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Anti-MAG NeuropathyPhase 3THERAMAGNCT05136976

Rituximab Therapy in Anti-Myelin Associated Glycoprotein Patients With Characteristics of Good Responders

A Phase 3 study testing Rituximab infusion and Premedications in people with Anti-MAG Neuropathy, run by Centre Hospitalier Universitaire de Saint Etienne at 15 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Anti-MAG neuropathy is a progressively disabling orphan rare disorder due to a monoclonal immunoglobulin M(IgM) gammopathy displaying reactivity toward MAG, a glycoprotein of the peripheral nervous system. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Anti-MAG Neuropathy
What is being tested?
Rituximab infusion and Premedications
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
90 participants
Where
15 sitesFrance
Study dates
29 Jun 2023to Dec 2028
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Disease duration of 5 years or less and documented clinical worsening (clinical or ENMG or disability) over the past 24 months
  • IgM gammopathy, either MGUS or Waldenstrom Macroglobulinemia (WM)
  • Demyelinating polyneuropathy according to European Federation of Neurological Societies/Peripheral Nerve Society guidelines for chronic inflammatory demyelinating polyneuropathy on nerve conduction studies.
  • Anti-MAG titre of 10 000 BTU or more
  • Total INCAT score of 1 point or more at baseline
  • Absence of immunoglobulin treatment within 3 months prior to inclusion.
Show all 9Show fewer
  • Absence of immunosuppressive therapy within 6 months prior to inclusion, including steroid therapy of 2 months or more as part of the management of neuropathy.
  • Negative β-human chorionic gonadotropin (HCG) in women of childbearing potential
  • Women of childbearing potential must agree to use contraception for 365 days following administration of rituximab.

Who cannot join

  • - Unable to give informed consent
  • History of severe allergic or anaphylactic reaction to chimeric monoclonal antibody
  • Hypersensitivity known to one of the compounds of polaramine or methylprednisolone
  • Previous treatment with rituximab
  • Diseases known to cause polyneuropathy (e.g. diabetes, uncontrolled thyroid disease, vitamin B1 or B12 deficiency, renal (GFR < 60ml ml/min/1,73 m2- Modification of Diet in Renal Disease (MDRD) formula) or liver disorder, myeloma, amyloidosis, cryoglobulinemia)
  • Indication of specific immunosuppressive therapy for WM
Show all 19Show fewer
  • Significant uncontrolled disease at baseline such as cardiovascular (including cardiac arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine or gastrointestinal or any other significant disease that may prevent patient from participating in the study
  • Congestive heart failure (NYHA III or IV)
  • Known active bacterial, viral, fungal mycobacterial infection
  • History or known presence of recurrent or chronic infection (e.g. viral hepatitis, HIV syphilis, tuberculosis).
  • History of cancer, including solid tumors and haematological malignancies (except basal cell and in situ squamous carcinoma of the skin, in situ carcinoma of the cervix of the uterus that have been excised and resolved, with documented clear margins on pathology)
  • History of alcohol (more than two drinks a day for a woman, more than 4 glasses a day for a man [World Health Organization (WHO) definition]) or other drug abuse within 6 months prior to randomization
  • History or currently active primary or secondary immunodeficiency
  • White blood cell count < 1500/mm3 or platelet count < 75 000/mm3
  • Angle closure glaucoma,
  • Urinary retention related to urethroprostatic disorders,
  • Uncontrolled psychotic disorders,
  • Severe liver failure,
  • Recent vaccination with live vaccines (<3months) and vaccination with live virus vaccines is not recommended during the overall study period.

Trial locations and contacts

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

Anne-Laure KAMINSKY, MD contact

(0)4 77 82 95 10 ext. +33

a.laure.kaminsky@chu-st-etienne.fr

Carine LABRUYERE, CRA contact

(0)4 77 12 04 69 ext. +33

carine.labruyere@chu-st-etienne.fr

15 sites in 1 country

France15 sites, 15 recruiting

  • CHU Brest - La cavale blanche

    Brest, 29200

    Jean-Baptiste NOURY, MD

    Recruiting

  • CHU Grenoble - La tronche

    Grenoble, 38700

    Martial MALLARET, MD

    Recruiting

  • CHU Lille - Roger Salengro

    Lille, 59037

    Céline TARD, MD

    Recruiting

  • CHU Limoges - Dupuytren

    Limoges, 87170

    Laurent MAGY, PhD

    Recruiting

  • HCL lyon

    Lyon, 69002

    Juliette SVAHN

    Recruiting

  • CHU La Timone - APHM

    Marseille, 13915

    Shahram Attarian, PhD

    Recruiting

  • CHU Nancy- Hôpital central

    Nancy, 54035

    Maud MICHAUD, MD

    Recruiting

  • Hôtel-Dieu et Hôpital GR Laënnec - CHU Nantes

    Nantes

    Yann Dr PEREON, +33 240 083 704, Yann.Pereon@univ-nantes.fr

    Recruiting

  • CHU Nice - Pasteur

    Nice, 06031

    Sabrina SACCONI, MD

    Recruiting

  • APHP Pitié Salpêtrière

    Paris, 75651

    Thierry MAISONOBE, MD

    Recruiting

  • APHP - Kremlin-Bicêtre

    Paris, 94270

    Andoni ECHANIZ-LAGUNA, PhD

    Recruiting

  • CHU de Saint-Etienne

    Saint-Etienne

    Anne-Laure KAMINSKY, MD

    Recruiting

  • CHU Strasbourg - Hautepierre

    Strasbourg, 67091

    Jean-Baptiste CHANSON, MD

    Recruiting

  • CHU Toulouse - Pierre-Paul Riquet

    Toulouse, 31059

    Pascal CINTAS, MD

    Recruiting

  • CHU Tours - Bretonneau

    Tours, 37044

    Philippe CORCIA, PhD

    Recruiting

Other trials in France

About this study

Official title: Rituximab Therapy in Anti-Myelin Associated Glycoprotein Patients With Characteristics of Good Responders:

Anti-MAG neuropathy is a progressively disabling orphan rare disorder due to a monoclonal immunoglobulin M(IgM) gammopathy displaying reactivity toward MAG, a glycoprotein of the peripheral nervous system. Its prevalence is around 1/100000 and to date, no treatment has proven efficacy in this disease, including rituximab in 2 Randomized Controlled Trails(RCTs).

Read the detailed description

However these trials have included unselected anti-MAG patients and methodological issues have been raised.

In COFRAMAG study, the largest cohort worldwide of anti-MAG patients, predictors of clinical response to rituximab were identified through analysis of 92 treated patients: shorter disease duration and anti-MAG titre above 10000 BTU. Thus this study will focus on rituximab efficacy in a subset of patients with disease duration of less than 2 years and anti-MAG titre above 10000 Buhlmann Titer Units (BTU). The investigators selected Inflammatory Rasch-built Overall Disability Scale (I-RODS) as primary outcome measure because its responsiveness was proven higher than INCAT/ Overall Neuropathy Limitation Score (ONLS) scales to detect clinical meaningful changes in newly treated patients with inflammatory neuropathies.

Being tested
Rituximab infusion, Placebo infusion, Premedications
Keywords
Neuropathy, Anti-MAG, Rituximab, I-RODS, placebo

What participants receive

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

  • Rituximab infusionDrug

    Also called Mabthera

    2 infusions of 1 gram of rituximab at a 2 week interval (day 1 followed by day 15).

  • Placebo infusionDrug

    Also called Sodium chloride (NaCl)

    2 infusions of placebo at a 2 week interval.

  • PremedicationsDrug

    Premedications prior to rituximab or placebo infusions:

    • IV Dexchlorpheniramine Maleate IV: 10 mg
    • IV Methylprednisolone: 40 mg
    • PO Paracetamol : 1 gram
Study groups in NCT05136976
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPatient with anti-MAG neuropathy will be included. They will randomized in placebo or Rituximab group. They will have the same premedications prior to rituximab or placebo infusions: * IV Dexchlorpheniramine Maleate IV: 10 mg * IV Methylprednisolone: 40 mg * PO Paracetamol : 1 gram
Receives: Drug: Placebo infusion; Drug: Premedications
RituximabActive comparatorPatient with anti-MAG neuropathy will be included. They will randomized in placebo or Rituximab group. They will have the same premedications prior to rituximab or placebo infusions: * IV Dexchlorpheniramine Maleate IV: 10 mg * IV Methylprednisolone: 40 mg * PO Paracetamol : 1 gram
Receives: Drug: Rituximab infusion; Drug: Premedications

What is being measured

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

  1. I-RODS score

    Clinical response defined as a 4 points (or more) change of I-RODS between baseline and 12 months.

    I-RODS is a 24-item patient-reported outcome measure which maximum score is 48. It is a linearly weighted scale that specifically captures activity and social participation limitations in patients with inflammatory neuropathies, including Monoclonal Gammopathy of Unknown Significance (MGUS) related polyneuropathies.

    Measured: Baseline and 12 months

Secondary outcomes (9)

  1. Inflammatory Neuropathy Cause and Treatment (INCAT) disability score

    The INCAT (Inflammatory Neuropathy Cause and Treatment) disability score is a measure of activity limitation with minimum score at 0 and maximum at 10.

    Measured: Months: 0, 6, 12

  2. Six minute walk test

    Six minute walk test will be realized.

    Measured: Months : 0, 6, 12

  3. Timed 25- foot walk (FW) test

    The T25-FW is a quantitative test of mobility and performance of leg function based on a timed outward journey of 25 steps, and a timed return journey of 25 steps. The score for the T25-FW is the average of the two completed trials

    Measured: Months : 0, 6, 12

  4. 9 hole peg test

    The nine hole peg test is a standardized, quantitative assessment used to measure finger dexterity. Scores are based on the time taken to complete the test activity, recorded in seconds

    Measured: Months : 0, 6, 12

  5. ElectroNeuroMyography (ENMG)

    An ENMG will be realized.

    Measured: Months : 0, 6, 12

  6. ENMG sensory sum score

    ENMG sensory sum score will be realized.

    Measured: Months : 0, 6, 12

  7. Score Motor unit number index (MUNIX)

    Score MUNIX will be realised.

    Measured: Months : 0, 6, 12

  8. Incidence of Treatment-Emergent Adverse Events of Rituximab

    Consideration of adverse effects of Rituximab

    Measured: Months : 0, 6, 12

  9. the anti-MAG antibody titre.

    To study the correlation between the clinical response and the evolution of the anti-MAG antibody titre.

    Measured: Months : 0, 6, 12

Timeline

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

  1. First posted30 Nov 2021
  2. Study start29 Jun 2023
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2028 (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
Model description
The THERAMAG study is a French academic multicentre, randomized, double-blind trial sponsored by the University Hospital of Saint-Etienne, comparing rituximab infusion to placebo infusion in anti-MAG patients presumed as good clinical responders.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05136976
Sponsor's protocol ID
19PH226
Other IDs
2021-000009-25
Acronym
THERAMAG
Status last verified
Nov 2025
First submitted
16 Nov 2021
Last updated
24 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rituximab infusion and Premedications in people with Anti-MAG Neuropathy, run by Centre Hospitalier Universitaire de Saint Etienne at 15 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 19 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: looking for participants now, as of the sponsor's last update on 24 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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. Some participants in this study may receive a placebo. 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 Anne-Laure KAMINSKY, MD ((0)4 77 82 95 10 ext. +33, a.laure.kaminsky@chu-st-etienne.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

I-RODS score (time frame: Baseline and 12 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 NCT05136976.

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 24 Nov 2025.

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