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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 ).
- 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.
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.
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.