Allogeneic MSC Treatment for Pulmonary Emphysema

NCT04918706 | Unknown Phase 2 DMC

• 1 other identifier: HEP study
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Pulmonary emphysema is a component of Chronic Obstructive Pulmonary Disease (COPD) characterized by chronic inflammation with neutrophils and monocytes mediating the tissue destruction under the regulation of various types of lymphocytes. Bone marrow-derived mesenchymal stromal cells have potential to halt the progressive inflammatory response as indicated by the investigator's pilot study (CCMO NL28562.000.09) . Objective: To determine whether patients with emphysema develop anti-inflammatory and tissue repair responses by treatment with allogeneic bone marrow-derived mesenchymal stromal cells (MSC) from healthy donors. Study design: an explorative double-blind, placebo-controlled randomized (2:1) trial in 30 patients with moderate to severe emphysema who are scheduled for two separate sessions for surgical lung volume reduction (LVRS). The study treatment is intravenous allogeneic MSC or placebo treatment in between the first and second surgical session. Randomisation will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to receive placebo) at week 4 and 3 before the second LVRS, and will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to placebo) at week 12 and 11 before the second LVRS. Main study parameters/endpoints: the study has a co-primary endpoint. First, the difference in expression of CD31 on cells per micrometer alveolar septae present in lung tissue harvested at the second LVRS from patients who received MSC at 3 and 4 weeks prior to LVRS2 or placebo. Second, the difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following LVRS2.

Conditions

Pulmonary Emphysema; Mesenchymal Stromal Cells

Keywords

Allogeneic mesenchymal stromal cells; Pulmonary Emphysema; Long volume reduction surgery; Inflammation

Outcome Measures

Primary Outcomes (2)

• Difference in expression of CD31

  The difference in expression of CD31 on cells per micrometer alveolar septae present in lung tissue harvested at the second LVRS from patients who received MSC at 3 and 4 weeks prior to LVRS2 or placebo

  Within one year after the last study patient had its second lung surgical procedure

• The difference between MSC and placebo treatment in change in CO diffusion capacity

  The difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following LVRS2

  1 year after the last CO diffusion measurement

Secondary Outcomes (5)

• The differences in expression of Surfactant Protein-C expression by alveolar type II cells in lung tissue obtained from study patients treated with placebo or MSC.

  Within one year after the last study patient had its second lung surgical procedure

• The difference in immunostaining of various leukocytes in resected lung tissue, including T lymphocytes, B lymphocytes, macrophages and neutrophils obtained from study patients treated with placebo or MSC.

  Within one year after the last study patient had its second lung surgical procedure

• The difference in shear stress responses, expressed as % elongation of 100 cells, of isolated pMVECs ex vivo obtained from study patients treated with placebo or MSC.

  Within one year after the last study patient had its second lung surgical procedure

• The difference in endothelial microparticles concentration and concentration of immunological markers in blood samples from study patients treated with placebo or MSC.

  Within one year after the last study patient had its second lung surgical procedure

• The correlation between arterial pO2 or gas transfer value TLCO (measured as standard of care) and the outcome of the primary objective of the study for patients treated with MSC or placebo.

  at 12 weeks, as well as after 6 and 12 months, after discharge of admission for LVRS2

Other Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events

  3 years after last LVRS2

• Possible confounder smoking

  4 years afters last LVRS2

• Possible confounder emphysema severity

  4 years afters last LVRS 2

Study Arms (4)

MSC week 4 and 3 before LVRS2

EXPERIMENTAL

Allogeneic mesenchymal Stromal cells: 2 x 10\^6/kg body weight MSC in a range of 1.5 x 10\^6 MSC/ kg to 2.5 x 10\^6 MSC/kg (at a maximum of 200 x10\^6 MSC per study participant) with 5% DMSO iv

Genetic: Allogeneic MSC

Placebo week 4 and 3 before LVRS2

PLACEBO COMPARATOR

Placebo: consisting of a 5% DMSO-solution in isotonic solution

Drug: Placebo

MSC week 12 and 11 before LVRS2

EXPERIMENTAL

Allogeneic mesenchymal Stromal cells: 2 x 10\^6/kg body weight MSC in a range of 1.5 x 10\^6 MSC/ kg to 2.5 x 10\^6 MSC/kg (at a maximum of 200 x10\^6 MSC per study participant) with 5% DMSO iv

Genetic: Allogeneic MSC

Placebo week 12 and 11 before LVRS2

PLACEBO COMPARATOR

Placebo: consisting of a 5% DMSO-solution in isotonic solution

Drug: Placebo

Interventions

Allogeneic MSC GENETIC

These MSCs will originate from bone marrow that will be aspirated from healthy volunteer donors screened by a trained physician of the center for stem cell therapy of LUMC

MSC week 12 and 11 before LVRS2; MSC week 4 and 3 before LVRS2

Placebo DRUG

The placebo will be an equivalent volume NaCl 0,9% and DMSO 5%

Placebo week 12 and 11 before LVRS2; Placebo week 4 and 3 before LVRS2

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial;
• Scheduled for lung volume reduction surgery for emphysema as determined by a referring chest physician;
• Pre-bronchodilator measured FEV1 between 20% and 45% predicted; TLCO between 30% and 45% pred.; RV/TLC ≥ 50%;
• Patients in a stable clinical condition.

You may not qualify if:

• Significant cardiac failure;
• Active smoking, or \< 6 months smoking cessation;
• Failure to complete pulmonary rehab program before randomization
• Women of child bearing potential;
• Any cancer treated in the previous 5 years;
• Women of child-bearing potential not using adequate contraception;
• Any other condition of the patient that the clinical investigator deemed harmful for study participation.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Erasmus Medical Center: collaborator
• Amsterdam UMC, location VUmc: collaborator

Study Sites (1)

Department of Pulmonology, Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

RECRUITING

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MeSH Terms

Conditions

Pulmonary Emphysema; Inflammation

Condition Hierarchy (Ancestors)

Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jan Stolk, MD

CONTACT

+31715262950; jstolk@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Model Details: Randomisation (2:1) will allocate 30 patients to two treatment groups. The first group will receive either 2 x 10\^6/kg body weight MSC in a range of 1.5 x 10\^6 MSC/ kg to 2.5 x 10\^6 MSC/kg (at a maximum of 200 x10\^6 MSC per study participant) with 5% DMSO iv or placebo (consisting of a 5% DMSO-solution in isotonic solution) at week 4 and 3 before the second LVRS. The second group will receive either the same dose of 2 x 10\^6/kg body weight MSC iv or placebo at week 12 and 11 before the second LVRS.

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: June 9, 2021
• Study Start: June 25, 2019
• Primary Completion: September 1, 2021
• Study Completion: June 1, 2022
• Last Updated: June 9, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)