What is the mechanism of action of this treatment?

Ixazomib, a proteasome inhibitor, works by blocking the proteasome's ability to degrade proteins, leading to the accumulation of defective proteins within cells, which can induce cell death, particularly in rapidly dividing cells such as those involved in autoimmune responses. This mechanism is significant for systemic scleroderma patients as it may help reduce the overactive immune response and fibrosis characteristic of the disease. Other common treatments include immunosuppressants like methotrexate and mycophenolate mofetil, which inhibit the proliferation of immune cells, and antifibrotic agents like nintedanib, which block pathways involved in tissue scarring. These mechanisms are crucial as they target the underlying processes of immune dysregulation and fibrosis, potentially improving symptoms and slowing disease progression in systemic scleroderma patients.

What side effects are associated with this type of intervention?

Common treatments for systemic scleroderma include immunosuppressive agents like cyclophosphamide, methotrexate, and mycophenolate mofetil. These treatments can have side effects such as increased risk of infections, liver toxicity, gastrointestinal issues, and bone marrow suppression. Proteasome inhibitors like Ixazomib, which are being studied for their effects on scleroderma-related lung disease, may cause side effects including gastrointestinal disturbances, peripheral neuropathy, and hematologic toxicities such as thrombocytopenia and anemia.

What prior FDA approvals exist?

As of now, there are no FDA-approved proteasome inhibitors specifically for the treatment of systemic scleroderma. However, treatments for systemic scleroderma generally include immunosuppressive agents such as methotrexate, mycophenolate mofetil, and cyclophosphamide. These drugs help manage symptoms and slow disease progression by modulating the immune system. Additionally, newer biologic agents and targeted therapies are being explored in clinical trials to provide more effective treatment options.

What other types of research exist?

Promising novel alternatives to Ixazomib for Systemic Scleroderma patients in 2024 may include biologics such as Rituximab (a B-cell depleting agent) and Tocilizumab (an IL-6 receptor antagonist), which have shown efficacy in systemic sclerosis. Additionally, Nintedanib, a tyrosine kinase inhibitor, has been approved for treating interstitial lung disease associated with systemic sclerosis and could be considered.

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Proteasome Inhibitor

Ixazomib for Scleroderma-Related Lung Disease

Phase 2

Waitlist Available

Led By Michael Pham, MD

Research Sponsored by Michael M. Pham

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Scleroderma skin thickness score (modified Rodnan skin score) between 15 and 45

Confirmed diagnosis of diffuse cutaneous systemic sclerosis/scleroderma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 7 months

Awards & highlights

Study Summary

This trial is testing a new medication for scleroderma/systemic sclerosis to see if it is safe and effective.

Who is the study for?

Adults over 18 with a confirmed diagnosis of diffuse cutaneous systemic sclerosis/scleroderma, experiencing lung involvement but without severe heart or kidney issues, not currently smoking, and who haven't had certain treatments like stem cell transplants. Participants should have stable disease without expectation of needing to drop out due to other health problems.Check my eligibility

What is being tested?

The trial is testing the oral medication Ixazomib for its safety and effects on skin, lungs, and overall health in scleroderma-related lung disease patients. It aims to understand how well patients tolerate this drug and its impact on their quality of life.See study design

What are the potential side effects?

Ixazomib may cause side effects such as gastrointestinal issues (like nausea), blood count abnormalities (affecting red or white cells), potential liver function changes, nerve damage (neuropathy), and could worsen any existing infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My skin thickness score for scleroderma is between 15 and 45.

Select...

I have been diagnosed with diffuse cutaneous systemic sclerosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 7 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~7 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 7 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Change in the UCLA Scleroderma Clinical Trials Consortium Gastrointestinal 2.0 (UCLA SCTC GIT 2.0) questionnaire score

Number of participants with at least one treatment-emergent adverse event (AE)

Number of participants with treatment-emergent AEs leading to ixazomib dose modifications.

+1 more

Secondary outcome measures

Change from baseline in Modified Rodnan Skin Score (MRSS)

Change from baseline in high resolution chest CT scan Goh score

Diffuse Scleroderma

+7 more

Side effects data

From 2021 Phase 4 trial • 45 Patients • NCT03416374

67%

Rash

50%

Diarrhoea

50%

Decreased appetite

33%

Nasopharyngitis

33%

Taste disorder

33%

White blood cell count decreased

17%

Bone pain

17%

Compression fracture

17%

Constipation

17%

Malaise

17%

Tibia fracture

17%

Neutrophil count decreased

17%

Anaemia

17%

Pyrexia

17%

Platelet count decreased

17%

Spinal compression fracture

100%

80%

60%

40%

20%

Study treatment Arm

[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy

[Overall]; Combination Therapy + Ixazomib Therapy

[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy

Trial Design

1Treatment groups

Experimental Treatment

Group I: Ixazomib in patients with scleroderma-interstitial lung disease (ILD)Experimental Treatment1 Intervention

Participants will be administered oral ixazomib for six cycles (each cycle is 28 days duration).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ixazomib

2017

Completed Phase 4

~3370

0 / 2Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ixazomib, a proteasome inhibitor, works by blocking the proteasome's ability to degrade proteins, leading to the accumulation of defective proteins within cells, which can induce cell death, particularly in rapidly dividing cells such as those involved in autoimmune responses. This mechanism is significant for systemic scleroderma patients as it may help reduce the overactive immune response and fibrosis characteristic of the disease. Other common treatments include immunosuppressants like methotrexate and mycophenolate mofetil, which inhibit the proliferation of immune cells, and antifibrotic agents like nintedanib, which block pathways involved in tissue scarring. These mechanisms are crucial as they target the underlying processes of immune dysregulation and fibrosis, potentially improving symptoms and slowing disease progression in systemic scleroderma patients.

Achieving minimal disease activity in psoriatic arthritis predicts meaningful improvements in patients' health-related quality of life and productivity.Challenges in the treatment of psoriasis with biologics: vaccination, history of malignancy, human immunodeficiency virus (HIV) infection, and pediatric psoriasis.