SHS_280149 MEAP CUMI 14193
A Phase 2 Study to Evaluate Subcutaneous Abatacept vs. Placebo in Diffuse Cutaneous Systemic Sclerosis- a Double-blind, Placebo-controlled, Randomized Controlled Trial
The study hypothesis is that SC abatacept is safe and shows evidence of efficacy (improvement in modified Rodnan score [mRSS]) in patients with diffuse cutaneous systemic sclerosis (dcScc) compared to matching placebo.
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 ≤ 25 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. 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.
Rheumatic disease other than dcSSc; 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. 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. 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). 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.
Philip Mease, M.D.
University of Michigan