Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000840987
Ethics application status
Approved
Date submitted
10/07/2020
Date registered
26/08/2020
Date last updated
26/08/2020
Date data sharing statement initially provided
26/08/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Mesenchymal stromal cell (MSC) therapy for COVID-19 pneumonia
Scientific title
Phase I trial on safety and tolerability of bone-marrow derived mesenchymal stromal cells (MSC) for deteriorating COVID-19 pneumonia
Secondary ID [1] 301718 0
Royal Perth Hospital (15261)
Protocol Number: RGS0000003982
Secondary ID [2] 301719 0
CTN Application ID: CT-2020-CTN-01580-1 v1
Universal Trial Number (UTN)
U1111-1254-9427
Trial acronym
MSCCOVIDP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 pneumonia 318178 0
Condition category
Condition code
Respiratory 316191 316191 0 0
Other respiratory disorders / diseases
Infection 316192 316192 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Allogeneic, bone marrow derived, culture expanded mesenchymal stromal cells
Dose: 2 x 10^6 cells/kg patient weight
Duration: day 0 and day 3
Mode: intravenous administration
Administered by: respiratory physcian
Intervention recorded in patient charts, on product infusion records and in product tracking records.
Intervention code [1] 318022 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324373 0
Safety and tolerability of MSC infusions by adverse events recorded including:
Infusion toxicity related to MSC determined by clinical assessment. Clinical assessment includes monitoring of vital signs and physical examination
Hypersensitivity reactions determined by clinical assessment
Desaturation of oxygen level as measured by pulse oximeter, during or in the 4 hours after MSC infusion (defined by a drop in O2 saturation of 2% or a change to supplemental oxygen therapy)
Hypoxia requiring intubation within 2 hours of MSC infusion by clinical assessment
Timepoint [1] 324373 0
Day 0 and day 3 post infusion of MSC.
Primary outcome [2] 324594 0
Rate of secondary infection following study intervention as assessed by microbial and infectious disease testing of blood and other samples and other assessments as indicated, and obtained from the clinical case record review.
Timepoint [2] 324594 0
Within 30 days post infusion
Primary outcome [3] 324595 0
Safety by routine assessments and standard of care including:
Concomitant medications, therapies and procedures obtained from patient source notes and clinical care records
Physical examination
Full blood count including white cell differential and platelets, reticulocyte count
Biochemistry- urea, electrolytes, creatinine, liver function, lactate dehydrogenase, CRP, d-dimer
Timepoint [3] 324595 0
Day 3, 7, 14, 30 and 90 following study intervention
Secondary outcome [1] 384488 0
Requirement for oxygen therapy to maintain SaO2>92% over time from patient clinical care records.
Timepoint [1] 384488 0
Day 3, 7, 14 and 30 post intervention administration
Secondary outcome [2] 385132 0
Requirement for ICU admission, requirement for mechanical ventilation and duration of ICU admission among ICU eligible patients from patient clinical care records.
Timepoint [2] 385132 0
Day 30 post intervention administration
Secondary outcome [3] 385133 0
Mechanical ventilation free days from patient clinical care records
Timepoint [3] 385133 0
Day 30 post intervention administration
Secondary outcome [4] 385134 0
Hospital length of stay from patient medical records.
Timepoint [4] 385134 0
Day 30 post intervention
Secondary outcome [5] 385135 0
Clinical status from patient clinical care records including COVID status and lung clearance
Timepoint [5] 385135 0
Day 3, 7, 30 and day 90 post intervention administration
Secondary outcome [6] 385136 0
Incidence of ARDS by standard PaO2/FiO2 and assessed by peripheral oximetry or arterial blood gases if clinically indicated.
Timepoint [6] 385136 0
Day 30 post intervention administration
Secondary outcome [7] 385137 0
Incidence of secondary cardiac damage as a composite and measured by AMI rate, arrhythmia rate and peak troponin obtained by ECG and by serum assay, respectively.
Timepoint [7] 385137 0
Day 90 post intervention administration
Secondary outcome [8] 385138 0
Treatment effect on inflammatory markers from blood samples, including serum analysis for C-reactive protein (CRP), interleukin (IL)-6, IL-10, tumour necrosis factor (TNF)a and extracellular vesicles.
Timepoint [8] 385138 0
Day 0 prior to intervention administration and day 3, 7 and 14 post intervention administration.
Secondary outcome [9] 385318 0
Radiological status as determined by CT scan/chest x ray
Timepoint [9] 385318 0
Day 3, 7 and 30 post intervention administration

Eligibility
Key inclusion criteria
Confirmed bi-lateral pneumonia on chest X-ray
Confirmed COVID-19 infection
Worsening hypoxia with an increasing oxygen requirement by 2L/min (Hudson mask or nasal prongs) to maintain SaO2>92%, measured on 2 occasions over >2 hours or requiring more than 4L/min to maintain SaO2>92% with no history suggestive of chronic hypoxia.
Planned for active treatment with goals of care category A, B or C, including those not eligible for ICU transfer.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Life expectancy < 48 hours or GOPC D (palliation only).
Any condition that in the opinion of the investigator may interfere with the safety of the patient or evaluation of study objectives.
Unable to provide consent.
Recent therapy within the last 3 months with immunomodulatory agents including monoclonal antibodies and anti-neoplastics.
Age <18 years
Enrolled in another interventional trial.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistical analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
5/05/2020
Date of last participant enrolment
Anticipated
30/12/2020
Actual
Date of last data collection
Anticipated
31/03/2021
Actual
Sample size
Target
10
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 17039 0
Royal Perth Hospital - Perth
Recruitment hospital [2] 17040 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 30708 0
6000 - Perth
Recruitment postcode(s) [2] 30709 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 306156 0
Hospital
Name [1] 306156 0
Royal Perth Hospital
Country [1] 306156 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital Cell & Tissue Therapies WA
Address
Cell & Tissue Therapies WA
Royal Perth Hospital
Wellington Street
Perth WA 6000
Country
Australia
Secondary sponsor category [1] 306627 0
None
Name [1] 306627 0
Address [1] 306627 0
Country [1] 306627 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306372 0
Royal Perth Hospital (RPH) Human Ethics Committee
Ethics committee address [1] 306372 0
Royal Perth Hospital
Wellington Street
Perth WA 6000
Ethics committee country [1] 306372 0
Australia
Date submitted for ethics approval [1] 306372 0
03/04/2020
Approval date [1] 306372 0
29/04/2020
Ethics approval number [1] 306372 0
RGS0000003982

Summary
Brief summary
The cytokine storm, resulting from the extreme immune response to COVID-19 virus, has been identified as the key event that leads to the acute respiratory distress and multiple organ damage, eventually leading to death in COVID-19 infection. The cell therapy, mesenchymal stromal cells (MSC), secrete anti-inflammatory factors that can prevent the cytokine storm. The first published report of 7 patients with severe COVID-19 pneumonia showed that MSC therapy was able to change the inflammatory status of severely ill patients and significantly improve pulmonary function. The small study demonstrated that MSC therapy was safe and effective in severe COVID-19 pneumonia.

Our centre manufactures an allogeneic MSC product, under licence from Isopogen Pty Ltd, that is cryopreserved for off-the-shelf use. No donor matching is required and the MSC have natural immunity to COVID-19.

The objective of this study is to identify and treat deteriorating COVID-19 patients with MSC therapy to attenuate the cytokine storm response to the COVID-19 virus and thus prevent acute respiratory distress and multi organ damage, improving chance of survival.

This is an open label trial, planned to recruit and consent 10 high risk patients on admission. Patients will receive MSC infusions if they are COVID-19 positive and have increasing oxygen requirements to maintain O2 sat of >92%. The primary study endpoint is safety, with secondary endpoints of clinical parameter assessment, including oxygen requirements, ventilatory support, ICU admission, length of stay, survival and the effect of treatment on inflammatory markers.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103650 0
Dr Ben Carnley
Address 103650 0
Cell & Tissue Therapies WA
Royal Perth Hospital
Wellington Street
Perth WA 6000
Country 103650 0
Australia
Phone 103650 0
+61 8 92242405
Fax 103650 0
+61 8 92241420
Email 103650 0
[email protected]
Contact person for public queries
Name 103651 0
Marian Sturm
Address 103651 0
Cell & Tissue Therapies WA
Royal Perth Hospital
Wellington Street
Perth WA 6000
Country 103651 0
Australia
Phone 103651 0
+61 8 92241987
Fax 103651 0
+61 8 92241420
Email 103651 0
[email protected]
Contact person for scientific queries
Name 103652 0
Marian Sturm
Address 103652 0
Cell & Tissue Therapies WA
Royal Perth Hospital
Wellington Street
Perth WA 6000
Country 103652 0
Australia
Phone 103652 0
+61 8 92241987
Fax 103652 0
+61 8 92241420
Email 103652 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
Data will be provided in publication of trial outcome. This will exclude raw and individual participant data.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.