Rituximab therapy in anti-MAG patients with characteristics of good responders: THERAMAG study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Saint Etienne

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2024-10-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

DGOS

External identifiers

EU CT number

2024-516335-27-00

EudraCT number

2021-000009-25

ClinicalTrials.gov

NCT05136976

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Demonstrate the efficacy of rituximab versus placebo in a subgroup of anti-MAG patients presumed as good clinical responders to improve neurological disability assessed by I-RODS score between baseline and 12 months

Secondary objectives 4

1. Evaluate the efficacy of rituximab versus placebo in a subgroup of anti-MAG patients presumed as good clinical responders to improve neurological disability assessed by I-RODS score between baseline and 6 months
2. Evaluate the efficacy of rituximab versus placebo, between baseline, 6 months and 12 months, in a subgroup of anti-MAG patients presumed as good clinical responders to improve neurological disability assessed by: -Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, - Six minute walk test, - Timed 25-foot walk test, - 9 hole peg test, - ENMG motor sum score - ENMG sensory sum score - MUNIX sum score
3. Evaluate the tolerability and short-term safety of rituximab between baseline and 12 months
4. Explore the correlation between clinical response and change in anti-MAG antibody titre

Conditions and MedDRA coding

anti-MAG neuropathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Age over 18
2. Disease duration of 5 years or less and documented clinical worsening (clinical or ENMG or disability over the past 24 months)
3. IgM gammopathy, either MGUS or WM
4. Demyelinating polyneuropathy according to European Federation of Neurological Societies/Peripheral Nerve Society guidelines for chronic inflammatory demyelinating polyneuropathy on nerve conduction studies
5. Anti-MAG titre of 10 000 BTU or more
6. Total INCAT score of 1 point or more at baseline
7. Absence of immunoglobulin treatment within 3 months prior to inclusion
8. 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
9. Negative β-HCG in women of childbearing potential
10. Women of childbearing potential must agree to use contraception for 365 days following administration of rituximab

Exclusion criteria 19

1. Unable to give informed consent
2. History of severe allergic or anaphylactic reaction to chimeric monoclonal antibody
3. Hypersensitivity known to one of the compounds of polaramide or methylprednisolone
4. Previous treatment with rituximab
5. Diseases known to cause polyneuropathy (e.g. Disease known to cause neuropathy: type 1 diabetes or type 2 diabetes that is unbalanced or has been in progress for more than 5 years;, uncontrolled thyroid disease, vitamin B1 or B12 deficiency, renal (GFR < 60ml ml/min/1,73 m2- MDRD formula) or liver disorder, myeloma, amyloidosis, cryoglobulinemia)
6. Indication of specific immunosuppressive therapy for WM
7. 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
8. Congestive heart failure (NYHA III or IV)
9. Known active bacterial, viral, fungal mycobacterial infection
10. History or known presence of recurrent or chronic infection (e.g. viral hepatitis, HIV syphilis, tuberculosis)
11. - history of cancer/solid tumors less than 3 years old or not in remission, or history of hematological malignancies. Patients with a history of cancer with solid tumors cured or in remission for at least three years may be included. Patients with a history of basal cell carcinoma and squamous cell carcinoma in situ of the skin, carcinoma in situ of the cervix, which have been removed and resolved, with healthy margins documented on pathology, may be included.
12. History of alcohol (more than two drinks a day for a woman, more than 4 glasses a day for a man [WHO definition]) or other drug abuse within 6 months prior to randomization
13. History or currently active primary or secondary immunodeficiency
14. White blood cell count < 1500/mm3 or platelet count < 75 000/mm3
15. Angle closure glaucoma
16. Urinary retention related to urethroprostatic disorders
17. Uncontrolled psychotic disorders
18. Severe liver failure
19. Recent vaccination with live vaccines (<3months) and vaccination with live virus vaccines is not recommended during the overall study period

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 9

1. INCAT disability score
2. 6 minutes walk test
3. Timed 25 foot walk test
4. 9 hole peg test
5. ENMG motor sum score
6. ENMG sensory sum score
7. MUNIX sum score
8. Adverse events
9. Anti-MAG titre

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Saint Etienne

Sponsor organisation

Centre Hospitalier Universitaire De Saint Etienne

Address

25 Boulevard Pasteur

City

Saint-Etienne

Postcode

42100

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Saint Etienne

Contact name

project manager

Public contact point

Organisation

Centre Hospitalier Universitaire De Saint Etienne

Contact name

project manager

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Results and documents

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

Documents 8 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