Mycophenolate Mofetil in Systemic Sclerosis

This is an interventional treatment trial for Diffuse Cutaneous Systemic Sclerosis focused on measuring Scleroderma Read More

Inclusion Criteria:

• Must meet the American College of Rheumatology criteria for systemic sclerosis with diffuse cutaneous disease or muscle involvement
• Patients must also meet one of the following criteria:

SKIN SUBSTUDY (20 patients)

• Be within 1 1/2 years of first non-Raynaud's disease manifestation.
• How progression of skin disease at some time over the past 6 months prior to study entry based on either documented increase in skin score or new areas of skin involvement or progression (no more than 10 patients total recruited)

OR, MUSCLE SUBSTUDY (10 patients)

• Have a serum creatinine phosphokinase (CK) greater than 2 times the upper limit of normal

  • Patients entering the study on the basis of elevated CK must also have subjective and/or objective weakness; clinical evidence of cardiac, pulmonary or gastrointestinal disease as a complication of the patient¿s systemic sclerosis; or progressive skin disease.
  • The total number of patients entered in criteria 2a and 2b (skin substudy) will be 20. Patients meeting both criteria 2c. and either 2a or 2b will first be recruited into the muscle substudy (by criteria 2c) until 10 patients have been recruited.
  • Male or female patients >18 years of age.
  • Able and willing to give written informed consent and comply with the requirements of the study protocol
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for 6 weeks after completion of treatment.
  • Adequate renal function as indicated by Cr less than or equal to 3.0
  • Adequate liver function, as indicated by SGOT and SGPT less than 2.5 times the upper limit of normal.
  • Negative serum pregnancy test (for women of child bearing age)

Exclusion Criteria:

• Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer).
• Ongoing use of high dose steroids (>10mg/day) or unstable steroid dose in the past 4 weeks.
• Receipt of a live vaccine within 4 weeks prior to randomization.
• Previous Treatment with MMF
• Treatment with immunosuppressive, cytotoxic or anti-fibrotic drug within 4 weeks of screening other than anti-malarial. This includes cyclophosphamide, azathioprine (Immuran), methotrexate or other immunosuppressive or cytotoxic medication.
• Treatment with cholestyramine within 1 week of trial entry.
• History of HIV, Hepatitis B and/or Hepatitis C, or evidence of Hepatitis B or C at screening.
• Moderate to severe hepatic impairment, Child-Pugh Class B or C.
• History of recurrent significant infection or history of recurrent bacterial infections.
• Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening.
• Active gastrointestinal bleeding within 4 weeks of study entry or active serious gastrointestinal disease.
• Pregnancy (a negative serum pregnancy test will be performed for all women of childbearing potential within 14 days of treatment).
• Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• A history of phenylketonuria, hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase, Lesch-Nyhan or Kelley-Seegmiller syndrome
• Allergy to polysorbate 80/Tween
• Subjects who are breastfeeding
• Moderately severe renal dysfunction as indicated by Cr >3.0, dipstick protein >3+, or patient on dialysis.
• Hemoglobin: < 8.5 gm/dL
• Platelets: < 100,000/mm
• AST or ALT >2.5 x Upper limit of normal unless related to muscle disease.