Safety and Efficacy of PMT Therapy of hPAP

Eligibility Criteria

• 1. Male or female with a confirmed diagnosis of hPAP defined as:
• * Homozygous or compound heterozygous CSF2RA mutations - AND -
• * A normal GM-CSF autoantibody test result - AND -
• * An abnormal STAT5-PI test result - OR -
• * An abnormal GM-CSF 50% effective concentration (EC50) test result
• 2. Diffuse ground glass opacification of the lungs visualized on a chest computed tomogram (CT)
• 3. History of prior receipt of WLL therapy or moderate hPAP lung disease severity requiring therapy in the opinion of the Clinical Site Investigator and/or Sponsor
• 4. Able to undergo bone marrow collection by routine clinical aspiration
• 5. 18 years of age or older on the date the Informed consent form (ICF) is signed
• 6. Females who have been post-menopausal for \>2 years or females of child-bearing potential after a confirmed menstrual period using a highly efficient method of contraception (as described in Section 11.4.2) for the period from 3 months prior to the first administration of gene-corrected macrophages until 12 months after the last administration of gene-corrected macrophages. Females of child-bearing potential must have a negative serum pregnancy test at Screening (Visit 1), at bone marrow collection (Visit 2), and immediately before each administration of gene-corrected macrophages (Visits 3, 5, 7), and must not be lactating.
• 7. Males of reproductive potential must agree to use condoms for the period from the 1st administration of gene-corrected macrophages until 12 months after the last dose of gene-corrected macrophages, have a partner who is not of child-bearing potential (i.e. men or females who have been post-menopausal for \>2 years), or have a female partner who is using adequate contraception as described in Section 11.4.2.
• 8. Signed written informed consent form (ICF)
• 1. History of a confirmed diagnosis of any other PAP-causing disease defined as:
• 1. PAP caused by function-altering mutations in CSF2RB, adenosine triphosphate (ATP)-binding cassette subfamily A member 3 (ABCA3), SFTPB, SFTPC, Thyroid Transcription Factor 1 (TTF-1), GATA-binding factor 2 (GATA2), SLC7A7, and methionyl-transfer RNA (tRNA) synthetase (MARS), or other genes demonstrated to cause PAP other than CSF2RA
• 2. PAP associated with an abnormal GM-CSF autoantibody test
• 3. PAP associated with hematologic disorders including but not limited to myelodysplasia, aplastic anemia, leukemia, multiple myeloma, lymphoma
• 4. PAP associated with non-hematologic malignancies
• 5. PAP associated with immune deficiency syndromes
• 6. PAP associated with chronic inflammatory syndromes
• 7. PAP associated with chronic infections including but not limited to human immunodeficiency virus, Mycobacteria tuberculosis or other Mycobacterial species, or other organisms
• 8. PAP associated with inhaled materials including but not limited to inorganic dusts (e.g., silica, titanium, indium, aluminum), organic dusts (e.g., sawdust, fertilizer); or gases/vapors (e.g., cleaning products, paints, and welding-related fumes)
• 2. Pulmonary fibrosis that is clinically significant in the opinion of Clinical Site Investigator and/or Sponsor
• 3. A confirmed (i.e., repeated) positive serum anti-GM-CSF receptor antibody test and/or a confirmed positive anti-lentiviral antibody test at the time of screening and prior to each administration of gene-corrected macrophages
• 4. History of receipt of any investigational agent within 3 months of Study Visit 3
• 5. History of active chronic infection (e.g., HIV, Hepatitis, others) at the time of Screening
• 6. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Study Visit 3, defined as more than 14 drinks/week for females or 21 drinks/week for males (1 drink - 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer, or 1.5 ounces (45 ml) of hard liquor)
• 7. History of medication or illicit drug abuse within 1 year prior to Study Visit 3, including but not limited to cocaine, heroin, or other opioids
• 8. Currently or planning to become pregnant between the Screening visit and Visit 14 and/or currently breast-feeding
• 9. Any other medical, behavioral, or psychiatric condition that would interfere with the completion of Study Visits or assessments in the opinion of the Clinical Site Investigator and/or Sponsor