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

Must not have

Known active hematologic blood-related disorder other than anemia of chronic disease or iron deficiency anemia

Evidence of clinically significant pulmonary hypertension or left ventricular dysfunction with left ventricular ejection fraction < 40% from either prior heart catheterization or resting transthoracic echocardiography within the preceding 6 months.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 7 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing ixazomib, an oral medication, to see if it can help people with a specific type of scleroderma that affects their skin and lungs. The drug works by reducing inflammation and preventing tissue damage. Participants will take the medication for an extended period to assess its safety and effectiveness.

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.

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.

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

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

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I have been diagnosed with diffuse cutaneous systemic sclerosis.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a blood disorder that is not chronic anemia or iron deficiency.

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My heart's pumping ability is reduced, with an ejection fraction below 40%.

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I have used rituximab before.

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I have a narrowing in my esophagus that makes it hard to swallow pills.

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My kidneys are not working well, with a creatinine clearance below 30 mL/min.

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I have previously taken ixazomib or similar medications.

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I have used cyclophosphamide before.

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I am not using medications that strongly affect liver enzyme activity.

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I haven't had serious heart problems or hospital visits for heart issues in the last 6 months.

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I have a known blood cancer.

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I have had a stem cell or bone marrow transplant.

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I am receiving treatment for high blood pressure in the lungs.

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My liver tests show significant abnormalities.

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I have a connective-tissue disorder like rheumatoid arthritis or lupus.

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I have had a scleroderma renal crisis before.

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I do not have severe nerve damage that could worsen with ixazomib treatment.

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I do not have any active infections like bronchitis or UTI.

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I am currently using or will use certain medications that affect my immune system or blood pressure.

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I do not have severe lung problems like COPD, emphysema, or serious asthma.

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I have or might have an active stomach ulcer.

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I have a known liver condition like hepatitis or cirrhosis.

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

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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 study objectives

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

29%

Diarrhoea

24%

White blood cell count decreased

20%

Platelet count decreased

16%

Rash

16%

Neutrophil count decreased

11%

Pneumonia

Constipation

Malaise

Pyrexia

Anaemia

Nasopharyngitis

Decreased appetite

Taste disorder

Acute kidney injury

Influenza

Bile duct stone

Gastroenteritis

Pneumonia bacterial

Bone pain

Febrile neutropenia

Duodenal ulcer

Enterocolitis

Tibia fracture

Interstitial lung disease

Prinzmetal angina

Compression fracture

Spinal compression fracture

Tumour lysis syndrome

100%

80%

60%

40%

20%

Study treatment Arm

[Overall]; Combination Therapy + Ixazomib Therapy

[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy

[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

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

~3510

0 / 23Eligibility 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.

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Who is running the clinical trial?

Michael M. PhamLead Sponsor

W. Leroy GriffingLead Sponsor

Michael Pham, MDPrincipal InvestigatorMayo Clinic

1 Previous Clinical Trials

486 Total Patients Enrolled

Leroy Griffing, MD5.011 ReviewsPrincipal Investigator - Mayo Clinic

Mayo Clinic

5Patient Review

I felt extremely confident in this doctor's ability after our consultation. They have excellent bedside manner and made sure I was comfortable with the information they were sharing with me. I would definitely recommend them to anyone seeking a great physician.