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

Chronic Lung Allograft Dysfunction (CLAD) Clinical Trial

— ASSIST-CLAD  

Official title:

Phase 2 Randomised Controlled Trial of Bone-marrow Derived Mesenchymal Stromal Cells (MSC) for New Onset Chronic Lung Allograft Dysfunction (CLAD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02709343
• Other study ID #: ASSIST-CLAD
• Status: Completed
• Phase: Phase 2
• Start date: April 21, 2017
• Est. completion date: October 25, 2023

Study information

• Verified date: December 2023
• Source: The University of Queensland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: October 25, 2023
• Est. primary completion date: September 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lung Allograft Dysfunction (CLAD)

Intervention

Drug:
• Bone-marrow derived MSCs
Allogeneic ex vivo expanded, bone marrow-derived mesenchymal stromal cells
• Placebo
Placebo product visually very similar to mesenchymal stromal cells

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	The Prince Charles Hospital	Brisbane	Queensland
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	St Vincents Hospital	Sydney	New South Wales

Sponsors (3)

Lead Sponsor	Collaborator
The University of Queensland	Cell and Tissue Therapies, Isopogen

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	Progression-free survival is a composite end-point of freedom from CLAD progression or death from any-cause. CLAD progression is defined as fall in FEV1 > 10% from the baseline (screening visit) FEV1 to the 12 month (week 54) visit.	From baseline to week 54
Secondary	Time to fall in FEV1 > 10%	Defined as fall in FEV1 > 10% from the baseline (screening visit) FEV1	From the baseline (screening) visit
Secondary	Freedom from Bronchiolitis Obliterans Syndrome (BOS) grade 3	BOS grade 3 is defined as FEV1 <50% of the best-post-transplant FEV1	Week 54
Secondary	All cause mortality		Week 54
Secondary	CLAD-specific mortality	Defined as any death felt by the investigator to be at least partially related to CLAD.	Week 54
Secondary	Freedom from acute rejection	Acute rejection defined as any biopsy proven episode of acute vascular (A1-A4) or airway (B1R or B2R) rejection.	From baseline to week 54
Secondary	Freedom from the development of new donor specific anti-HLA antibodies	An anti-HLA antibody (any mean fluorescent intensity level) with specificity for a donor HLA type at 3 months which was not present prior to IMP treatment	From baseline to week 14
Secondary	Freedom from CLAD progression	CLAD progression is defined as fall in FEV1 > 10% from the baseline (screening visit) FEV1 at 12 months.	From baseline to week 54
Secondary	Rate of FEV1 decline	Rate of FEV1 decline is defined as the slope of the regression line for FEV1 between the screening visit and week 54	From baseline to week 54
Secondary	Rate of FVC decline	Rate of FVC decline is defined as the slope of the regression line for FVC between the screening visit and week 54	From baseline to week 54
Secondary	Change in 6-minute walk distance (6MWD)	Change in 6MWD is defined as the difference between the 6MWD at screening and the week 54 visit. Patients who have died by week 54 will receive a 6MWD of 0.	From baseline to week 54
Secondary	Change in St George's Respiratory Questionnaire (SGRQ) Score	Change in SGRQ is defined as the difference between the total SGRQ at screening and the week 54 visit. Patients who have died by week 54 will receive a SGRQ of 0.	From baseline to week 54
Secondary	Inpatient bed-days	This is defined as the aggregate of inpatient bed-days between the screening visit and week 54.	From baseline to week 54