Safety and Efficacy of PMT Therapy of hPAP

NCT05761899 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: 2022-0424R33HL156888
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hereditary Pulmonary Alveolar Proteinosis

Keywords

Pulmonary Alveolar Proteinosis; Pulmonary Macrophage Transplantation

Outcome Measures

Primary Outcomes (1)

• Number of patients with adverse events (AEs)

  Number of patients with a CTCAE grade 3 or 4 AE in clinical history findings, physical exam findings, vital signs, clinical laboratory values, pulmonary function data, cardiac function, chest x-ray, chest CT at any time during the study period after initiation of PMT Therapy

  Pre- and Post-PMT Therapy for 15 years

Secondary Outcomes (25)

• Tolerability of Pulmonary Macrophage Transplantation (PMT) Therapy

  For 2 days prior to PMT, immediately upon completion of PMT, and daily for 5 days following each PMT procedure.

• Number of patients with an increase in anti-GM-CSF receptor alpha antibodies

  Pre- and Post-PMT Therapy for 15 years

• Number of patients with evidence of clonal lentiviral positive cell expansion

  Pre- and Post-PMT Therapy for 15 years

• Number of patients with lentiviral vector insertion site analysis indicative of clonal dominance or leukemia

  Pre- and Post-PMT Therapy for 15 years

• Number of patients with increased biomarkers of inflammation in bronchoalveolar lavage (BAL) fluid or serum

  Pre- and Post-PMT Therapy for 15 years

Other Outcomes (3)

• Percentage of bronchoalveolar lavage cells that respond to GM-CSF stimulation

  16 months

• Cell population dynamics of transplanted macrophages via RNA sequencing t-distributed stochastic neighborhood embedding analysis (t-SNE)

  16 months

• Transcriptional regulation of alveolar macrophage specification via an assay for transposable-accessible chromatin with sequencing

  16 months

Study Arms (1)

Gene-Corrected Macrophages

EXPERIMENTAL

Autologous bone marrow CD34+ cell-derived, CSF2RA lentiviral vector-transduced macrophages (CSF2RA gene-corrected macrophages) by bronchoscopic instillation into individual lung segments.

Combination Product: Gene-Corrected Macrophages administered by bronchoscopic instillation

Interventions

Gene-Corrected Macrophages administered by bronchoscopic instillation COMBINATION_PRODUCT

This study will evaluate administration of autologous bone marrow CD34+ cell-derived, CSF2RA lentiviral vector-transduced macrophages (CSF2RA gene-corrected macrophages) by bronchoscopic instillation into individual lung segments on three occasions at 2-month intervals in patients with hPAP. The target (maximum) number of cells to be administered is 778 million gene-corrected macrophages per 70 kg patient, which is equal to 11.1 million cells/kg of ideal body weight.

Gene-Corrected Macrophages

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• Patients who meet any of the following conditions will not be eligible for participation in this study:
• History of a confirmed diagnosis of any other PAP-causing disease defined as:
• 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
• PAP associated with an abnormal GM-CSF autoantibody test
• PAP associated with hematologic disorders including but not limited to myelodysplasia, aplastic anemia, leukemia, multiple myeloma, lymphoma
• PAP associated with non-hematologic malignancies
• PAP associated with immune deficiency syndromes
• PAP associated with chronic inflammatory syndromes
• PAP associated with chronic infections including but not limited to human immunodeficiency virus, Mycobacteria tuberculosis or other Mycobacterial species, or other organisms
• 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)
• Pulmonary fibrosis that is clinically significant in the opinion of Clinical Site Investigator and/or Sponsor
• 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
• History of receipt of any investigational agent within 3 months of Study Visit 3
• History of active chronic infection (e.g., HIV, Hepatitis, others) at the time of Screening
• 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)

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• University of South Florida: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

MeSH Terms

Conditions

Pulmonary Alveolar Proteinosis

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Study Officials

• Christopher Towe, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bruce Trapnell

CONTACT

513-636-6361; Bruce.Trapnell@cchmc.org

Brenna Carey

CONTACT

513-636-8916; Brenna.Carey@cchmc.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: March 9, 2023
• Study Start: June 26, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2038
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)