Safety and Tolerability Study of Allogeneic Mesenchymal Stem Cell Infusion in Adults With Cystic Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 6 February 2023
• Main ID: NCT02866721
• Date of registration: 07/08/2016
• Prospective Registration: No
• Primary sponsor: University Hospitals Cleveland Medical Center
• Public title: Safety and Tolerability Study of Allogeneic Mesenchymal Stem Cell Infusion in Adults With Cystic Fibrosis CEASE-CF
• Scientific title: A Phase I, Single Center, Open Label, Single Dose, Dose Escalation Study Assessing the Safety and Tolerability of AllogeneiC MEsenchymAl Stem CEll Infusion in Adults With Cystic Fibrosis-CEASE CF
• Date of first enrolment: August 2016
• Target sample size: 14
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02866721
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Erica A. Roesch, MD
• Affiliation: University Hospitals Cleveland Medical Center

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Biological: Mesenchymal Stem Cells

Primary Outcome(s)

Number of Serious Adverse Events and Number of Non-Serious Adverse Events [Time Frame: 1 year]

Forced Expiratory Volume in the First Second (FEV1) % Predicted at Baseline and 30 Minutes, 4 Hours, 24 Hours, 7 Days, 14 Days, 28 Days, 3 Months, 6 Months Post Human Mesenchymal Stem Cell Infusion. [Time Frame: Baseline and 30 minutes, 4 hours, 24 hours, 7 days, 14 days, 28 days, 3 months, 6 months Post Human Mesenchymal Stem Cell Infusion]

Number of Participants With a Dose Limiting Toxicity (DLT), Triggered by Occurrence in the First 24 Hours After Human Mesenchymal Stem Cell (hMSC) Infusion of Grade =3 Infusion-related Allergic Toxicities [Time Frame: 24 hours post infusion]

Number of Pulmonary Exacerbations Requiring Intravenous Antibiotics [Time Frame: 1 year]

Secondary Outcome(s)

Sputum Inflammatory Markers - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Serum Inflammatory Markers - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Serum Inflammatory Markers - Interleukin-1 (IL-1) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Serum Inflammatory Markers - Interleukin-6 (IL-6) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Serum Inflammatory Markers - Interleukin-17 (IL-17) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Serum Inflammatory Markers - Calportectin Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Serum Inflammatory Markers - Myeloperoxidase (MPO) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Sputum Inflammatory Markers - Interleukin-1 (IL-1) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Serum Inflammatory Markers - Tumor Necrosis Factor Alpha (TNF-a) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Sputum Inflammatory Markers - Interleukin-17 (IL-17) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Serum Inflammatory Markers - Interleukin-8 (IL-8) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Sputum Inflammatory Markers - Interleukin-6 (IL-6) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Sputum Inflammatory Markers - Macrophage Inflammatory Protein-3 Alpha (MIP-3a) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Sputum Inflammatory Markers - Interleukin-10 (IL-10) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Sputum Inflammatory Markers - Tumor Necrosis Factor Alpha (TNF-a) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Sputum Inflammatory Markers - Interleukin-8 (IL-8) Measurements at Baseline, Day 7, and Day 28 [Time Frame: Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion]

Secondary ID(s)

Protocol CF-MSC-01

DASENB15A0

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Cystic Fibrosis Foundation

Case Western Reserve University

Results

• Results available: Yes
• Date Posted: 30/01/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02866721