Safety and Tolerability Study of Allogeneic Mesenchymal Stem Cell Infusion in Adults With Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: Mesenchymal Stem Cells
Intervention description: A single dose, one time infusion (in the vein) of one of the following doses of human mesenchymal stem cells (hMSCs): 1 x 10^6, 3 x 10^6 or 5 x 10^6 human mesenchymal stem cells per kilogram body weight (hMSCs/kg) during Visit 2. A traditional 3+3 design will be utilized.
Allogeneic mesenchymal stem cells (MSCs) will be derived from bone marrow aspirates from a healthy donor whose serum tests negative for cytomegalovirus (CMV) antibodies. Healthy donors will undergo tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs will be validated for in vitro and in vivo efficacy and potency using the in vivo murine pre-clinical model of cystic fibrosis lung infection and inflammation.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Human Mesenchymal Stem Cells

Summary:

      This study is being done to test if it is safe to give stem cells to adult patients with
      Cystic Fibrosis (CF). The kind of stem cells we are studying are called allogeneic human
      mesenchymal stem cells or MSCs. MSCs are cells in the body that can grow into different types
      of cells and respond to various environmental situations. Allogeneic means the cells come
      from another person (a donor).

      This study is only looking at whether or not it is safe to give the stem cells to adults with
      CF and how the infusion is tolerated. In the future, other studies may be done to see if stem
      cells can be a new therapeutic treatment for CF.

      Stem cells, like other medical products that are intended to treat, cure or prevent disease,
      generally require approval from the U.S. Food and Drug Administration (FDA) before they can
      be marketed. The FDA has not approved any stem cell-based products for usual medical care,
      other than some specific blood forming stem cells for certain indications.
    

Eligibility criteria:

        Cystic Fibrosis (CF) Subject Inclusion Criteria:

          1. Male or female ≥18 years of age

          2. Confirmed diagnosis of CF as evidenced by 1 or more clinical features consistent with
             the CF phenotype and 1 or more of the following criteria:

               1. Sweat chloride equal to or greater than 60 milliequivalents per liter (mEq/L) by
                  quantitative pilocarpine iontophoresis test (QPIT)

               2. 2 well-characterized, disease causing mutations in the cystic fibrosis
                  transmembrane conductance regulator (CFTR) gene

          3. Clinically stable with no significant changes in health status within 2 weeks prior to
             screening.

          4. Forced expiratory volume in the first second (FEV1) ≥ 40% predicted for age based on
             the global lung function initiative equations at the screening visit

          5. Weight ≥ 40 kilograms at the screening visit

          6. Able to perform repeatable, consistent efforts in pulmonary function testing

          7. Written informed consent obtained from the subject.

        CF Subject Exclusion Criteria:

          1. Use of an investigational agent within the 4-week period prior to Visit 1 (Day -42 to
             -10)

          2. Chronic daily (>10 mg) or alternate daily (>20 mg on alternate days) use of systemic
             corticosteroids within the 4 weeks prior to Visit 1 (Day -42 to -10) or initiation of
             any dosage of systemic corticosteroids within 72 hours prior to Visit 2 (Day 1).

          3. Use of hydroxychloroquine or immunosuppressants.

          4. Initiation of a new antibiotic (oral, intravenous, and/or inhaled) that is not part of
             the subject's maintenance regimen for treatment of acute respiratory symptoms within 2
             weeks prior to screening through Visit 2 (Day 1)

          5. Initiation of any new chronic therapy (e.g., Pulmozyme®, hypertonic saline, Kalydeco®,
             Orkambi®, high-dose ibuprofen azithromycin, TOBI®, Cayston®, nebulized colistiin,
             bronchodilators, inhaled corticosteroids, etc.) within 4 weeks prior to screening

          6. Active treatment for non-tuberculous Mycobacteria

          7. History of a sputum culture positive for a Burkholderia cepacia complex organism in
             the previous 12 months.

          8. Current tobacco smoker

          9. Oxygen saturation < 92% on room air at Visit 1 (Day -42 to -10)

         10. History of pulmonary hypertension

         11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the
             upper limit of normal at screening, documented biliary cirrhosis, or portal
             hypertension

         12. Total bilirubin concentration > 1.2 milligram per deciliter (mg/dL) at screening

         13. Creatinine > 1.8 mg/dL at screening

         14. Pregnant, breastfeeding, or unwilling to practice birth control between Visit 2 (Day
             1) and Telephone Call 3 (Day 56) (acceptable forms of contraception: abstinence,
             hormonal birth control, intrauterine device, or barrier method plus a spermicidal
             agent), unless surgically sterilized or postmenopausal

         15. Screening hematology with white blood cell count < 4.5 x 109 cells/liter, hematocrit <
             30%, and platelets < 150 x 109 platelets/liter

         16. History of invasive cancer requiring systemic therapy

         17. History of organ transplantation

         18. Currently listed for lung transplantation or having potential to be listed for lung
             transplantation in the succeeding 12 calendar months from screening

         19. Subject unlikely to complete the study as determined by the Investigator

        Inclusion Criteria for Healthy Volunteer Donors (NOTE: Enrollment for Healthy Volunteers is
        closed):

          1. Male/female age ≥ 18 years to ≤ 40 years

          2. Able to understand and sign consent form (a legally authorized representative will not
             be permitted)

        Inclusion Criteria for CF Donors:

        1. CF subject enrolled in the main study and consented to this optional procedure

        Exclusion Criteria for both Healthy Volunteer (HV) Donors and CF Donors:

          1. Fever or current illness on the day of the cell collection

          2. Evidence of communicable disease

          3. Any significant change in health status within 2 weeks prior to cell collection that
             the Principal Investigator/Sub-Investigator deems relevant to exclude participation

          4. Subject reported history of organ transplantation

          5. Subject reported history of human immunodeficiency virus, hepatitis B or C, or
             syphilis

          6. For HV donors only, subject-reported known history of being diagnosed with cystic
             fibrosis (CF) or being a CF carrier (one copy of CF gene mutation)

          7. Positive screening blood test result for any infectious disease.

          8. For HV donors only, positive test result for CMV or a CF gene mutation.

          9. Pregnant, planning a pregnancy, or breast-feeding at screening