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A Study to Evaluate the Safety and Tolerability of Oral Ixazomib in Scleroderma-related Lung Disease Patients

Study Purpose

The purpose of this research study is to learn about the effects of the medication ixazomib in participants with scleroderma/systemic sclerosis including its safety and tolerability, its effects on skin, lungs and other organs, and its effects on overall health and quality of life.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Male and female patients, age ≥18 years at time of signing informed written consent.
  • - Confirmed diagnosis of diffuse cutaneous systemic sclerosis/scleroderma.
  • - Disease duration not longer than 60 months defined as the time from the first non-Raynaud phenomenon manifestation.
  • - Scleroderma skin thickness score (modified Rodnan skin score) between 15 and 45.
  • - Evidence of scleroderma-related lung involvement on chest CT scan completed within the preceding 3 months or at screening study visit.
  • - Pulmonary function testing demonstrating FVC ≥45% predicted and DLCO ≥40% predicted at screening study visit.
  • - Resting transthoracic echocardiogram within the preceding 6 months or at screening study visit without evidence of pulmonary artery hypertension.
  • - Stable mycophenolate dose during the preceding 3 months for those who are taking mycophenolate.
Mycophenolate use is not an eligibility requirement to participate; but those participants already using mycophenolate at screening study visit will continue taking the medication throughout the entire study.
  • - Willingness to undergo supervised withdrawal during the first 90 days of the study of any other medication besides mycophenolate used specifically as treatment of scleroderma-related interstitial lung disease with confirmed stable pulmonary status.
  • - Willingness to undergo supervised withdrawal during the first 90 days of the study of any other prohibited medications with confirmed stable status.
  • - Able to understand and sign a written informed consent form.
  • - Able to understand the importance of adhering to study treatment and the study protocol, and willing and able to follow all study requirements, including the concomitant medication restrictions, throughout the study.
  • - Practice birth control requirements for sexually active female participants including option of abstinence for the entire study and for at least 90 days after the last dose of study medication.
  • - Practice birth control requirements for sexually active male participants or partners including option of abstinence for the entire study and for at least 90 days after the last dose of study medication.

Exclusion Criteria:

  • - Pulmonary artery hypertension under treatment.
  • - 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.
  • - Evidence of significant gastrointestinal involvement by scleroderma as assessed by the University of California, Los Angeles, Scleroderma Clinical Trial Consortium Gastrointestinal Tract multi-item questionnaire, 2.0 ([UCLA SCTC GIT 2.0) at screening study visit.
  • - Known esophageal stricture sufficient to limit the ability to swallow oral medication.
  • - Prior history of scleroderma renal crisis.
  • - Another connective-tissue disorder (eg, rheumatoid arthritis, systemic lupus erythematosus) - Any other significant pulmonary disorder (e.g., chronic obstructive pulmonary disease, emphysema, adult moderate to severe asthma) - Significant environmental exposure known to cause pulmonary fibrosis including, but not limited to, drugs (e.g., amiodarone), asbestos, beryllium, radiation, or domestic birds or other exposures associated with hypersensitivity pneumonitis.
  • - Unstable or deteriorating cardiac disease within the preceding 6 months including but not limited to unstable angina pectoris, myocardial infarction (heart attack), heart failure requiring hospitalization, poorly controlled heart arrhythmia, or significant pericardial effusion/fluid collection around the heart.
  • - Known liver disease (e.g., chronic hepatitis or cirrhosis) - Significant abnormality of liver function tests.
  • - Significant kidney function impairment of any cause as evidenced by creatinine clearance <30 mL/min.
  • - Known active or suspected peptic (stomach) ulcer.
  • - Known active hematologic blood-related disorder other than anemia of chronic disease or iron deficiency anemia.
  • - Significant abnormality of blood count including hemoglobin ≤ 8.0 gm/dl, absolute neutrophil count ≤ 1000, or platelet count ≤ 75,000.
  • - Known hematologic blood-related malignancy.
  • - Prior stem cell or bone marrow transplant.
  • - History of any malignancy within the last 5 years other than non-melanoma skin cell cancer cured by local resection or a carcinoma-in-situ.
  • - Any condition likely to result in death within 12 months.
  • - Any condition which might be significantly worsened by the known side effects associated with ixazomib including known ≥ grade 2 peripheral neuropathy.
  • - Tobacco smoking within 3 months of screening study visit or unwillingness to avoid smoking throughout the study (e.g., cigarette, pipe, or cigar) - History of alcohol or substance abuse in the previous 2 years.
  • - Any active infection including, but not limited to, bronchitis, pneumonia, sinusitis, or urinary tract infection.
  • - Pregnancy or lactation/breast feeding.
  • - Expectation of study participation being interrupted on account of a foreseeable medical or surgical event.
  • - Prior use of ixazomib or other proteasome inhibitor medication.
  • - Suspected intolerance, allergy, or hypersensitivity to ixazomib or any of its excipients.
  • - Any prior use of rituximab.
  • - Any prior use of cyclophosphamide.
  • - Ongoing use within the preceding 28 days or expected use of an investigational drug (an investigational drug is defined as any drug that has not been FDA approved for marketing) - Ongoing use or expected use of any of the following therapies: Strong inducers of a cytochrome drug metabolizing enzyme in the liver (CYP3A ).
(e.g. rifampin, rifapentine, rifabutin, carbamazepine, enzalutamide, phenytoin, fosphenytoin, phenobarbital, St. John's wort)
  • - Ongoing use or expected use of any of the following medications: cyclophosphamide, rituximab, abatacept, nintedanib, tocilizumab, intravenous immunoglobulin (IVIG), methotrexate, leflunomide, azathioprine, sirolimus, tacrolimus, oral corticosteroids at a dose >10 mg/d prednisone equivalent, D-penicillamine, minocycline, interferon-γ, bosentan, ambrisentan, macitentan, phosphodiesterase inhibitors (sildenafil or tadalafil for uses other than erectile dysfunction or Raynaud phenomenon), riociguat, tumor necrosis factor-α (TNF-α) inhibitors (infliximab, etanercept, adalimumab, certolizumab, golimumab), and cyclosporine, .

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04837131
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

W. Leroy Griffing
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Leroy Griffing, MD
Principal Investigator Affiliation Mayo Clinic
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Systemic Sclerosis, Scleroderma, Diffuse Systemic Sclerosis, Diffuse Scleroderma, Diffuse Cutaneous Systemic Sclerosis, Diffuse Cutaneous Scleroderma, Progressive Systemic Sclerosis, Progressive Scleroderma, Scleroderma, Systemic, Scleroderma, Diffuse, Scleroderma;Progressive, Systemic Sclerosis, Diffuse, Systemic; Sclerosis, Progressive, Scleroderma of Lung, Scleroderma With Pulmonary Involvement, Systemic Sclerosis Pulmonary, Systemic Sclerosis With Lung Involvement, Interstitial Lung Disease, Pulmonary Fibrosis Interstitial
Study Website: View Trial Website
Additional Details

The primary objective of this study is to assess the safety and tolerability of oral ixazomib taken on days 1, 8, and 15 of each 28-day treatment cycle for 6 cycles in 12 participants having diffuse systemic sclerosis/scleroderma of less than 5 years duration with non-severe interstitial lung involvement as identified from chest CT scan completed within the preceding 3 months or at study screening visit. All 12 participants will receive oral ixazomib. Reflecting the common use of mycophenolate in the management of scleroderma with complicating interstitial lung disease, 6 of 12 participants who will be enrolled will be already taking mycophenolate at a stable dose for the preceding 3 months and will be allowed to continue taking mycophenolate throughout the entire study prescribed as routine care. Ixazomib will be added to their medications. The remaining 6 of 12 participants meeting the same eligibility criteria will not be using mycophenolate or any other treatment for scleroderma interstitial lung disease at the time of enrollment and will subsequently take ixazomib study medication during participation in this study. Ixazomib dose modification or interruption is allowed for safety and tolerability reasons at any time during the study. The secondary objective of this study is to assess the effect of ixazomib on scleroderma skin tightness/thickening and its effect on scleroderma interstitial lung disease. The study includes approximately 13 clinic visits over up to approximately 10 months. Study procedures include medical examinations, blood tests, chest CT scans, pulmonary function tests, echocardiogram, EKG, skin biopsies, and questionnaires. There is no cost for participation in this study.

Arms & Interventions

Arms

Experimental: Ixazomib in patients with scleroderma-interstitial lung disease (ILD)

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

Interventions

Drug: - Ixazomib

Ixazomib 4 mg capsule taken orally on days 1, 8, and 15 of a 28-day treatment cycle repeated for 6 cycles

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Mayo Clinic in Arizona, Scottsdale, Arizona

Status

Recruiting

Address

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259

Site Contact

Emily Branch

Branch.Emily@Mayo.edu

480-301-9392