Allogeneic bone marrow-derived mesenchymal adult stromal cells, ex-vivo expanded for Chronic lung allograft dysfunction (CLAD) | Bronchiolitis obliterans syndrome (BOS) in lung transplant recipients

Inclusion criteria

• {"criterion_text":"- Patients should have signed written informed consent."}
• {"criterion_text":"- Adult patients ≥18 years of age at the time of enrolment"}
• {"criterion_text":"- Patients recipients of a uni or bipulmonary transplant"}
• {"criterion_text":"- An established diagnosis of BOS ≧ 0p (FEV1≤90% and / or FEF 25-75% ≤ of the baseline value with no other justifying cause) in the last 6 months."}

Exclusion criteria

• {"criterion_text":"- History of lobar transplantation"}
• {"criterion_text":"- Performance status 3 or 4 (confined to bed or chair for more than 50% of waking hours, able only to perform some self-care activities)"}
• {"criterion_text":"- Estimated survival less than 3 months."}
• {"criterion_text":"- Known hypersensitivity to components used in the production of allogeneic MSCs."}
• {"criterion_text":"- Any circumstance that, in the opinion of the investigator, compromises the patient's ability to participate in the clinical trial."}
• {"criterion_text":"- History of heart-lung transplantation"}
• {"criterion_text":"- Active infection at the time of inclusion."}
• {"criterion_text":"- Active Acute Rejection not treated at the time of inclusion."}
• {"criterion_text":"- Oncological history (except cutaneous basal cell or carcinoma in situ)"}
• {"criterion_text":"- Systemic autoimmune diseases."}
• {"criterion_text":"- Active HIV / HBV / HCV infection (confirmed by serology or PCR)"}
• {"criterion_text":"- Proximal airway stenosis"}
• {"criterion_text":"- Pregnant women, female subjects planning or willing to get pregnant during the duration of the study will not be able to enroll."}

Primary endpoints

• {"endpoint_text":"- Incidence of early onset (24h) adverse events following MSCs administration: desaturation, hypotension, radiological infiltrates, fever or changes in oxygen therapy requirements.","definition_or_measurement_approach":"Incidence measured within 24 hours after MSC administration; events enumerated as desaturation, hypotension, radiological infiltrates, fever or changes in oxygen therapy requirements."}
• {"endpoint_text":"- Incidence of adverse events of special interest since randomization: lower respiratory tract infections, acute rejection (as defined by the presence of A1-A4 o B1R, B2R in biopsy), BO worsening (as measured by >10% decline in FEV1 from baseline).","definition_or_measurement_approach":"Incidence measured from randomization; acute rejection defined by presence of A1-A4 or B1R/B2R in biopsy; BO worsening defined as >10% decline in FEV1 from baseline."}

Secondary endpoints

• {"endpoint_text":"- Mean changes in FEV1 at 12-month from baseline.","definition_or_measurement_approach":"Mean change in FEV1 measured at 12 months versus baseline."}
• {"endpoint_text":"- Proportion of patients with >10% decrease in FEV1 from baseline.","definition_or_measurement_approach":"Proportion of patients experiencing >10% decrease in FEV1 from baseline."}
• {"endpoint_text":"- Time to a >10% decrease in FEV1 from baseline.","definition_or_measurement_approach":"Time-to-event analysis: time from baseline to first observation of >10% decline in FEV1."}
• {"endpoint_text":"- Proportion of patients progressing to grade 3 BO (as defined by a FEV1 below 50% from best value post-transplant).","definition_or_measurement_approach":"Proportion progressing to grade 3 BO defined as FEV1 <50% of best post-transplant value."}
• {"endpoint_text":"- Mean changes in FVC from baseline to 12-month","definition_or_measurement_approach":"Mean change in FVC measured at 12 months versus baseline."}
• {"endpoint_text":"- All-cause mortality rate","definition_or_measurement_approach":"All-cause mortality measured over follow-up period (12 months)."}
• {"endpoint_text":"- Re-transplant or CLAD-related mortality rate.","definition_or_measurement_approach":"Rate of death due to re-transplantation or CLAD-related causes during follow-up."}
• {"endpoint_text":"- Rate of acute rejection (as defined by the presence of A1-A4 o B1R, B2R in biopsy) at any time during the 12-month follow up period.","definition_or_measurement_approach":"Incidence rate of biopsy-defined acute rejection (A1-A4 or B1R/B2R) during 12-month follow-up."}
• {"endpoint_text":"- Incidence of presence of specific antibodies against donor HLA.","definition_or_measurement_approach":"Incidence of donor-specific anti-HLA antibodies detected."}
• {"endpoint_text":"- CLAD progression, as defined by > 10% decline in FEV1 in two consecutive time-points","definition_or_measurement_approach":"Progression defined as >10% decline in FEV1 on two consecutive measurements."}
• {"endpoint_text":"- Mean changes in the mMRC Scale at 12-month.","definition_or_measurement_approach":"Mean change in mMRC dyspnea scale at 12 months versus baseline."}
• {"endpoint_text":"- Total hospitalization days during 12-month follow-up period.","definition_or_measurement_approach":"Sum of hospitalisation days per patient over 12-month follow-up."}
• {"endpoint_text":"- Proportion of patients requiring ambulatory oxygen therapy.","definition_or_measurement_approach":"Proportion of patients who require ambulatory oxygen therapy during follow-up."}

Spain

Earliest CTIS Part Ii Submission Date

06-11-2024

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

443

Number Of Sites

1

Number Of Participants

12

Primary sponsor

Full Name

Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain