Zanubritnib and anti-MAG neuropathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliera di Padova

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

24 Mar 2026 → ongoing

Decision date (initial)

2025-12-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2025-523091-23-00

ClinicalTrials.gov

NCT07392229

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To investigate whether 12 months zanubrutinib treatment lead to an improvement of at least 1 point in
at least 2 neurological scales, such as Overall Neuropathy Limitations Scale (ONLS), INCAT disability,
INCAT sensory sum scores (ISS), MRC sum score, I-RODS functional score.

Secondary objectives 1

1. ● To evaluate ENG/EMG improvement, in particular a reduction of distal motor latency, or an increase of terminal latency index or an increase of sensory nerve action potential amplitude (see criteria of evaluation) after zanubrutinib treatment at 12, 24 and 48 months; ● To evaluate the efficacy by hematological overall response rates, event free survival, time to progression (defined as worse of at least 1 point in two neurological scales), overall survival; ● To study the safety profile of zanubrutinib in patients with anti–MAG antibody polyneuropathy. Exploratory objectives ● To evaluate the quality of life or patients by FACT-GOG-NTX-13 QOL questionnaire; ● To identify any correlation between neurologic response (assessed by the neurological scaled mentioned in the primary endpoint) and hematologic overall response (CR, VGPR, PR) at 24 and 48 months, event free survival, time to progression and overall survival with demographic, clinical and molecular features of the patients at baseline; ● To evaluate the reduction of MYD88 mutational burden by cf-DNA during treatment; To evaluate the emergence of BTK and PLCG2 mutational status in relapsing patients.

Conditions and MedDRA coding

Peripheral anti-MAG neuropathy, waldenstrom macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia, monoclonal gammopathy of unknown significance

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. ● Age ≥18 years; ● diagnosis of anti-MAG antibody polyneuropathy; ● diagnosis of anti-MAG antibody polyneuropathy; ● IgM monoclonal protein underlying MGUS, 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)

Exclusion criteria 1

1. ● Previous treatment with BTK inhibitors ● Aggressive non-Hodgkin lymphoma or IgM multiple myeloma ● Evidence of moderate or severe motor nerve axonal damage ● ECOG >3 ● Requiring ongoing therapy with strong or moderate cytochrome P450 3A (CYP3A) inducer. Use of strong/moderate CYP3A inducers within 14 days prior to the first dose of zanubrutinib (see Drug-interaction section). ● creatinine clearance <30mL/min

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients with neurological improvement defined as improvement of at least 1 point in at least 2 neurological scales (ONLS, INCAT disability, INCAT sensory sum scores (ISS), MRC sum score, I-RODS functional score) at 12 months of zanubrutinib treatment.

Secondary endpoints 1

1. ● The proportion of patients with neurological improvement after 24 and 48 months of zanubrutinib; ● the proportion of patients with ENG/EMG improvement since the baseline, assessing decrease of distal motor latency, increase of terminal latency index, increase of sensory nerve action potential amplitude (see criteria of evaluation) at upper limbs after zanubrutinib treatment at 12, 24 and 48 months; ● levels of monoclonal protein, IgM and of anti-MAG antibody titers at 12, 24 and 48 months.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliera di Padova

Sponsor organisation

Azienda Ospedaliera di Padova

Address

Via Nicolo' Giustiniani 2

City

Padova

Postcode

35128

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliera di Padova

Contact name

Principal Investigator

Public contact point

Organisation

Azienda Ospedaliera di Padova

Contact name

Principal Investigator

Locations

1 EU/EEA country · 9 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 19 files

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

Application history

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