Ensayos clínicos

Inclusion Criteria

• Diagnosis of Systemic Sclerosis (SSc), as defined using the 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc
• Diffuse Systemic Sclerosis as defined by LeRoy and Medsger
• Disease duration of ≤ 36 months (defined as time from the first non−Raynaud phenomenon manifestation)
• For disease duration of ≤ 18 months, ≥ 10 and ≤ 35 mRSS units at the screening visit
• For disease duration of >18-36 months, ≥ 15 and ≤ 45 mRSS units at the screening visit and one of the following
  • Increase ≥ 3 in mRSS units compared with the last visit within previous 1-6 months
  • Involvement of one new body area with ≥ 2 mRSS units compared with the last visit within the previous 1-6 months
  • Involvement of two new body areas with ≥ 1 mRSS units compared with the last visit within the previous 1-6 months
  • Presence of 1 or more Tendon Friction Rub
• Age ≥ 18 years at the screening visit
• If female of childbearing potential, the patient must have a negative pregnancy test at screening and baseline visits
• Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent) and NSAIDs are permitted if the patient is on a stable dose regimen for
  • 2 weeks prior to and including the baseline visit
• ACE inhibitors, calcium-channel blockers, proton-pump inhibitors, and/or oral vasodilators are permitted if the patient is on a stable dose for ≥ 2 weeks prior to and including the baseline visit

Exclusion Criteria

• Rheumatic disease other than diffuse systemic sclerosis
  • It is acceptable to include patients with fibromyalgia and scleroderma-associated myopathy
• Limited cutaneous systemic sclerosis or sine scleroderma at the screening visit
• Major surgery (including joint surgery) within 8 weeks prior to screening visit
• Infected ulcer prior to randomization
• Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of the baseline visit
• Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and ABA
• Anti-CD20, and cyclophosphamide within 12 months prior to baseline visit
• Use of Intravenous Immunoglobulin (IVIG) within 12 weeks prior to baseline visit
• Previous treatment with chlorambucil, bone marrow transplantation, or total lymphoid irradiation
• Immunization with a live/attenuated vaccine within ≤ 4 weeks prior to the baseline visit
• Treatment with methotrexate, hydroxychloroquine, cyclosporine A, azathioprine, mycophenolate mofetil rapamycin, colchicine, or D-penicillamine, within ≤ 4 weeks prior to the baseline visit
• Treatment prior to the baseline visit with
  • Etanercept within ≤ 2 weeks
  • Infliximab, certolizumab, golimumab, ABA or adalimumab within ≤ 8 weeks
  • Anakinra within ≤ 1 week
• Pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin ) ≤ 40% of predicted at the screening visit
• Pulmonary arterial hypertension (PAH) as determined by right heart catheterization or on PAH approved medications for PAH
  • It is acceptable to use PDFE-5 inhibitors for Raynaud's and digital ulcers
• Subjects at risk for tuberculosis (TB)
  • Specifically with a history of active TB within the last 3 years, even if it was treated
  • A history of active TB greater than 3 years ago, unless there is documentation that the prior anti-TB treatment was appropriate in duration and type
  • Current clinical, radiographic, or laboratory evidence of active TB
  • Latent TB that was not successfully treated (≥ 4 weeks)
• Positive for hepatitis B surface antigen prior to the baseline visit
• Positive for hepatitis C antigen, if the presence of hepatitis C virus was also shown with polymerase chain reaction or recombinant immunoblot assay prior to baseline visit
• Any of the following at the screening visit
  • Hemoglobin <8.5 g/dL
  • WBC < 3,000/mm3 (<3 x 109/L)
  • Platelets < 100,000/mm3 (<3 x 109/L)
  • Serum creatinine > 2 x ULN
  • Serum ALT or AST > 2 x ULN
• Severe skin thickening (mRSS 3) on the inner aspects of thighs, upper arms, or abdomen
• Patients with a history of anaphylaxis to abatacept