A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis
Condition: Diffuse Cutaneous Systemic Sclerosis
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis
Intervention: Abatacept; Placebo
Intervention description: Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks; 125 mg of Placebo
Intervention MeSH terms: Abatacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 88.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Scleroderma

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of Systematic Sclerosis (SSc), as defined using the 2013 American College of
             Rheumatology/ European Union League Against Rheumatism classification of SSc

          2. Diffuse Systemic Sclerosis (dcSSc) as defined by LeRoy and Medsger

          3. Disease duration of ≤ 36 months (defined as time from the first non-Raynaud phenomenon
             manifestation)

          4. For disease duration of ≤ 18 months: ≥ 10 and ≤ 35 mRSS units at the screening visit

          5. 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

          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.

        Exclusion Criteria:

          1. Rheumatic disease other than dcSSc; it is acceptable to include patients with
             fibromyalgia and scleroderma-associated myopathy

          2. Limited cutaneous systemic sclerosis or sine scleroderma at the screening visit

          3. Major surgery (including joint surgery) within 8 weeks prior to screening visit

          4. Infected ulcer prior to randomization

          5. Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the
             investigational drug, whichever is longer) of the baseline visit

          6. 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

          7. Anti-CD20, and cyclophosphamide within 12 months prior to baseline visit.

          8. Use of Intravenous Immunoglobulin (IVIG) within 12 weeks prior to baseline visit

          9. Previous treatment with chlorambucil, bone marrow transplantation, or total lymphoid
             irradiation

         10. Immunization with a live/attenuated vaccine within ≤ 4 weeks prior to the baseline
             visit

         11. Treatment with methotrexate, hydroxychloroquine, cyclosporine A, azathioprine,
             mycophenolate mofetil rapamycin, colchicine, or D-penicillamine, within≤ 4 weeks prior
             to the baseline visit

         12. Treatment with etanercept within ≤ 2 weeks, infliximab, certolizumab, golimumab, ABA
             or adalimumab within ≤ 8 weeks, anakinra within ≤ 1 week prior to the baseline visit

         13. Pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin ) ≤
             40% of predicted at the screening visit

         14. 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.

         15. 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).

         16. Positive for hepatitis B surface antigen prior to the baseline visit

         17. 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

         18. 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).

         19. 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

         20. Severe skin thickening (mRSS 3) on the inner aspects of thighs, upper arms, or abdomen

         21. Patients with a history of anaphylaxis to abatacept