Zanubrutinib for Immunoglobulin-Related Disease

Overseen By Angie R Aberia, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Matthew C. Baker

Must be taking: Glucocorticoids

Must not be taking: DMARDs, Cytotoxics, Biologics, others

Disqualifiers: Autoimmune diseases, Active infections, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is evaluating whether zanubrutinib (Brukinsa) is safe and effective for individuals with IgG4-related disease. This condition causes swelling and damage in organs such as the salivary and tear glands. The trial includes individuals with a doctor-confirmed diagnosis. Participants should not use certain immune-suppressing drugs but may continue a stable dose of prednisone. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot be on immunosuppressive drugs other than prednisone, and you must not have used certain other medications like DMARDs, BTK inhibitors, or biologic agents within specific time frames before starting the trial.

Is there any evidence suggesting that zanubrutinib is likely to be safe for humans?

Research has shown that zanubrutinib, the treatment being tested, has a safety profile similar to other drugs targeting specific proteins in cells. Studies have found that zanubrutinib's side effects align with expectations for this type of drug. In earlier research, nearly 70% of patients taking zanubrutinib experienced some side effects, which were generally similar to those seen with other similar treatments.

Overall, zanubrutinib is considered well-tolerated, with predictable side effects for this kind of drug. While this trial continues to explore its use for IgG4-related disease, existing data provides a reassuring picture of its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Zanubrutinib is unique because it selectively targets and inhibits Bruton's tyrosine kinase (BTK), a key player in the signaling pathways of B cells, which are often involved in immunoglobulin-related diseases. Unlike current treatments that may not specifically target BTK, zanubrutinib's precision could lead to fewer side effects and more effective disease control. Researchers are excited about this treatment because its targeted approach may offer a new level of precision in managing these conditions, potentially improving patient outcomes and quality of life.

What evidence suggests that zanubrutinib might be an effective treatment for IgG4-related disease?

Studies have shown that zanubrutinib can effectively treat certain diseases. For instance, it maintained or improved health in 96% of patients who switched from another treatment for WM disease, a type of blood cancer. Research has also found that zanubrutinib can extend the time patients remain without disease progression compared to some other treatments. Although information on its effects on IgG4-related disease is limited, its success in other conditions is encouraging. This trial will evaluate zanubrutinib's potential to manage symptoms or slow disease progression in patients with IgG4-related disease. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults aged 18-85 with confirmed IgG4-related disease affecting the submandibular or lacrimal glands can join. They must not be on certain immunosuppressants, except for a stable dose of prednisone. Women need a negative pregnancy test and agree to birth control use.

Inclusion Criteria

All women must test negative for pregnancy and agree to use a reliable method of birth control

Presence of a lymphoplasmacytic infiltrate with 10 IgG4+ plasma cells per high-power field and/or an IgG4+/IgG+ plasma cell ratio of 40%

My IgG4-related disease in the salivary or tear glands is confirmed by a biopsy.

Exclusion Criteria

I haven't taken drugs like infliximab, abatacept, or tocilizumab in the last 56 days.

I haven't taken BTK inhibitors in the last 6 months.

I have not taken JAK inhibitor medication in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanubrutinib orally at a dose of 80mg BID for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zanubrutinib

Trial Overview The trial is testing Zanubrutinib's safety and effectiveness in treating IgG4-related disease. Participants will receive an 80 mg dosage to assess how well it manages their condition compared to current standard treatments.

How Is the Trial Designed?

Group I: Zanubrutinib Experimental Treatment 1 Intervention

Zanubrutinib orally at a dose of 80mg BID for 24 weeks

Zanubrutinib is already approved in United States, China for the following indications:

Approved in United States as Brukinsa for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)

Approved in China as Brukinsa for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)

Who Is Running the Clinical Trial?

Matthew C. Baker

Lead Sponsor

Trials

2

Recruited

10+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK600004/

Clinical Review - Zanubrutinib (Brukinsa) - NCBI - NIH The majority of patients (zanubrutinib versus ibrutinib) achieved a PR (78.6% versus 69.8%), followed by a CR (6.7% versus 5.5%), a nodular PR (0.9% versus 0.0 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04602598

Zanubrutinib in Patients With IgG4-Related Disease This will be a single-site, open-label study in symptomatic patients with IgG4-related disease affecting the submandibular and/or lacrimal glands.

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK595393/

Clinical Review - Zanubrutinib (Brukinsa) - NCBI - NIH Efficacy Results​​ Compared to DRC, zanubrutinib was associated with significantly longer PFS (HR = 0.35; 95% CI, 0.14 to 0.86) after weighting. The HR for OS ...

4. ashpublications.org ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024015596/547194/Outcomes-following-transition-from-ibrutinib-to

Outcomes following transition from ibrutinib to zanubrutinib in ... WM disease response was maintained or improved in 96% (44/46) of efficacy-evaluable patients (n = 2 converted to negative immunofixation). While ...

5. targetedonc.com targetedonc.com/view/five-year-follow-up-confirms-zanubrutinib-as-a-frontline-option-in-cll-sll

Five-Year Follow-Up Confirms Zanubrutinib as a Frontline ... Zanubrutinib demonstrated sustained progression-free survival vs bendamustine/rituximab at 5 years in treatment-naive chronic lymphocytic leukemia/small ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK594329/

Zanubrutinib (Brukinsa) - NCBI Bookshelf pERC discussed the safety profile of zanubrutinib and considered it aligned with the known safety profile of BTK inhibitors. Overall, the incidence of AEs and ...

7. ema.europa.eu ema.europa.eu/en/documents/variation-report/brukinsa-h-c-004978-ii-0003-epar-assessment-report-variation_en.pdf

Brukinsa, INN-zanubrutinib - EMA The E–R relationship was assessed between zanubrutinib exposure metrics (AUCss, Cmax,ss, and Cmin,ss) and safety endpoints, including AEs ...

8. ashpublications.org ashpublications.org/bloodadvances/article/6/4/1296/477740/Pooled-safety-analysis-of-zanubrutinib-monotherapy

Pooled safety analysis of zanubrutinib monotherapy in ... Pooled safety data from zanubrutinib monotherapy studies in B-cell malignancies are consistent with the toxicity profile of BTK inhibitors.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-02265

Median 5-Year Follow-Up of SEQUOIA The safety profile of zanubrutinib was consistent with that observed in the primary analysis. Almost 70% of zanubrutinib-treated patients ...

10. acrabstracts.org acrabstracts.org/abstract/a-phase-ii-single-site-open-label-study-of-zanubrutinib-in-patients-with-igg4-related-disease/

A Phase II, Single-Site, Open-Label Study of Zanubrutinib ... In this phase 2 proof-of-concept study (NCT04602598), we report the efficacy and safety of zanubrutinib in patients with IgG4-RD affecting the lacrimal and/or ...