A MultiCenter Study of Combined PEX, Rituximab, and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations

This is a randomized, multi-center, open-label Phase II clinical trial to determine the
efficacy of combined plasma exchange (PEX), rituximab, and conventional corticosteroid
administration, in comparison to corticosteroids alone, among patients with acute IPF
exacerbations.

INCLUSION CRITERIA:

1. A diagnosis of idiopathic pulmonary fibrosis that fulfills American Thoracic Society
Consensus Criteria.1

2. Unexplained worsening or development of dyspnea or hypoxemia within the preceding 30
days.

3. Radiographic imaging showing ground-glass abnormality and/or consolidation
superimposed on a reticular or honeycomb pattern consistent with UIP.

EXCLUSION CRITERIA

1. Diagnosis of documented infection, thromboembolic disease, an additional etiology for
acute lung injury/adult respiratory distress syndrome, congestive heart failure.

2. Presence of active hepatitis B infection.

3. Coagulopathy defined as an INR > 1.8, PTT > 2 x control, and platelet count < 50K.

4. Hyperosmolar state or diabetic ketoacidosis to suggest uncontrolled diabetes mellitus
or uncontrolled hypertension.

5. Hemodynamic instability.

6. History of reaction to blood products, murine-derived products, or prior exposures to
human-murine chimeric antibodies,

7. History of malignancy.

8. Unwillingness to accept a blood transfusion.

9. Unwillingness to agree to full supportive medical care (e.g., intubation) for up to 2
weeks after enrollment.

10. Inability or unwillingness to complete post-treatment surveillance for 60 days.

11. Diagnosis of major comorbidities expected to interfere with subjects study
participation for 28 days.

12. Treatment for >5 days within the preceding month with >20 mg prednisone (or
equivalent dose corticosteroid) or any treatment during the preceding month with a
potent cellular immunosuppressant (e.g., cyclophosphamide, methotrexate,
mycophenolate, azathiaprine, calcineurin inhibitors, etc.) unless the patient has a
BAL negative for opportunistic pathogens (e.g, Pneumocystis, viruses, intracellular
organisms, mycobacteria, etc.).

13. Current treatment with an angiotensin converting enzyme inhibitor that cannot be
discontinued and/or substituted with another antihypertensive agent (to minimize
potential hemodynamic complications during PEX).