GM-CSF in Patients With Pulmonary Alveolar Proteinosis

PAP is a rare lung disease characterized by accumulation of surfactant phospholipids and
proteins within the lungs. There is no specific pharmacologic therapy for PAP and the
current practice of lung lavage under general anesthesia is invasive and has limitations.
Although it is unknown if the anti GM-CSF antibody is related to the disease pathogenesis,
observations suggest a role for GM-CSF in lung homeostasis as well as in the pathogenesis of
PAP.

Patients will receive subcutaneous GM-CSF or placebo once a day and will be followed on an
outpatient basis at 2 weeks, and 1, 2, 3, 4, 5 and 6 months after initiation of therapy.
Clinical response will determine dosing schedule and will be evaluated by symptom scores,
gas exchange data, and chest radiographs.

Inclusion criteria:

- Diagnosis of primary or idiopathic PAP

- Creatinine no greater than 2 mg/dL

- Bilirubin no greater than 2 mg/dL

- Liver enzymes no greater than 3 times normal

- Women must use an effective method of contraception, be post menopausal, or be
surgically sterilized

Exclusion criteria:

- Active respiratory infection

- Active cardiovascular disease (e.g., cardiogenic pulmonary edema)

- Underlying myeloproliferative disorder or leukemia

- Other secondary cause of PAP (e.g., occupational exposure to silica or HIV with PCP)

- At increased risk of side effects from GM-CSF therapy (i.e., rheumatoid arthritis,
immune thrombocytopenia, or autoimmune thyroiditis)

- Previous therapy with GM-CSF

- Pregnant or nursing

- Significant renal or liver disease