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Relapsing-remitting Multiple Sclerosis (RRMS)Phase 3TWINSNCT06663189

Disease Modifying Therapies Withdrawal in Inactive Relapsing-remitting Multiple Sclerosis Patients Aged 55 and Over (TWINS : Therapies Withdrawal IN Relapsing Multiple Sclerosis)

A Phase 3 study testing treatment withdrawal, Usual DMT continuation and MRI in people with Relapsing-remitting Multiple Sclerosis (RRMS), run by University Hospital, Strasbourg, France at 22 sites in France.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by loss of motor and sensory function, that results from immune-mediated inflammation, demyelination and subsequent axonal damage. Read more about this study

Who is it for?
Ages 55 years and older
What is being tested?
treatment withdrawal, Usual DMT continuation and MRI
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
22 sitesFrance
Study dates
Jan 2025to Jun 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient (male or female) aged 55 and over
  • RRMS diagnosis according to revised McDonald 2017 criteria
  • First MS symptom >5 years ago. If the date is unknown, RRMS diagnosis >5 years ago
  • Stable disease in the last 5 years according to the revised Lublin and Reingold classification characterized by :
  • Stable T2 lesions documented by MRI performed at least 5 years prior to inclusion versus MRI performed within 6 months prior to the inclusion visit, AND Stable 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 The absence of relapses within 5 years prior to the inclusion visit
  • Treated with a Moderate Efficacy Therapy (MET) for at least 5 consecutive years (IFN-β, glatiramer acetate, dimethyl fumarate, teriflunomide, diroximel fumarate); 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.
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  • Patient with affiliation to a social security regimen
  • Patient able to understand the objectives and risks associated with the research and to give informed consent to the study
  • Patient willing and able to comply with study procedures for the duration of the study

Who cannot join

  • Primary progressive or secondary progressive with or without relapse as defined by the revised Lublin and Reingold classification
  • 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.
  • 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
  • History of neurological disease affecting the central nervous system: hereditary degenerative CNS disease, degenerative cognitive disease, systemic autoimmune disease, sarcoidosis, Lyme disease…
  • Chronic disease which requires chronic treatment with corticoids or immunosuppressors
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  • Uncontrolled cardiac, renal or hepatic disease
  • Patient participating in another interventional trial (drug or a medical device) or patient who are still within an exclusion period
  • Patient wishing to discontinue background therapy, whether or not they are experiencing adverse effects.
  • Patient not considering discontinuing background therapy, whether or not they are experiencing adverse effects.
  • Pregnant or breastfeeding woman
  • Patient with difficulty to read or understand French,
  • Patient subject to a legal protection measure

Trial locations and contacts

22 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Sarah HUSTACHE contact

03 3 88 11 54 15 ext. 00 33

dpidrci@chru-strasbourg.fr

22 sites in 1 country

France22 sites

  • CHU de Bordeaux-Hôpital Pellegrin

    Bordeaux, 33076

    Aurélie RUET, MD, 05 56 79 55 21 ext. +33 (0), aurelie.ruet@chu-bordeaux.fr

    Aurélie RUET, MD

  • CHU de Caen-Hôpital Côte de Nacre

    Caen, 14033

    Pierre BRANGER, (0) 2 31 06 46 17 ext. 00 33, branger-p@chu-caen.fr

    Pierre BRANGER

  • CHU de Clermont-Ferrand-Hôpital Gabriel Montpied

    Clermont-Ferrand, 63003

    Pierre CLAVELOU, (0)4 73 75 07 50 ext. 00 33, pclavelou@chu-clermontferrand.fr

    Pierre CLAVELOU

  • Assistance Publique des Hôpitaux de Paris (APHP)-Hôpital Henri Mondor

    Créteil, 94010

    Alain CREANGE, MD PhD, 01 49 81 23 15 ext. +33 (0), alain.creange@aphp.fr

    Alain CREANGE, MD PhD

  • CHU de Dijon-Hôpital du Bocage

    Dijon, 21079

    Thibault MOREAU, (0)3 80 29 55 84 ext. 00 33, thibault.moreau@chu-dijon.fr

    Thibault MOREAU

  • CH de Gonesse

    Gonesse, 95500

    Eric MANCHON, (0)1 34 53 21 21 ext. 00 33, eric.manchon@ch-gonesse.fr

    Eric MANCHON

  • CHU de Grenoble Alpes

    La Tronche, 38700

    Catalina COCLITU, MD, 04 76 76 58 71 ext. +33 (0), cicoclitu@chu-grenoble.fr

    Catalina COCLITU, MD

  • Groupement des Hôpitaux de l'Institut Catholique de Lille Hôpital Saint Vincent de Paul

    Lille, 59020

    Arnaud KWIATKOWSKI, MD, 03 20 87 49 01 ext. +33 (0), kwiatkowski.arnaud@ghicl.net

    Arnaud KWIATKOWSKI, MD

  • CHU de Lille-Hôpital Roger Salengro

    Lille, 59037

    Hélène ZEPHIR THI, (0)3 20 44 68 46 ext. 33, h-zephir@chru-lille.fr

    Hélène ZEPHIR THI

  • CHU de Limoges-Hôpital Dupuytren

    Limoges, 87042

    Maxime MERINDOL, (0)5 55 05 65 68 ext. 00 33, maxime.merindol@chu-limoges.fr

    Maxime MERINDOL

  • Assistance Publique des Hôpitaux de Marseille (APHM)-Hôpital La Timone Adultes

    Marseille, 13005

    Bertrand AUDOIN, (0)4 91 38 59 34 ext. 00 33, bertrand.AUDOIN@ap-hm.fr

    Bertrand AUDOIN

  • CHU de Montpellier-Hôpital G. De Chauliac

    Montpellier, 34295

    Xavier AYRIGNAC, (0)467337413 ext. 00 33, x-ayrignac@chu-montpellier.fr

    Xavier AYRIGNAC

  • CHU de Nancy -Hôpital Central

    Nancy, 54035

    Guillaume MATHEY, MD, 03 83 85 16 88 ext. +33 (0), G.MATHEY@chru-nancy.fr

    Guillaume MATHEY, MD

  • CHU de Nice-Hôpital Pasteur

    Nice, 06002

    Mikaël COHEN, 04 92 03 79 01 ext. 00 33, Cohen.m@chu-nice.fr

    Mikaël COHEN

  • CHU de Nîmes

    Nîmes, 30029

    Eric THOUVENOT, MD PhD, 04 66 68 32 61 ext. +33 (0), eric.thouvenot@chu-nimes.fr

    Eric THOUVENOT, MD PhD

  • Assistance Publique des Hôpitaux de Paris (APHP)-Hôpital Pitié-Salpêtrière

    Paris, 75013

    Elisabeth MAILLART, 01 42 17 62 05 ext. 00 33, elisabeth.maillart@ahp.fr

    Elisabeth MAILLART

  • Fondation Ophtalmologique Rothschild

    Paris, 75019

    Caroline BENSA, (0)1 48 03 68 52 ext. 00 33, cbensa@for.paris

    Caroline BENSA

  • CHU de Rennes-C.H.R. Pontchaillou

    Rennes, 35033

    Laure MICHEL, (0)299284266 ext. 00 33, laure.michel@chu-rennes.fr

    Laure MICHEL

  • CHU de Rouen-Hôpital Charles Nicolle

    Rouen, 76038

    Bertrand BOURRE, (0)2 32 88 58 11 ext. 00 33, bertrand.bourre@chu-rouen.fr

    Bertrand BOURRE

  • CHU Nantes -CIC de Neurologie

    Saint-Herblain, 44 093

    David-Axel LAPLAUD, (0)2 40 16 52 12 ext. 00 33, david.laplaud@chu-nantes.fr

    David-Axel LAPLAUD

  • Les Hôpitaux Universitaires de Strasbourg

    Strasbourg, 67000

    Laura DROCTOVE, laura.droctove@chru-strasbourg.fr

    Nicolas COLLONGUES, MD, PhD

  • CHU de Tours

    Tours, 37044

    Ines DOGHRI, MD, 02 47 47 37 22 ext. +33 (0), I.DOGHRI@chu-tours.fr

    Ines DOGHRI, MD

Other trials in France

About this study

Official title: Disease Modifying Therapies Withdrawal in Inactive Relapsing-remitting Multiple Sclerosis Patients Aged 55 and Over: A Multicentric, Randomized, Controlled, Open-label Clinical Trial (TWINS : Therapies Withdrawal IN Relapsing Multiple Sclerosis)

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by loss of motor and sensory function, that results from immune-mediated inflammation, demyelination and subsequent axonal damage. It is the most common cause of neurological disability in young adults, involving a long-term therapeutic follow-up. 85% of the patients are diagnosed with Relapsing-Remitting form of MS (RRMS). This form is characterized by clearly defined acute or subacute neurological symptoms (relapses) followed by periods of partial to complete recovery.

Disease-modifying therapies (DMT) used to treat RRMS are immunomodulatory or suppressor molecules which have proven efficacy in limiting disease activity (decreasing relapse rate and delaying time to disease progression).

Read more

However, the long-term safety of DMT is uncertain, as there is an increased risk of developing adverse events or infections (sometimes severe) such as observed in the last pandemic of COVID-19 (higher risk of infection), highlighting the need to reassess the benefit/risk ratio of maintaining immunomodulatory or suppressive therapy in the MS population. In elderly patients with comorbidity, this risk is further increased. To date, few studies on the discontinuation of treatment in elderly RRMS patients have been conducted. However, those available demonstrate that there was no difference in relapse rates between patients who continued or discontinued treatment. These results are consistent with immunosenescence studies in RRMS that suggested a negative correlation between relapse rate/inflammatory processes and age. On the contrary, there is evidence indicating a positive correlation between age and the number of infections.

In addition, in the current context in France, it is important to take into account the medico-social cost associated with long-term treatments. In France, the average estimated annual cost per patient is 12,000€, more than half of which is attributed to medications.Furthermore, with age progression, an inversion of the benefit/cost assessment has been observed in treated patients.

Considering these medical and medico-social factors, it is reasonable to question the value of continuing treatment in stable patients with RRMS over 55 years.

This is a randomized, controlled, multicentric, open-label, parallel groups, 1:1 ratio non-inferiority clinical trial, comparing (1) a group that will stop treatment, to (2) a group that will continue treatment, over the course of 2 years, to determine the survival rate without MS activity defined clinically or by imaging.

The patients in both arms will be followed over 2 years after randomization. 5 visits will be performed for all patients: inclusion/randomization visit (M0) and 4 follow-up visits every 6 months (M6, M12, M18, and M24). An additional phone call at M3 is planned.

Being tested
treatment withdrawal, Usual DMT continuation, MRI, Quality of Life questionnaires, Disability evaluation tests
Medical subject headings
Multiple Sclerosis, Relapsing-Remitting

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • treatment withdrawalDrug

    Patients will STOP their DMT

  • Usual DMT continuationDrug

    Patients will continue their DMT during the trial as usual : Interferon-β (IFN-β), glatiramer acetate, dimethyl fumarate, teriflunomide or diroximel fumarate

  • MRIOther

    Cerebral+spinal cord enhanced MRI (M0) Cerebral enhanced MRI (M6, Relapse early visit) Unenhanced cerebral MRI (M12, M18, M24, Relapse distant visit

  • Quality of Life questionnairesBehavioural

    EQ-5D5L: EuroQol-5-Dimension 5 levels Burden of Treatment Questionnaire (BTQ self-administered questionnaires) Hospital Anxiety and Depression (HAD) questionnaire

  • Disability evaluation testsOther

    EDSS: Expanded Disability Status Scale 25Foot/Walk 9-HPT:Nine Hole Peg Test

Study groups in NCT06663189
Study groupRoleWhat they receive
ExperimentalExperimentalTreatment withdrawal; patients will stop their Disease Modifying Treatment (DMT)
Receives: Drug: treatment withdrawal; Other: MRI; Behavioral: Quality of Life questionnaires; Other: Disability evaluation tests
Control armActive comparatorPatients will continue their DMT as per routine pratice
Receives: Drug: Usual DMT continuation; Other: MRI; Behavioral: Quality of Life questionnaires; Other: Disability evaluation tests

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    A clinical activity (relapse) is defined by the occurrence of new or worsening of neurological symptoms linked to MS. Relapses must meet the following criteria:

    • Symptoms must last at least 24 hours, without other clinical factors leading to confusion (fever, infection, lesion, drug adverse events)
    • Must be followed by improvement or resolution of the neurological state within 30 days
    • New symptoms or worsening of neurological state must be accompanied by an objective neurologic state aggravation
    • The neurological symptom must be linked to the modified FSS (pyramidal, cerebellar, brainstem, sphincter, mental, sensory or visual functions)

    A radiological activity is defined if MRI shows either:

    • at least 3 new or enlarged T2 ≥ 3 mm on the same exam or
    • at least 3 cumulative new or enlarged T2 lesions ≥ 3 mm during follow up or
    • one enhanced gadolinium lesion compared to the previous MRI.

    Measured: From enrollment to the end of study visit at 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2024
  2. Study startJan 2025 (estimated)
  3. Primary completionJan 2027 (estimated)
  4. Study completionJun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06663189
Sponsor's protocol ID
8670
Other IDs
2024-513475-41-00
Acronym
TWINS
Status last verified
Jan 2025
First submitted
22 Oct 2024
Last updated
3 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing treatment withdrawal, Usual DMT continuation and MRI in people with Relapsing-remitting Multiple Sclerosis (RRMS), run by University Hospital, Strasbourg, France at 22 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 3 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sarah HUSTACHE (03 3 88 11 54 15 ext. 00 33, dpidrci@chru-strasbourg.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to first clinical and/or radiological disease activity during a period of 2 years. (time frame: From enrollment to the end of study visit at 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06663189.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2025.

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