Anti-MAG IgM-associated Demyelinating PolyneuropathyPhase 2MAZINGANCT07392229
Zanubritnib and Anti-MAG Neuropathy
A Phase 2 study testing Zanubrutinib Oral Capsule in people with Anti-MAG IgM-associated Demyelinating Polyneuropathy, run by Azienda Ospedaliera di Padova at 7 sites in Italy.
Trial summary
The MAZINGA study is a multicenter, open-label, single-arm Phase IIA clinical trial designed to evaluate the efficacy, safety, and tolerability of zanubrutinib in patients with IgM anti-myelin-associated glycoprotein (anti-MAG) antibody-associated demyelinating polyneuropathy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anti-MAG IgM-associated Demyelinating Polyneuropathy
- What is being tested?
- Zanubrutinib Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 7 sitesItaly
- Study dates
- 24 Mar 2026to Mar 2031
- Phase
- Phase 2
- 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
- age ≥18 years;
- diagnosis of anti-MAG antibody polyneuropathy;
- neurophysiological (ENG/EMG) evidence of a demyelinating polyneuropathy with evidence of disproportionately prolonged distal motor latency in one or more nerves -excluding the median nerve if related to carpal tunnel syndrome
- IgM monoclonal protein underlying MGUS (based on the WHO definition of clonal lympho- plasmocytes <10%), Waldenstrom macroglobulinemia (based on the WHO definition of clonal lympho-plasmocytes ≥10%), marginal zone lymphoma, chronic lymphocytic leukemia or low- grade lymphoma not otherwise specified;
- presence of anti MAG antibodies (titer ≥ 7.000 BTU);
- neurophysiological (ENG/EMG) evidence of demyelinating polyneuropathy.
Who cannot join
- Previous treatment with BTK inhibitors
- Aggressive non-Hodgkin lymphoma or IgM multiple myeloma
- Evidence of moderate or severe motor nerve axonal damage, defined when occurring diffuse polyneuropathic denervation or a recruitment pattern lower than intermediate in ≥50% of muscles examined, and/or INCAT at lower limbs ≥4.
- ECOG >3
- Use of strong CYP3A inducers within 14 days prior to the first dose of zanubrutinib
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
Italy7 sites, 7 recruiting
- Recruiting
Neuroimmunology and neuromuscular disease unit, IRCCS Ospedale Clinico Humanitas di Rozzano, Milano
Milan, Milan, 20089
Pietro Emiliano Doneddu, MD, Medical Degree (Neurology), (+39) 0282247761, pietro.doneddu@hunimed.eu
- Recruiting
CTU Ematologia, Grande Ospedale Metropolitano Niguarda
Milan, Milan, 20162
Anna Maria Frustaci, MD, Medical Degree (Hematology), +390264442668, annamaria.frustaci@ospedaleniguarda.it
Lucia Bacigaluppi, +390264447597, lucia.bacigaluppi@ospedaleniguarda.it
- Recruiting
UOC Ematologia, Azienda Ospedale Università Padova
Padova, PD, 35128
Andrea Visentin, MD, Medical Degree (Hematology), +39 049 821 2298, andrea.visentin@aopd.veneto.it
Andrea Visentin, MD
- Recruiting
SC Ematologia 1 - Fondazione IRCCS Policlinico San Matteo
Pavia, PV, 27100
Martina La Fauci, +39 0382503084, cto-oh@smatteo.pv.it
Marzia Varettoni, MD
- Recruiting
UOSD Leucemia Linfatica Cronica, Fondazione Policlinico Universitario "A. Gemelli", IRCCS
Roma, RM, 00168
Florenzia Vuono, +39 0630157833, florenzia.vuono@policlinicogemelli.it
Luca Laurenti, MD
- Recruiting
SC Ematologia U, Ospedale Molinette, Torino (TO)
Torino, TO, 10126
Simone Ferrero, MD, Medical Degree (Hematology), +39 0116334220, simone.ferrero@unito.it
- Recruiting
SC UCO Ematologia, Ospedale Maggiore di Trieste
Trieste, Trieste, 34129
Francesco Zaja, Prof., Medical Degree (Hematology), +390403992015, francesco.zaja@asugi.sanita.fvg.it
Maria Chiara Rossetti, + 390403992897, mariachiara.rossetti@asugi.sanita.fvg.it
About this study
Official title: Zanubrutinib, a Second Generation BTK Inhibitor, in Anti-MAG Antibody Neuropathy: a Phase II Italian Multicenter Clinical Trial (MAZINGA)
The MAZINGA study is a multicenter, open-label, single-arm Phase IIA clinical trial designed to evaluate the efficacy, safety, and tolerability of zanubrutinib in patients with IgM anti-myelin-associated glycoprotein (anti-MAG) antibody-associated demyelinating polyneuropathy. Anti-MAG neuropathy is a rare immune-mediated disorder frequently associated with IgM monoclonal gammopathies, including monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia, and other indolent B-cell lymphoproliferative disorders.
The primary objective of the study is to determine whether 12 months of treatment with zanubrutinib leads to a clinically meaningful neurological improvement, defined as an improvement of at least one point in at least two validated neurological scales. These include reductions in the Overall Neuropathy Limitations Scale (ONLS), INCAT Disability Score, and INCAT Sensory Sum Score (ISS), along with increases in the Medical Research Council (MRC) sum score and the I-RODS functional score.
Read more
Secondary objectives include the evaluation of neurophysiological improvement assessed by nerve conduction studies (ENG/EMG), particularly changes in distal motor latency, terminal latency index, and sensory action potential amplitude at 12, 24, and 48 months. Additional secondary endpoints assess hematological efficacy through overall response rate (complete response, very good partial response, or partial response), event-free survival, time to neurological progression, and overall survival. The safety profile of zanubrutinib will be characterized by the incidence, type, and severity of adverse events, serious adverse events, and events of special interest.
Eligible participants are adults (≥18 years) with a confirmed diagnosis of anti-MAG IgM-associated demyelinating polyneuropathy, evidence of a relevant IgM monoclonal gammopathy, elevated anti-MAG antibody titers, and measurable neurological disability. Both treatment-naïve and relapsed/refractory patients are eligible. Key exclusion criteria include prior treatment with BTK inhibitors, aggressive lymphomas, significant axonal damage, uncontrolled comorbidities, active infections, pregnancy, or conditions that could interfere with study participation or safety evaluation.
The planned sample size is approximately 50 patients recruited from nine Italian centers. Statistical analyses will compare neurological outcomes with historical controls, estimate survival endpoints using Kaplan-Meier methods, and explore associations between clinical outcomes and molecular features. This study aims to provide robust prospective evidence on the role of BTK inhibition in anti-MAG neuropathy and to inform future therapeutic strategies for this rare and disabling condition.
- Being tested
- Zanubrutinib Oral Capsule
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zanubrutinib Oral CapsuleDrug
ZANUBRUTINIB ORAL CAPSULES or Brukinsa Oral Capsule
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Zanubrutinib Receives: Drug: Zanubrutinib Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients with neurological improvement defined as improvement of at least 1 point after 12 months of zanubrutinib treatment.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2026
- Study start24 Mar 2026
- Primary completionMar 2031 (estimated)
- Study completionMar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anti-MAG IgM-associated Demyelinating PolyneuropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliera di Padova
- Sponsor type
- University, hospital or other
- Collaborators
- ClinOpsHub Srl (CRO)
- Responsible party
- Principal investigator, Dr Andrea Visentin, Azienda Ospedaliera di Padova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07392229
- Sponsor's protocol ID
- MAZ-01
- Acronym
- MAZINGA
- Status last verified
- Aug 2026
- First submitted
- 21 Jan 2026
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zanubrutinib, a Second Generation BTK Inhibitor, in Anti-MAG Antibody Neuropathy: a Phase II Italian Multicenter Clinical Trial (MAZINGA)
- ClinicalTrials.gov ID
- NCT07392229
- Acronym / sponsor ID
- MAZINGA / MAZ-01
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Azienda Ospedaliera di PadovaUniversity, hospital or other
- Collaborators
- ClinOpsHub Srl (CRO)
- Study start
- 24 Mar 2026 (actual)
- Primary completion
- Mar 2031 (estimated)
- Study completion
- Mar 2031 (estimated)
- First posted
- 6 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The MAZINGA study is a multicenter, open-label, single-arm Phase IIA clinical trial designed to evaluate the efficacy, safety, and tolerability of zanubrutinib in patients with IgM anti-myelin-associated glycoprotein (anti-MAG) antibody-associated demyelinating polyneuropathy. Anti-MAG neuropathy is a rare immune-mediated disorder frequently associated with IgM monoclonal gammopathies, including monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia, and other indolent B-cell lymphoproliferative disorders.
The primary objective of the study is to determine whether 12 months of treatment with zanubrutinib leads to a clinically meaningful neurological improvement, defined as an improvement of at least one point in at least two validated neurological scales. These include reductions in the Overall Neuropathy Limitations Scale (ONLS), INCAT Disability Score, and INCAT Sensory Sum Score (ISS), along with increases in the Medical Research Council (MRC) sum score and the I-RODS functional score.
Secondary objectives include the evaluation of neurophysiological improvement assessed by nerve conduction studies (ENG/EMG), particularly changes in distal motor latency, terminal latency index, and sensory action potential amplitude at 12, 24, and 48 months. Additional secondary endpoints assess hematological efficacy through overall response rate (complete response, very good partial response, or partial response), event-free survival, time to neurological progression, and overall survival. The safety profile of zanubrutinib will be characterized by the incidence, type, and severity of adverse events, serious adverse events, and events of special interest.
Eligible participants are adults (≥18 years) with a confirmed diagnosis of anti-MAG IgM-associated demyelinating polyneuropathy, evidence of a relevant IgM monoclonal gammopathy, elevated anti-MAG antibody titers, and measurable neurological disability. Both treatment-naïve and relapsed/refractory patients are eligible. Key exclusion criteria include prior treatment with BTK inhibitors, aggressive lymphomas, significant axonal damage, uncontrolled comorbidities, active infections, pregnancy, or conditions that could interfere with study participation or safety evaluation.
The planned sample size is approximately 50 patients recruited from nine Italian centers. Statistical analyses will compare neurological outcomes with historical controls, estimate survival endpoints using Kaplan-Meier methods, and explore associations between clinical outcomes and molecular features. This study aims to provide robust prospective evidence on the role of BTK inhibition in anti-MAG neuropathy and to inform future therapeutic strategies for this rare and disabling condition.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Zanubrutinib Oral CapsuleZanubrutinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- age ≥18 years;
- diagnosis of anti-MAG antibody polyneuropathy;
- neurophysiological (ENG/EMG) evidence of a demyelinating polyneuropathy with evidence of disproportionately prolonged distal motor latency in one or more nerves -excluding the median nerve if related to carpal tunnel syndrome
- IgM monoclonal protein underlying MGUS (based on the WHO definition of clonal lympho- plasmocytes <10%), Waldenstrom macroglobulinemia (based on the WHO definition of clonal lympho-plasmocytes ≥10%), marginal zone lymphoma, chronic lymphocytic leukemia or low- grade lymphoma not otherwise specified;
- presence of anti MAG antibodies (titer ≥ 7.000 BTU);
Key exclusion criteria (5 listed)
- Previous treatment with BTK inhibitors
- Aggressive non-Hodgkin lymphoma or IgM multiple myeloma
- Evidence of moderate or severe motor nerve axonal damage, defined when occurring diffuse polyneuropathic denervation or a recruitment pattern lower than intermediate in ≥50% of muscles examined, and/or INCAT at lower limbs ≥4.
- ECOG >3
- Use of strong CYP3A inducers within 14 days prior to the first dose of zanubrutinib
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zanubrutinib Oral CapsuleZANUBRUTINIB ORAL CAPSULES or Brukinsa Oral Capsule | Drug | Treatment arm |
Primary outcome
The proportion of patients with neurological improvement defined as improvement of at least 1 point after 12 months of zanubrutinib treatment.
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zanubrutinib Oral Capsule in people with Anti-MAG IgM-associated Demyelinating Polyneuropathy, run by Azienda Ospedaliera di Padova at 7 sites in Italy.
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 6 inclusion and 5 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 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Andrea Visentin, Dr, Medical Doctor (+39 049 821 2298, ANDREA.VISENTIN@UNIPD.IT), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of patients with neurological improvement defined as improvement of at least 1 point after 12 months of zanubrutinib treatment. (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Nov 2026.