An Open Label, Randomised, Controlled Clinical Trial to Assess the Safety of Endobronchial Administration of Allogeneic Mesenchymal Stromal Cells in Patients with Lung Transplant Chronic Rejection: Study Endosc-Clad

Overview

Sponsor-declared trial summary

Key facts

Sponsor

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

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

22 Feb 2023 → ongoing

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509341-12-00

EudraCT number

2022-000279-38

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To assess the safety of endobronchial administration of allogeneic MSCs in patients with BO.

Secondary objectives 1

1. To assess the efficacy of endobronchial administration of allogeneic MSCs in the BO progression.

Conditions and MedDRA coding

Patients with lung transplant, either unilateral or bilateral and 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.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patients should have signed written informed consent.
2. Adult patients ≥18 years of age at the time of enrolment
3. Patients recipients of a uni or bipulmonary transplant
4. 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 13

1. History of lobar transplantation
2. History of heart-lung transplantation
3. Active infection at the time of inclusion.
4. Active Acute Rejection not treated at the time of inclusion.
5. Oncological history (except cutaneous basal cell or carcinoma in situ)
6. Systemic autoimmune diseases.
7. Active HIV / HBV / HCV infection (confirmed by serology or PCR)
8. Proximal airway stenosis
9. Pregnant women, female subjects planning or willing to get pregnant during the duration of the study will not be able to enroll.
10. 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)
11. Estimated survival less than 3 months.
12. Known hypersensitivity to components used in the production of allogeneic MSCs.
13. Any circumstance that, in the opinion of the investigator, compromises the patient's ability to participate in the clinical trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of early onset (24h) adverse events following MSCs administration: desaturation, hypotension, radiological infiltrates, fever or changes in oxygen therapy requirements.
2. 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).

Secondary endpoints 13

1. Mean changes in FEV1 at 12-month from baseline.
2. Proportion of patients with >10% decrease in FEV1 from baseline.
3. Time to a >10% decrease in FEV1 from baseline.
4. Proportion of patients progressing to grade 3 BO (as defined by a FEV1 below 50% from best value post-transplant).
5. Mean changes in FVC from baseline to 12-month
6. All-cause mortality rate
7. Re-transplant or CLAD-related mortality rate.
8. 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.
9. Incidence of presence of specific antibodies against donor HLA.
10. CLAD progression, as defined by > 10% decline in FEV1 in two consecutive time-points
11. Mean changes in the mMRC Scale at 12-month.
12. Total hospitalization days during 12-month follow-up period.
13. Proportion of patients requiring ambulatory oxygen therapy.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Sponsor organisation

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

Address

Calle De Joaquin Rodrigo 2

City

Majadahonda

Postcode

28222

Country

Spain

Scientific contact point

Organisation

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

Contact name

David Gómez de Antonio

Public contact point

Organisation

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

Contact name

David Gómez de Antonio

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications