Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis
Condition: Lung Diseases, Interstitial; Systemic Sclerosis; Scleroderma
MeSH terms: Lung Diseases; Pulmonary Fibrosis; Lung Diseases, Interstitial; Scleroderma, Systemic; Scleroderma, Diffuse
Intervention: Bortezomib; Placebo; Mycophenolate mofetil
Intervention description: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks; Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks; Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks
Intervention MeSH terms: Mycophenolic Acid; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: mycophenolate; lung scarring

Summary:

      The purpose of this study is to look at whether bortezomib, mycophenolate or the combination
      of both is better to treat scarring of the lung caused by Systemic Sclerosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Meet established criteria for diffuse or limited systemic sclerosis (SSc) and evidence
             of pulmonary at high risk of progression with or without progressive skin disease.

          -  Definition includes subjects who meet the American College of Rheumatology criteria
             for scleroderma

          -  High Risk of disease progression (see rationale) will be defined as follows

          -  If first non-Raynaud's manifestation of SSc < 36 months, then if any of the following
             are true: FVC <70% predicted or high-resolution computed tomography (HRCT) maximum
             fibrosis score >3 or FVC < 85% and modified Rodnan skin score (mRSS) increase > 5 over
             6 months Regardless of disease duration

          -  Fall in FVC > 10% over the preceding 12 months or less in the absence of prior therapy
             or another identified causative process as assessed by the primary scleroderma
             physician

          -  Fall in FVC > 10% over 6 months on at least 12 months of prior therapy

          -  Age > 18 years

          -  Ability to give informed consent.

          -  Willingness to discontinue present therapy for the duration of the study

          -  Female subject is either post-menopausal or surgically sterilized or willing to use an
             acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
             device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
             duration of the study.

          -  Male subject agrees to use an acceptable method for contraception for the duration of
             the study.

          -  No evidence of acute infection

          -  Absolute neutrophil count >1000

          -  Platelets >75,000

          -  Stable mycophenolate mofetil dose for 16 weeks

        Exclusion Criteria:

          -  Inability to give informed consent or comply with protocol procedures

          -  FVC < 40% or diffusing capacity of carbon monoxide (DLCO) <30% predicted

          -  Patient has a platelet count of less than 50,000 within 14 days before enrollment.

          -  Patient has an absolute neutrophil count of less 1000 within 14 days before
             enrollment.

          -  Patient has a calculated or measured creatinine clearance of < 20 ml/minute within 14
             days before enrollment.

          -  Patient has Grade 2 peripheral neuropathy by history within 14 days before enrollment.

          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Prior to study entry, any ECG
             abnormality at Screening has to be documented by the investigator as not medically
             relevant.

          -  Patient has hypersensitivity to bortezomib, boron or mannitol.

          -  Female subject is pregnant or breast-feeding. Confirmation that the subject is not
             pregnant must be established by a negative serum -human chorionic gonadotropin (- hCG)
             pregnancy test result obtained during screening. Pregnancy testing is not required for
             post-menopausal or surgically sterilized women.

          -  Patient has received other investigational drugs within 4 weeks before enrollment

          -  Serious medical co-morbidity which in the opinion of the investigator makes
             participation in the study too high risk

          -  Psychiatric illness likely to interfere with participation in this clinical study.