Trial of Bone-marrow Derived Mesenchymal Stromal Cells (MSC) for New Onset Chronic Lung Allograft Dysfunction

NCT ID: NCT02709343

Last Updated: 2023-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-21
• Study Completion Date: 2023-10-25

Brief Summary

This study is designed for lung transplant patients who have developed chronic lung allograft dysfunction (CLAD). Consented patients will receive 4 intravenous doses of allogeneic, bone-marrow-derived MSCs (2*10^6 cells/kg/dose) or matching placebo over a period of 2 weeks with a 12 month follow up.

Detailed Description

This is a phase 2, multi-center, randomized study (n=82, 1:1 MSC:placebo) where consented patients will receive 4 intravenous doses of IMP over a period of 2 weeks. Patients must provide written informed consent and meet the all Inclusion Criteria and none of the Exclusion Criteria to be eligible. Screening procedures include obtaining medical history, current medications, questionnaires, vital signs, Chest Xray, 6 Minute walk test and blood tests. Historical chest CT and full lung function from 12 weeks prior to screening may be used. Bronchoscopy with biopsy must have been performed no more than 6 months prior to screening. A bronchoscopy with bronchoalveolar lavage (BAL) is required, however will not need to be repeated if performed within 14 days prior to the baseline visit. Patients will then receive 4 infusions of MSC/placebo over a period of 2 weeks, with follow up at Week 3,6,10,14,28,41 and week 54.

Conditions

Chronic Lung Allograft Dysfunction (CLAD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Bone-marrow derived MSCs

4 doses of Allogeneic bone-marrow derived MSCs (2x106 cells/kg) given intravenously twice weekly for 2 weeks

Group Type: EXPERIMENTAL

Bone-marrow derived MSCs

Intervention Type: DRUG

Allogeneic ex vivo expanded, bone marrow-derived mesenchymal stromal cells

Placebo

Placebo product manufactured to look like MSCs

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo product visually very similar to mesenchymal stromal cells

Interventions

Bone-marrow derived MSCs

Allogeneic ex vivo expanded, bone marrow-derived mesenchymal stromal cells

Intervention Type: DRUG

Placebo

Placebo product visually very similar to mesenchymal stromal cells

Intervention Type: DRUG

Other Intervention Names

MSC

Eligibility Criteria

Inclusion Criteria

1. Bilateral lung transplant recipients aged ≥ 18 years and at least 6 months post-transplant. Patients with other organs transplanted (eg heart, liver, kidney) or those who have undergone lobar transplantation, or re-transplantation, are potentially eligible.

2. New-onset CLAD (defined as a persistent (3weeks apart) fall in FEV1 of at least 20% from the mean of the two best post-transplant values taken at least 3 weeks apart) in the 12 months prior to the screening visit. Other causes of a fall in FEV1 (acute cellular or humoral rejection, active infection, anastomotic stenosis etc.) must be excluded as per international guidelines.

3. Stable immunosuppression regimen, as assessed by the investigator, in the 8 weeks prior to the screening visit.

4. Available for all specified assessments at the study site through the completion of the study, including the protocol bronchoscopies.

5. Provision of written informed consent.

Exclusion Criteria

1. Any condition that in the opinion of the Investigator may interfere with the safety of the patient, his / her completion of required follow-up visits or evaluation of the study objectives

2. Untreated cellular or humoral rejection

3. Clinically meaningful and untreated viral, bacterial or fungal infection

4. Use of azithromycin or another macrolide antibiotic, if commenced within 8 weeks of the screening visit

5. Intravenous pulsed methylprednisolone, within 4 weeks of the screening visit

6. Use of extracorporeal photopheresis, within 4 weeks of the screening visit

7. Use of total lymphoid irradiation, within 4 weeks of the screening visit

8. Poor functional status not expected to survive 6 months

9. Allergy to beef products

10. Women who are pregnant, breast-feeding or unwilling to use adequate contraception

11. Patients who are currently participating in another interventional clinical trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Isopogen

UNKNOWN

Sponsor Role: collaborator

Cell and Tissue Therapies

UNKNOWN

Sponsor Role: collaborator

The University of Queensland

OTHER

Sponsor Role: lead

Responsible Party

Daniel Chambers

A/Prof Daniel Chambers

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel Chambers, MBBS MD

Role: PRINCIPAL_INVESTIGATOR

University of Queensland & The Prince Charles Hospital

Locations

St Vincents Hospital

Sydney, New South Wales, Australia

The Prince Charles Hospital

Brisbane, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Countries

Australia

Other Identifiers

ASSIST-CLAD

Identifier Type: -

Identifier Source: org_study_id