Abatacept for the Treatment of Myositis-associated Interstitial Lung Disease

This is a proof of concept study to evaluate the efficacy, safety and tolerability of
abatacept in Syn-ILD in a multi-center randomized, placebo-controlled 6-month (24-week) pilot
study.

Inclusion Criteria:

1. Age ≥ 18 years.

2. 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.

3. 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.

4. Active ILD (see Section 4.2).

5. Baseline FVC % <80% as minimal threshold of ILD severity (PFT done within last 3
months is acceptable for inclusion criteria determination).

6. SOC immunosuppressive therapy (IS) therapy:

1. 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.

2. 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.

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

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

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

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

9. 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.

10. 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

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

12. Subject has provided written informed consent.

Exclusion Criteria:

A patient will be excluded if any of the following Exclusion Criteria are met:

1. Severe end stage lung disease:

1. FVC ≤30% or Forced expiratory volume (FEV1) ≤ 30% or

2. Requirement of high O2 requirement ≥ 6 L/min at rest for >1 month before the
study enrollment or

3. Listed for lung transplantation or

4. PI feels that ILD is severe and end stage fibrosis is such that there is low
potential for improvement with any disease modifying intervention.

2. Subjects under the age of 18.

3. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
or other infections (including but not limited to tuberculosis and atypical
mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal
infections of nail beds).

4. Any major episode of infection requiring hospitalization or treatment with IV
antibiotics within 4 weeks of screening.

5. Active tuberculosis (TB) requiring treatment within the previous 3 years. Patients
should be screened for latent TB using purified protein derivative (PPD)/or
quantiferon gold within last 1 year and, if positive, treated following local practice
guidelines prior to initiating abatacept (ABT). Patients treated for active
tuberculosis with no recurrence in 3 years are permitted.

6. Primary or secondary immunodeficiency (history of or currently active) unless related
to primary disease under investigation.

7. Pregnant women or nursing (breast feeding) mothers.

8. History of alcohol, drug or chemical abuse within 1 year prior to screening or any
medical condition or physical or psychological state that the PI feels would not allow
the subject to safely complete the study.

9. Major surgery (including joint surgery) within 8 weeks prior to screening or planned
major surgery within 6 months following randomization.

10. Treatment with any other investigational agent within 4 weeks (or 5 half-lives of the
investigational drug, whichever is longer) of screening.

11. Previous treatment with the following cell-depleting therapies, including
investigational agents or approved therapies: CAMPATH, anti-CD4, anti-CD5, and
anti-CD3.

12. Previous treatment with ABT.

13. History of severe allergic or anaphylactic reactions to monoclonal antibodies.

14. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, renal,
hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal
disease (including complicated diverticulitis, ulcerative colitis, or Crohn's
disease.)

15. Evidence of concomitant lung disease which PI feels may interfere with clinical
assessment of ILD for example severe active chronic obstructive pulmonary disease
(COPD), asthma, occupational lung disease, pulmonary sarcoidosis, etc.

16. Prisoners or subjects who are compulsory detained