RecruitingRare disease

A Study of Zanubrutinib for Patients with Anti-MAG Antibody Neuropathy Associated with Blood Disorders or Abnormal Protein in the Blood

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study involves patients with a nerve condition called peripheral anti-MAG neuropathy, which is a type of nerve damage that affects the arms and legs. This condition occurs when the body produces abnormal antibodies called anti-MAG antibodies that attack the protective coating around nerves. Patients in this study also have an underlying blood condition, which may be Waldenstrom macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia, or monoclonal gammopathy of unknown significance. These are conditions where certain white blood cells grow abnormally and produce abnormal proteins in the blood. The treatment being tested is zanubrutinib, also known by its code name BGB-3111, which is taken as a capsule by mouth. This medication works by blocking a specific protein in cells that helps the abnormal blood cells survive and produce the harmful antibodies.

The purpose of the study is to find out whether treatment with zanubrutinib for twelve months can lead to improvement in nerve function as measured by various scales that assess strength, sensation, and ability to perform daily activities. These scales help doctors understand how well patients can move, feel sensations, and carry out everyday tasks. The study will measure whether patients improve by at least one point on at least two of these measurement scales after one year of treatment.

During the study, patients will take zanubrutinib capsules daily for up to forty-eight months. The maximum daily amount is three hundred twenty milligrams, and the maximum total amount in a day is four hundred eighty milligrams. Doctors will regularly check nerve function using the measurement scales and will also perform nerve conduction studies, which are tests that measure how well electrical signals travel through the nerves. Blood tests will be done to measure the levels of abnormal proteins and anti-MAG antibodies at twelve, twenty-four, and forty-eight months to see if the treatment is reducing these harmful substances in the blood.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Treatment period with zanubrutinib
Upon joining the study, you will begin treatment with zanubrutinib, a medication taken by mouth in capsule form.
The treatment will continue for 12 months. Zanubrutinib is a type of medicine that blocks a specific protein called BTK, which is involved in the disease process affecting your nerves.
During this period, your condition will be monitored using several assessment scales that measure your nerve function, sensation, muscle strength, and ability to perform daily activities.
Step 2
Assessment at 12 months
After completing 12 months of treatment, your neurological condition will be evaluated using five different scales.
These scales assess various aspects including limitations in daily activities, disability level, sensory function, muscle strength, and ability to perform specific tasks.
Tests will also be performed to measure the electrical activity of your nerves, checking for improvements in nerve signal transmission.
Blood tests will be conducted to measure the levels of certain proteins and antibodies in your blood, including the anti-MAG antibodies that are associated with your nerve condition.
Step 3
Continued treatment and assessment at 24 months
You will continue taking zanubrutinib for an additional 12 months, bringing the total treatment duration to 24 months.
At the 24-month point, the same neurological assessments will be repeated to evaluate any further changes in your condition.
Nerve conduction studies will be performed again to assess the electrical function of your nerves.
Blood tests will be repeated to monitor protein and antibody levels.
Step 4
Extended treatment and final assessment at 48 months
Treatment with zanubrutinib will continue for a total of 48 months, which is 4 years.
At the 48-month point, a comprehensive final evaluation will be conducted using the same neurological scales used at previous assessments.
Final nerve conduction studies will be performed to measure any long-term changes in nerve function.
Final blood tests will be conducted to assess the levels of monoclonal protein, IgM (a type of antibody), and anti-MAG antibody levels.

Who can join the trial?

4 criteria

You must be 18 years of age or older
You must have a diagnosis of anti-MAG antibody polyneuropathy, which is a condition where your immune system produces certain antibodies that damage the protective covering of your nerves, causing numbness, tingling, and weakness
You must have a monoclonal protein (an abnormal protein in your blood) of the IgM type caused by one of the following conditions: MGUS (a condition where abnormal proteins are present but not causing major problems), Waldenstrom macroglobulinemia (a rare type of slow-growing blood cancer), marginal zone lymphoma (a slow-growing cancer of white blood cells), chronic lymphocytic leukemia (a slow-growing cancer of blood and bone marrow), or another type of low-grade lymphoma (slow-growing cancer of the lymphatic system)
You must have anti-MAG antibodies in your blood with a level of at least 7,000 BTU, which is a measurement showing that these specific antibodies are present in sufficient amounts

Who cannot join the trial?

8 criteria

The study has not provided specific exclusion criteria in the available information
If you have any medical conditions or take medications, your doctor will need to review whether this study is appropriate for you
Women who are pregnant or breastfeeding may not be eligible, as is common in most clinical trials
People with serious heart, liver, or kidney problems may not be able to participate
Those taking certain medications that could interact with zanubrutinib (the study drug being tested) may be excluded
People with active infections or weakened immune systems may not qualify
Those who have participated in another clinical trial recently may need to wait before joining this study
People with known allergies to the study medication or similar drugs may be excluded

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

ASST Grande Ospedale Metropolitano Niguarda
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Milan, Italy
Azienda Ospedaliera Universitaria Citta' Della Salute E Della Scienza Di Torino
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Turin, Italy
Azienda Ospedaliera di Padova
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Padua, Italy

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Investigated drugs

Zanubrutinib is a medicine that blocks a protein called BTK in the body. This medication is being tested to see if it can help improve nerve function in people with a specific type of nerve damage caused by antibodies called anti-MAG antibodies. The study will look at whether taking this medicine for 12 months can help patients improve their ability to move, feel sensations, and perform daily activities.

Zanubrutinib

What is already known about the treatment

Zanubrutinib – Zanubrutinib is a medication taken by mouth that belongs to a class of drugs called BTK inhibitors, which work by blocking a specific protein called Bruton's tyrosine kinase that helps certain immune cells grow and survive. This medicine is used to treat various blood and immune system disorders, including specific types of nerve damage caused by abnormal antibodies (anti-MAG neuropathy), as well as certain cancers of the blood cells such as Waldenstrom macroglobulinemia, marginal zone lymphoma, and chronic lymphocytic leukemia. By blocking the BTK protein at the molecular level, zanubrutinib prevents the abnormal immune cells from multiplying and causing damage to nerves and other tissues. It is an approved medication that is currently being studied in clinical trials to better understand its effectiveness in treating nerve damage associated with abnormal protein production in the blood.

Investigated diseases

Peripheral Anti-MAG Neuropathy
A rare nerve disorder that occurs when the body produces abnormal antibodies against myelin-associated glycoprotein, a protein found in the protective covering of nerves. These antibodies gradually damage the myelin sheath, leading to progressive weakness and loss of sensation, particularly in the hands and feet. Patients typically experience numbness, tingling, and unsteadiness when walking. The condition develops slowly over months to years, causing increasing difficulty with fine motor tasks like buttoning clothes or writing. Balance problems become more pronounced as the disease progresses. The disorder is associated with abnormal protein production in the blood.
Waldenström Macroglobulinemia
A rare type of slow-growing blood cancer that affects white blood cells called B-lymphocytes. These abnormal cells accumulate in the bone marrow and produce large amounts of an abnormal protein called IgM antibody. The excess protein thickens the blood and can cause various symptoms throughout the body. Patients may experience fatigue, weakness, bleeding problems, and swollen lymph nodes. The condition can affect multiple organs as abnormal cells spread and the thick blood impairs circulation. Some patients may also develop nerve damage due to the abnormal proteins.
Marginal Zone Lymphoma
A slow-growing type of cancer that develops from B-lymphocytes in specific areas of lymphoid tissue called marginal zones. These abnormal cells multiply gradually and accumulate in lymph nodes, spleen, or other organs. The disease progresses slowly over time, often without causing symptoms in early stages. As it advances, patients may notice swollen lymph nodes, enlarged spleen, fatigue, and weight loss. The abnormal cells can spread to various parts of the body including the bone marrow. Some patients may develop abnormal protein production in their blood.
Chronic Lymphocytic Leukemia
A type of blood cancer characterized by the slow accumulation of abnormal white blood cells called lymphocytes in the blood and bone marrow. These cancerous cells gradually crowd out healthy blood cells over months or years. Many patients have no symptoms initially and the disease is discovered through routine blood tests. As it progresses, individuals may experience swollen lymph nodes, fatigue, frequent infections, and easy bruising. The abnormal cells can spread to the spleen and liver, causing these organs to enlarge. The disease typically advances slowly compared to other types of leukemia.
Monoclonal Gammopathy of Undetermined Significance
A condition where the body produces an abnormal protein called monoclonal protein or M protein in the blood. This occurs when a single clone of plasma cells in the bone marrow makes too much of one specific antibody. Most people with this condition have no symptoms and it is usually discovered during routine blood tests. The abnormal protein level remains stable in many cases without causing health problems. However, the condition requires monitoring as it can sometimes progress over time. The presence of M protein does not immediately affect body functions but indicates an abnormality in protein production.