoing treatment with a High Efficacy therapy (HET), with the exception of induction therapy (mitoxantrone, stem cell transplantation, alemtuzumab) provided that the last administration took place at least 10 years prior to inclusion
3. 3. Contraindication to MRI (claustrophobia, weight ≥ 140 kg, pacemaker, cochlear implants, foreign body in eye, intracranial vascular clips, surgery in the 6 weeks prior to the beginning of the study, coronary stent implanted in the 8 weeks prior to the beginning of the study,…). NB: Gadolinium contraindication will not prevent recruitment of the patient; in this case MRI will be carried out without contrast product injection
4. 4. History of neurological disease affecting the central nervous system: hereditary degenerative CNS disease, degenerative cognitive disease, clinical or radiological history of a clinically significant cerebral arteriovenous malformation, or one that has bled, systemic autoimmune disease, sarcoidosis, Lyme disease…
5. 5. Chronic disease which requires chronic treatment with corticoids or immunosuppressors
6. 6. Uncontrolled cardiac, renal or hepatic disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first clinical and/or radiological disease activity during a period of 2 years.

Secondary endpoints 9

1. Secondary endpoints will be measured by comparing baseline scores/evaluations (M0) with the scores/evaluations at M6, M12, M18, and M24: 1. Kaplan Meier analysis of time to relapse
2. 2. Annual relapse rate (ARR)
3. 3. Transition to secondary progressive multiple sclerosis according to revised McDonald 2017 criteria
4. 4. Scores at EDSS, 25Foot/Walk, 9-HPT tests
5. 5. Scores at CSCT questionnaire
6. 6. Scores at SEP-59, EQ-5D, Hospital Anxiety and Depression (HAD) and Burden of Treatment (TBQ) Questionnaires
7. 7. Safety of treatments will be followed by the number and type of adverse or severe adverse events (AE/SAE) throughout the protocol ; Clinical examination, patient questioning; biological analysis in the case of suspected infection
8. 8. MS comorbidities questionnaire
9. 9. Average annual cost, incremental ratio cost/effectiveness and cost/utility ratios

Investigational products

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

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Les Hopitaux Universitaires De Strasbourg

Sponsor organisation

Les Hopitaux Universitaires De Strasbourg

Address

1 Avenue Moliere, Bp 49 Bp 49

City

Strasbourg Cedex 2

Postcode

67098

Country

France

Scientific contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Nicolas COLLONGUES

Public contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Nicolas COLLONGUES

Locations

1 EU/EEA country · 22 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 26 files

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

Application history

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