Study of Autologous Mesenchymal Stem Cells to Treat Idiopathic Pulmonary Fibrosis (CMM/FPI)

• ClinicalTrials.gov Identifier: NCT01919827
• Recruitment Status: Completed
• First Posted: August 9, 2013
• Last Update Posted: May 3, 2018
• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Information provided by (Responsible Party): Clinica Universidad de Navarra, Universidad de Navarra

Tracking Information

• First Submitted Date: August 1, 2013
• First Posted Date: August 9, 2013
• Last Update Posted Date: May 3, 2018
• Study Start Date: March 2013
• Actual Primary Completion Date: May 1, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 6, 2013)

Number of participants with adverse side effects. [ Time Frame: Up to 12 months ]

Number of participants with adverse side effects, and according to the level of severity:

1. Low level: Increase in cough, fever or skin reactions
2. Medium level: Infections not requiring hospital admission, mild alterations of renal or liver function
3. High level: Death or major side effects requiring hospitalization:
   1. Worsening dyspnea with >=10% reduction in forced vital capacity, reduction in arterial pressure oxygen >= 10 mmHg and radiology progression between 3 months separated visits.
   2. Need for hospitalization due to respiratory failure requiring mechanical ventilation, worsening in gases exchange or lung infection.
   3. Carcinogenesis at 12 months after the endobronchial infusion of mesenchymal stem cells.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 27, 2013)

Efficacy of the infusion of mesenchymal stem cells in stopping the fall in pulmonary function in patients with mild to moderate IPF [ Time Frame: Up to 12 months ]

Measures of efficacy:

1. Fall in forced vital capacity as a continuous variable
2. Progression of the disease defined by: Death, need for transplantation or deterioration in pulmonary function defined by fall in forced vital capacity (FVC) > 10% or in lung diffusion capacity (DLCO) > 15%.

Original Secondary Outcome Measures (submitted: August 6, 2013)

Assess the efficacy of the infusion of mesenchymal stem cells in stopping the fall in pulmonary function in patients with mild to moderate IPF [ Time Frame: Up to 12 months ]

Measures of efficacy:

1. Fall in forced vital capacity as a continuous variable
2. Progression of the disease defined by: Death, need for transplantation or deterioration in pulmonary function defined by fall in forced vital capacity (FVC) > 10% or in lung diffusion capacity (DLCO) > 15%.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Autologous Mesenchymal Stem Cells to Treat Idiopathic Pulmonary Fibrosis
• Official Title: Treatment of Idiopathic Pulmonary Fibrosis With Bone Marrow Derived Mesenchymal Stem Cells

Brief Summary

Clinical Trial Phase I, open, multicentric, non randomized, study with escalating doses, to evaluate the safety and feasibility of treatment with mesenchymal stem cells in patients with diagnosis of idiopathic pulmonary fibrosis.

Primary endpoint: The aim is to evaluate the safety and feasibility of the endobronchial administration of mesenchymal autolog stem cells derived from bone marrow (BM-MSC)in patients with mild-to-moderate idiopathic pulmonary fibrosis.

Secondary endpoint:Assess the possible effect of the infusion of BM-MSC in stopping the fall of pulmonary function in patients with mild-to-moderate idiopathic pulmonary fibrosis.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Idiopathic Pulmonary Fibrosis

Intervention

• Biological: Endobronchial infusion of adult mesenchymal stem cells
• Biological: Autologous mesenchymal stem cells derived from bone marrow

Study Arms

Experimental: MSC endobronchial infusion

Interventions:

• Biological: Endobronchial infusion of adult mesenchymal stem cells
• Biological: Autologous mesenchymal stem cells derived from bone marrow

• Publications *: Campo A, Gonzalez-Ruiz JM, Andreu E, Alcaide AB, Ocon MM, De-Torres J, Pueyo J, Cordovilla R, Villaron E, Sanchez-Guijo F, Barrueco M, Nunez-Cordoba J, Prosper F, Zulueta JJ. Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis: a phase I trial. ERJ Open Res. 2021 Jun 28;7(2):00773-2020. doi: 10.1183/23120541.00773-2020. eCollection 2021 Apr.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 5, 2017): 17
• Original Estimated Enrollment (submitted: August 6, 2013): 18
• Actual Study Completion Date: May 1, 2018
• Actual Primary Completion Date: May 1, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

INCLUSION CRITERIA:

1. Capacity for signing informing consent and express the willing to fulfill all the requirements of the study protocol during the study.
2. The patients should be, in the researcher opinion, capable to fulfill all the requirements of the trial.
3. Male or female patients, 30 to 80 years old, inclusive.

4. Diagnosis of idiopathic pulmonary fibrosis according to the following criteria, based on the ATS/ERS Guidelines:

   1. Definite or probable usual interstitial pneumonia confirmed by surgical lung biopsy.
   2. In the absence of surgical lung biopsy, all the following:

   i. High resolution CT (HRCT) showing definite findings for idiopathic pulmonary fibrosis (FPI): bibasal reticular opacities with minimal ground glass opacities.

   ii. Absence of other known causes of FPI including toxicity from drugs, environmental exposure or connective tissue diseases.

   iii. Pulmonary function tests showing ventilatory restrictive pattern and/or impaired gas exchange (FVC and/or DLCO <90% of predicted)

5. FVC ≥ 50% of predicted value with ratio of FEV1 to FVC ≥ 0.70.
6. DLco (corrected for hemoglobin) ≥ 35% predicted value.
7. Capability of performing a 6 minutes walk test at the time of inclusion.

EXCLUSION CRITERIA:

Any of the following:

1. Current pregnancy or lactation.
2. Findings that are diagnostic of an interstitial pneumonia or restrictive respiratory disease condition other than UIP.
3. Obstructive pulmonary disease defined by FEV1/FVC < 0,7 or significant emphysema on HRCT.
4. Evidence of sustained improvement in FPI defined by improvement of respiratory function tests before inclusion, observed in >=2 test over the year prior to inclusion.
5. Active or recent respiratory infection (less than 60 days before inclusion) or history of frequent exacerbations of IPF from an infectious cause (more than 2/year over the last 2 years)
6. Hospitalization in the 60 days prior to inclusion due to acute exacerbation of IPF.
7. Chronic cardiac failure (functional class NYHA III/IV) or left ventricular ejection fraction < 25%.
8. Chronically receiving corticosteroid more than 10 mg of prednisone or equivalent, immunosuppressors or antifibrotic agents, including pirfenidone, D-penicillamine, colchicine, ciclosporin A, TNF-alpha antagonists, imatinib, IFN-gamma, azathioprine, cyclophosphamide, within the 30 days prior to inclusion.
9. The patient requires hemodialysis, peritoneal dialysis or hemofiltration.
10. History of malignancy, with the exception of skin squamous or basocellular carcinoma or cervix in situ carcinoma treated successfully.
11. History of ethanol abuse within the year prior to inclusion
12. The patient is participating in a clinical trial which includes other drugs or research products within the 28 days prior to baseline assessment.
13. Comorbidities limiting life expectancy to less than 12 months from the baseline assessment.
14. Medical or psychiatric condition serious or active which might interfere with the treatment of study, assessment or protocol fulfillment.
15. Positive test for HBsAg, HCV antibody, syphilis screening essays, or HIV antibody at screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT01919827
• Other Study ID Numbers: CMM/FPI
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
• Original Responsible Party: Same as current
• Current Study Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Clinica Universidad de Navarra, Universidad de Navarra
• Verification Date: May 2018