A First-In-Human Clinical Trial of Lentiviral-mediated CSF2RA Gene Transfer/Pulmonary Macrophage Transplantation Therapy of Hereditary Pulmonary Alveolar Proteinosis
The major goal of this study is to evaluate a new type of cell transplantation therapy for individuals with hereditary PAP, study a new treatment that may be useful for treatment of other diseases, and research mechanisms that drive the development and function of lung macrophages.
∙ Patients must meet all of the following conditions to be eligible for participation in this study:
• 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
• Diffuse ground glass opacification of the lungs visualized on a chest computed tomogram (CT)
• 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
• Able to undergo bone marrow collection by routine clinical aspiration
• 18 years of age or older on the date the Informed consent form (ICF) is signed
• 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.
• 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.
• Signed written informed consent form (ICF)