Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001422819
Ethics application status
Approved
Date submitted
7/07/2021
Date registered
21/10/2021
Date last updated
28/09/2022
Date data sharing statement initially provided
21/10/2021
Date results information initially provided
28/09/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Nebulised media from stem cell cultures for the treatment of chronic obstructive pulmonary disease
Scientific title
A Phase 1 Study to Evaluate the Safety of Nebulised Conditioned Media of Mesenchymal Stromal Cells (MSC) for Treating Chronic Obstructive Pulmonary Disease (COPD)
Secondary ID [1] 304734 0
TGA ID: CT-2021-CTN-02215-1
Universal Trial Number (UTN)
None
Trial acronym
NeMeCo
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Chronic obstructive pulmonary disease (COPD) 322754 0
Condition category
Condition code
Respiratory 320344 320344 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Conditioned media from cultures of allogeneic, bone marrow derived, culture expanded, mesenchymal stromal cells will be produced by CTTWA at RPH. Collection, manufacturing and administration of MSC are performed according to Good Manufacturing Practise (GMP) standards, TGA licenced and audited regularly by the TGA.

Patients will receive one dose (5ml) of nebulised mesenchymal stromal cells conditioned media (MSC-CM) on Day 0, administered by A/Prof Yuben Moodley (Respiratory Physician). Duration of treatment (nebulisation) take about 5 minutes to complete. One of the identified active anti-inflammatory mediators in MSC-CM is soluble TNF receptor 1 (sTNFR1) present at a concentration of ~50 pg/mL. The level of sTNFR1 will first be measured in the batch of MSC-CM used for this study and all participant will receive the same batch of MSC-CM, hence no adjustment of the inhalant is required between participants.
Intervention code [1] 321108 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328197 0
Safety and tolerability of nebulised MSC conditioned media (Neb-MSC-CM) in patients with COPD.

On the Day:
1. Physical examinations
2. Vital signs (Heart Rate, Respiratory Rate, Temperature and Blood pressure using electronic sphygmomanometer and digital thermometer)
3. any adverse events
will be recorded 15 mins prior to the procedure and every 15 minutes for 2hr post-treatment.

Day 2, 7, 14, 30, 60, 90 follow-up:
• Adverse reactions such as cough, wheezing, increased shortness of breath and exacerbations will be recorded
Timepoint [1] 328197 0
On the Day of treatment - every 15 min for 2 hours (15, 30, 45, 60, 75, 90, 105, 120 mins) post-treatment.

Follow-up: Day 2, 7, 14, 30, 60, 90
Secondary outcome [1] 397992 0
Efficacy as indicated by:
- Quality of life measured by the COPD Assessment Tool (CAT) score,
Timepoint [1] 397992 0
Day 0, 2, 7, 14, 30, 60, 90
Secondary outcome [2] 398531 0
Efficacy as indicated by:
- Lung function by spirometry.
Timepoint [2] 398531 0
Day 0, 2, 7, 14, 30, 60, 90
Secondary outcome [3] 398532 0
Efficacy as indicated by:
- Bloods for routine diagnostic tests (e.g. full blood count, renal and liver function, CRP).
Timepoint [3] 398532 0
Day 0, 2, 7, 14, 30, 60, 90
Secondary outcome [4] 398533 0
Efficacy as indicated by:.
• Bloods for research for the measurement of plasma inflammatory and anti-inflammatory molecules (e.g. IL-1ß, IL-6, IL-8 and TNF by cytometric bead array or CRP, TGFß and sTNFR1 by ELISA) and isolation and cryopreservation of PBMC to assess changes in the systemic cell populations and the expression of activation markers by flow cytometry.
These will be assessed as a composite outcome.
Timepoint [4] 398533 0
Day 0, 2, 7, 14, 30, 60, 90

Eligibility
Key inclusion criteria
Patients with clinical features consistent with COPD
- Moderately severe COPD (FEV1 = 40-60% predicted)
- Age > 40 years
- Provision of written informed consent
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inhaled corticosteroids
Malignancy
Immunomodulatory treatment
Diabetes
Severe co-morbidities such as cardiac failure

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
NA
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
Descriptive statistical analysis will be performed to assess changes in immune biomarkers post-treatment in this study.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
19/10/2021
Date of last participant enrolment
Anticipated
27/10/2021
Actual
23/11/2021
Date of last data collection
Anticipated
4/02/2022
Actual
15/02/2022
Sample size
Target
4
Accrual to date
Final
4
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 19941 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 34643 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 309107 0
Other Collaborative groups
Name [1] 309107 0
Institute for Respiratory Health
Country [1] 309107 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Institute for Respiratory Health
Address
L2, Harry Perkins Institute of Medical Research
6 Verdun Street, Nedlands, 6009, WA Australia
Country
Australia
Secondary sponsor category [1] 310056 0
None
Name [1] 310056 0
Address [1] 310056 0
Country [1] 310056 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308975 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 308975 0
Level 2, Education Building,
Fiona Stanley Hospital
14 Barry Marshall Parade
MURDOCH Western Australia 6150
Ethics committee country [1] 308975 0
Australia
Date submitted for ethics approval [1] 308975 0
02/02/2021
Approval date [1] 308975 0
17/02/2021
Ethics approval number [1] 308975 0
RGS4327

Summary
Brief summary
Airways disease such as Chronic Obstructive Pulmonary Disease (COPD) are amongst the top 5 causes of global morbidity and mortality. In Australia, 1 in 10 people above the age of 45 years has COPD and amongst the top 5 most prevalent diseases in Australia. COPD is usually progressive resulting in terminal respiratory failure. Standard therapies include bronchodilators and inhaled corticosteroids. Bronchodilators cause smooth muscle relaxation and may reduce mucus formation. Inhaled corticosteroids reduce eosinophilic inflammation in a cohort of subjects with COPD. Taken together these treatments provide symptomatic relief but do not address the ongoing tissue damage and impaired repair by the disordered immune system.



We have demonstrated for the first time in human subjects that intravenous infusions of human mesenchymal stromal cells (MSCs) reduced systemic inflammation by immune-modulating monocytes and increasing anti-inflammatory T regulatory cells. Furthermore, we have shown that the supernatant or conditioned media in which the MSCs are grown in (MSC-CM) have similar immunosuppressive properties. Notably we demonstrated that when the MSC-CM is nebulised, it retained the anti-inflammatory properties.



We therefore propose to test the safety and potential efficacy of nebulised conditioned media from MSCs (Neb-MSC-CM) in moderate to severe cohorts of COPD patients and those with frequent exacerbations of COPD. We will assess the safety and efficacy by improvements in quality of life, exercise tolerance and lung function and systemic inflammatory markers. The successful completion of this safety study will then allow us to pursue randomised control trials and commercialisation of this product.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112534 0
A/Prof Yuben Moodley
Address 112534 0
Harry Perkins Institute of Medical Research
Fiona Stanley Hospital
5 Robin Warren Dr, Murdoch WA 6150
Country 112534 0
Australia
Phone 112534 0
+61 414383338
Fax 112534 0
Email 112534 0
[email protected]
Contact person for public queries
Name 112535 0
A/Prof Yuben Moodley
Address 112535 0
Harry Perkins Institute of Medical Research
Fiona Stanley Hospital
5 Robin Warren Dr, Murdoch WA 6150
Country 112535 0
Australia
Phone 112535 0
+61 414383338
Fax 112535 0
Email 112535 0
[email protected]
Contact person for scientific queries
Name 112536 0
A/Prof Yuben Moodley
Address 112536 0
Harry Perkins Institute of Medical Research
Fiona Stanley Hospital
5 Robin Warren Dr, Murdoch WA 6150
Country 112536 0
Australia
Phone 112536 0
+61 414383338
Fax 112536 0
Email 112536 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Confidential. Potential IP


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo There was no adverse events recorded for all patie... [More Details]

Documents added automatically
No additional documents have been identified.