A Randomized, Controlled Pilot Trial to Evaluate the Efficacy and Safety of Subcutaneous Abatacept in Treating Interstitial Lung Disease Associated With the Anti-synthetase Syndrome

• Age ≥ 18 years.

• Anti-synthetase syndrome defined as the patient possessing 1 antisynthetase autoantibody (Jo-1, PL-12, PL-7, KS, OJ, EJ, Zo) in the presence of autoimmune ILD.

• ILD defined by radiographic (HRCT chest) findings of reticulation, honeycombing or ground glass opacities (GGO) without another plausible explanation. HRCT chest defining ILD for inclusion criteria, should be within last 1 year done as SOC.

• Active ILD (see Section 4.2).

• Baseline FVC a) % \<80% b) FVC 80-100% with \> = 10% decline in FVC in last 12 months as minimal threshold of ILD severity (PFT done within last 3 months is acceptable for inclusion criteria determination)

• SOC immunosuppressive therapy (IS) therapy:

∙ Steroids (prednisone or other forms of steroid in equivalent doses) OR one of the other immunosuppressive agent (either Mycophenolate (MMF) or Azathioprine (AZA) OR a combination of steroid and an immunosuppressive agent. MMF (maximum of 3 gm/day) or azathioprine (maximum of 200 mg/day).Goal is to start the trial drug (or placebo) soon after starting SOC (MMF/AZA/Steroids) and their doses are stable. Note that patients on steroids alone as well as not on steroids can be enrolled in the trial as well.

‣ Desired dose of the SOC therapy should be reached 4 weeks prior to first study visit (Visit 1). No dose changes are allowed 4 weeks prior to first study visit.

‣ Dose of concomitant therapy (SOC) cannot be changed during the 24 weeks of the trial unless safety/toxicity issues supervene.

‣ If on steroid, the steroid dose must be stable for 2 weeks prior to Visit 1.

• No other concomitant IS medications including methotrexate, cyclosporine, intravenous immunoglobulin (IVIG), tacrolimus, cyclophosphamide or tofacitinib.

• No concomitant biologic agents (i.e. rituximab, anti-tumor necrosis factor (TNF) agents, tocilizumab).

• Additional IS therapy: Patient cannot begin any new IS therapy or new steroid taper for the 24-week study period, except if severe clinical worsening (flare up) of the disease requiring rescue therapy occurs (i.e. documentation of worsening of PFT/HRCT and patient and physician determination of worsening). See section of rescue medication below for details.

⁃ If the enrolling physician is planning to discontinue current IS agent or steroid before clinical trial, then following washout period is required prior to Visit 1.

⁃ Medication Washout Period methotrexate 4 weeks Other IS agent (e.g. azathioprine, cyclosporine, tacrolimus, leflunomide, mycophenolate mofetil) 4 weeks IVIg or cyclophosphamide 3 months rituximab 6 months infliximab or adalimumab 8 weeks glucocorticoids 2 weeks etanercept 2 weeks anakinra 1 week pirfenidone 4 weeks

⁃ Men and women of reproductive potential must agree to use an acceptable method of birth control during the trial period.

⁃ Subject has provided written informed consent.