A Study Evaluating the Efficacy and Safety of Baricitinib in Systemic Sclerosis

Prior treatment

• Major surgery (including joint surgery) within 8 weeks prior to screening visit
• Infected ulcer prior to treatment
• 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 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 with etanercept within ≤ 2 weeks, infliximab, certolizumab, golimumab, ABA or adalimumab within ≤ 8 weeks, anakinra within ≤ 1 week prior to the baseline visit
• 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

Other illness

• Rheumatic disease other than dcSSc; it is acceptable to include patients with fibromyalgia and scleroderma-associated myopathy
• 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.
• Patients with a history of anaphylaxis to Baricitinib or cyclophosphamide

Lab values

• Pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin ) ≤ 40% of predicted at the screening visit
• Subjects at risk for tuberculosis (TB). Specifically excluded from this study will be participants 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; and latent TB that was not successfully treated (≥ 4 weeks).
• Subjects at risk for tuberculosis (TB). Specifically excluded from this study will be participants 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; and latent TB that was not successfully treated (≥ 4 weeks).
• Any of the following at the screening visit: Hemoglobin \<8 g/dL; ANC \< 1,000/mm3 (\<1 x 109/L); platelets \< 100,000/mm3 (\<100 x 109/L); serum creatinine \> 2 x ULN; serum ALT or AST \> 2 x ULN

Other

• Limited cutaneous systemic sclerosis or sine scleroderma at the screening visit
• Severe skin thickening (mRSS 3) on the inner aspects of thighs, upper arms, or abdomen

• Diagnosis of Systematic Sclerosis (SSc), as defined using the 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc
• Diffuse Systemic Sclerosis (dcSSc) 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:
  • 1)Increase ≥ 3 in mRSS units compared with the last visit within previous 1-6 months 2)Involvement of one new body area with ≥ 2 mRSS units compared with the last visit within the previous 1-6 months 3)Involvement of two new body areas with ≥ 1 mRSS units compared with the last visit within the previous 1-6 months 4)Presence of 1 or more Tendon Friction Rub 6.Age ≥ 18 years at the screening visit 7.If female of childbearing potential, the patient must have a negative pregnancy test at screening and baseline visits 8.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.
  • 9.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.