Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension

This study is a randomized, placebo-controlled, double-blind phase 2 trial of patients with
dcSSc or SSc-PAH. Twenty participants with SSc-PAH and 14 participants with dcSSc will be
randomized to receive either oral ifetroban daily or matching placebo. Study participants
will be treated for 12 months, followed by a 30-day follow-up period. The study will test
whether ifetroban is safe and statistically superior to placebo in reducing the effects of
their disease at month 12 and explore the ability of ifetroban to prevent or reverse
progression in patients with early disease duration and reverse established disease in
patients with longer disease duration.

Inclusion Criteria:

Diffuse Cutaneous Criterion:

1. Systematic Sclerosis (SSc), as defined using the 2013 American College of Rheumatology/
European Union League Against Rheumatism Classification Criteria and dcSSc within 7 years
following initial diagnosis as defined by the onset of the first non-Raynaud symptom.

SSc-PAH Criteria:

1. Adults fulfilling the 2013 American College of Rheumatology/ European Union League
Against Rheumatism Classification Criteria with confirmed SSc-PAH (limited or dcSSc)
confirmed via previous cardiac catheterization

2. Stable oral therapy for PAH for at least 30 days (monotherapy or combination)

3. New York Heart Association (NYHA) Class I-III Heart Failure

Exclusion Criteria:

1. Have a diagnosis of systemic sclerosis sine scleroderma;

2. Be less than 18 years of age or greater than or equal to 80 years of age;

3. Be pregnant, nursing, or planning to become pregnant;

4. Current or planned treatment with prostanoid therapy;

5. Current or planned treatment with pirfenidone;

6. Use of rituximab in the last 3 months;

7. Use of mycophenolic acid (Myfortic, CellCept) at a stable dose for less than 3 months;

8. Current or planned corticosteroid therapy greater than 15mg per day of prednisone or
prednisone equivalent;

9. Significant lung disease, defined as FVC < 50% predicted or DLCO <40% predicted;

10. Significant kidney disease, defined as Glomerular Filtration Rate (GFR) < 60 ml/min;

11. Have moderate or severe hepatic impairment;

12. Contraindication to MRI (e.g., implanted magnetic material, claustrophobia);

13. Known hypersensitivity to gadolinium;

14. Any cause of pulmonary hypertension other than World Health Organization (WHO) Group I
associated with SSc;

15. Use of aspirin > 81 mg per day in the last two weeks;

16. Use of warfarin, heparin or other anticoagulants in the last 30 days;

17. Recent (within 6 weeks) myocardial infarction or persistent atrial arrhythmias;

18. Have a history of allergy or hypersensitivity to ifetroban;

19. Have taken investigational drugs within 30 days before study treatment administration;

20. Inability to understand the requirements of the study, inability to understand spoken
English and abide by the study restrictions and to return for the required treatments
and assessments;

21. Be otherwise unsuitable for the study, in the opinion of the investigator.