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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02709343




Registration number
NCT02709343
Ethics application status
Date submitted
1/03/2016
Date registered
16/03/2016
Date last updated
4/10/2018

Titles & IDs
Public title
Trial of Bone-marrow Derived Mesenchymal Stromal Cells (MSC) for New Onset Chronic Lung Allograft Dysfunction
Scientific title
Phase 2 Randomised Controlled Trial of Bone-marrow Derived Mesenchymal Stromal Cells (MSC) for New Onset Chronic Lung Allograft Dysfunction (CLAD)
Secondary ID [1] 0 0
ASSIST-CLAD
Universal Trial Number (UTN)
Trial acronym
ASSIST-CLAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lung Allograft Dysfunction (CLAD) 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bone-marrow derived MSCs
Treatment: Drugs - Placebo

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

Placebo Comparator: Placebo - Placebo product manufactured to look like MSCs


Treatment: Drugs: Bone-marrow derived MSCs
Allogeneic ex vivo expanded, bone marrow-derived mesenchymal stromal cells

Treatment: Drugs: Placebo
Placebo product visually very similar to mesenchymal stromal cells

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
From baseline to week 54
Secondary outcome [1] 0 0
Time to fall in FEV1 > 10% - Defined as fall in FEV1 > 10% from the baseline (screening visit) FEV1
Timepoint [1] 0 0
From the baseline (screening) visit
Secondary outcome [2] 0 0
Freedom from Bronchiolitis Obliterans Syndrome (BOS) grade 3 - BOS grade 3 is defined as FEV1 <50% of the best-post-transplant FEV1
Timepoint [2] 0 0
Week 54
Secondary outcome [3] 0 0
All cause mortality
Timepoint [3] 0 0
Week 54
Secondary outcome [4] 0 0
CLAD-specific mortality - Defined as any death felt by the investigator to be at least partially related to CLAD.
Timepoint [4] 0 0
Week 54
Secondary outcome [5] 0 0
Freedom from acute rejection - Acute rejection defined as any biopsy proven episode of acute vascular (A1-A4) or airway (B1R or B2R) rejection.
Timepoint [5] 0 0
From baseline to week 54
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
From baseline to week 14
Secondary outcome [7] 0 0
Freedom from CLAD progression - CLAD progression is defined as fall in FEV1 > 10% from the baseline (screening visit) FEV1 at 12 months.
Timepoint [7] 0 0
From baseline to week 54
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
From baseline to week 54
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
From baseline to week 54
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
From baseline to week 54
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
From baseline to week 54
Secondary outcome [12] 0 0
Inpatient bed-days - This is defined as the aggregate of inpatient bed-days between the screening visit and week 54.
Timepoint [12] 0 0
From baseline to week 54

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
St Vincents Hospital - Sydney
Recruitment hospital [2] 0 0
The Prince Charles Hospital - Brisbane
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
4032 - Brisbane
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
6150 - Murdoch

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Isopogen
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Cell and Tissue Therapies
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02709343
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Daniel Chambers, MBBS MD
Address 0 0
University of Queensland & The Prince Charles Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Daniel Chambers, MBBS MD
Address 0 0
Country 0 0
Phone 0 0
+61 7 3139 4000
Fax 0 0
Email 0 0
daniel.chambers@health.qdl.gov.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02709343