Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000612910
Ethics application status
Approved
Date submitted
14/05/2020
Date registered
25/05/2020
Date last updated
12/04/2023
Date data sharing statement initially provided
25/05/2020
Date results information initially provided
12/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The MEND (MEseNchymal coviD-19) Trial: a pilot study to investigate early efficacy of mesenchymal stem cells in adults with respiratory failure due to COVID-19 or another underlying condition.
Updated from
The MEND (MEseNchymal coviD-19) Trial: a pilot study to investigate early efficacy of mesenchymal stem cells in adults with COVID-19  
Reason: Protocol Amendment made after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM
Scientific title
A pilot, open-label, randomised controlled clinical trial to investigate early efficacy of CYP-001 in adults admitted to intensive care with respiratory failure (due to COVID-19 or another underlying condition).
Updated from
A pilot, open-label, randomised controlled clinical trial to investigate early efficacy of CYP-001 in adults admitted to intensive care with COVID-19  
Reason: Protocol Amendment made after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM
Secondary ID [1] 301291 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
The MEND Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 317471 0
ARDS 326207 0
Inserted
 
Reason: Protocol amendment
Updated on 5/05/2022 10:10:15 AM
Condition category
Condition code
Respiratory 315574 315574 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 315577 315577 0 0
Other inflammatory or immune system disorders
Infection 315578 315578 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other- Mesenchymoangioblast-derived mesenchymal stem cells (CYP-001)

Intervention group: Mesenchymoangioblast-derived mesenchymal stem cells (CYP-001) at a dose of 2 million cells/kg (up to a maximum of 200 million cells) by IV infusion on two occasions (Day 1 and Day 3) PLUS standard of care in ICU

Control group: standard of care in ICU

The active agent in CYP-001 is allogeneic mesenchymoangioblast-derived mesenchymal stem cells (MCA-derived MSCs), which are produced using the proprietary Cymerus™ platform technology. Cymerus™ refers to the process of generating cell-based products from intermediate cells, MCAs, which in turn are derived from induced pluripotent stem cells or iPSCs. The iPSCs used in the Cymerus™ process were derived from blood donated by a fully-consented healthy adult donor, and were reprogrammed using a transgene-free, viral-free and feeder-free technique.
The PI or authorised designee will ensure that the study treatment at site is safely handled and administered in compliance with requirements. The infusion of the treatment itself will last no longer than 40 minutes, at a rate of 1mL/min, administered via ICU staff.
Intervention code [1] 317601 0
Treatment: Other
Comparator / control treatment
The control group receives standard care in adult ICU. This is defined as all interventions received as part of routine clinical practice for the management of COVID-19 or related illnesses in ICU that does not include the study intervention of CYP-001.
Control group
Active

Outcomes
Primary outcome [1] 323814 0
To evaluate the early efficacy of CYP-001 in adults with respiratory failure being treated in intensive care units (ICU), based on improvements in P/F ratio compared to controls. This outcome is defined as a trend in trajectory of P/F ratio between groups by day 7. P/F ratio is collected from ventilatory support data combined with arterial blood gas measures
Updated from
To evaluate the early efficacy of CYP-001 in adults with COVID-19 being treated in intensive care units (ICU), based on improvements in P/F ratio compared to controls. This outcome is defined as a trend in trajectory of P/F ratio between groups by day 7. P/F ratio is collected from ventilatory support data combined with arterial blood gas measures  
Reason: Protocol Amendment amde after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM
Updated from
To evaluate the early efficacy of CYP-001 in adults with COVID-19 being treated in intensive care units (ICU), based on improvements in P/F ratio compared to controls. This outcome is defined as a proportion of participants showing a 50% improvement in P/F ratio by day 7. P/F ratio is collected from ventilatory support data combined with arterial blood gas measures
  
Reason: Since submission of the original procedures, NSW Health hospitals have analysed COVID-19 patient outcome data and the outcomes of this study now reflect meaningful and realistic changes. Updates to this outcome were implemented prior to any patient enrolments.
Updated on 17/12/2020 10:56:15 AM
Timepoint [1] 323814 0
By day 7 in the study (within days 1-7). P/F ratio will be collected as per routine standard collection of data to inform respiratory function (at least 4 hourly when relevant) plus every 15 minutes during cell adminstration and 1, 2, 3, 4 and 5 hours after
Updated from
By day 7 after enrolment in the study (within days 1-7). P/F ratio will be collected as per routine standard collection of data to inform respiratory function (at least 4 hourly when relevant) plus every 15 minutes during cell adminstration and 1, 2, 3, 4 and 5 hours after  
Reason: Language has been clarified.
Updated on 17/12/2020 10:56:15 AM
Primary outcome [2] 323815 0
To assess the safety and tolerability of CYP-001 in adults with respiratory failure being treated in ICU measured by the incidence and severity of treatment-emergent adverse events (including events related with reactions to cryoprotectant; fever read from digital thermometer, allergy, olfactory/taste disturbances), safety laboratory evaluations (immunology screen with full blood examination) and vital signs (including significant fluctuations from clinically acceptable BP, and HR and SaO2 levels measured via pulse oximetry)
Updated from
To assess the safety and tolerability of CYP-001 in adults with COVID-19 being treated in ICU measured by the incidence and severity of treatment-emergent adverse events (including events related with reactions to cryoprotectant; fever read from digital thermometer, allergy, olfactory/taste disturbances), safety laboratory evaluations (immunology screen with full blood examination) and vital signs (including significant fluctuations from clinically acceptable BP, and HR and SaO2 levels measured via pulse oximetry)  
Reason: Protocol Amendment made after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM
Timepoint [2] 323815 0
Up to day 28 in the study. On days 0-7 this will be collected routinely in standard care (at least 4-hourly) plus every 15 minutes during cell administration and 1, 2, 3, 4 and 5 hours after, then daily after day 8
Updated from
Up to day 28 after enrolment in the study. On days 0-7 this will be collected routinely in standard care (at least 4-hourly) plus every 15 minutes during cell administration and 1, 2, 3, 4 and 5 hours after, then daily after day 8  
Reason: Language has been clarified
Updated on 17/12/2020 10:56:15 AM
Secondary outcome [1] 382972 0
To evaluate the early efficacy of CYP-001 in adults with respiratory failure being treated in ICU, measured by changes in blood inflammatory marker, C-reactive protein
Updated from
To evaluate the early efficacy of CYP-001 in adults with COVID-19 being treated in ICU, measured by changes in blood inflammatory marker, C-reactive protein  
Reason: Protocol Amendment made after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM
Timepoint [1] 382972 0
Up to day 7 after patient enrolment in study, collected as part of standard care pathology analysis occurring daily
Updated from
Up to day 7 after enrolment, collected as part of standard care pathology analysis occurring daily  
Reason: Language has been clarified.
Updated on 17/12/2020 10:56:15 AM
Secondary outcome [2] 382974 0
To evaluate the early efficacy of CYP-001 in adults with respiratory failure being treated in ICU, based on changes in physiological indices of respiratory dysfunction (including exploratory measures of P/F ratio, respiratory rate, oxygenation index (OI), respiratory compliance, positive end-expiratory pressure (PEEP), fever monitoring, ICU length of stay, ventilator free days (VFDs)) from data collected routinely in standard care (i.e. records of extubation, reintubation) up to day 28.
Updated from
To evaluate the early efficacy of CYP-001 in adults with COVID-19 being treated in ICU, based on changes in physiological indices of respiratory dysfunction (including exploratory measures of P/F ratio, respiratory rate, oxygenation index (OI), respiratory compliance, positive end-expiratory pressure (PEEP), fever monitoring, ICU length of stay, ventilator free days (VFDs)) from data collected routinely in standard care (i.e. records of extubation, reintubation) up to day 28.  
Reason: Protocol Amendment made after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM
Updated from
To evaluate the early efficacy of CYP-001 in adults with COVID-19 being treated in ICU, based on changes in physiological indices of respiratory dysfunction (including exploratory measures of respiratory rate, oxygenation index (OI), respiratory compliance, positive end-expiratory pressure (PEEP), ventilator free days (VFDs)) from data collected routinely in standard care  
Reason: Updated missing evaluations. Changes to this outcome were implemented prior to any patient enrolments.
Updated on 17/12/2020 10:56:15 AM
Timepoint [2] 382974 0
Up to day 28 after patient enrolment in study, collected as per routine standard collection of data to inform respiratory function (at least 4 hourly when relevant) and at the same intervals as P/F ratio
Updated from
Up to day 28 after enrolment, collected as per routine standard collection of data to inform respiratory function (at least 4 hourly when relevant) and at the same intervals as P/F ratio  
Reason: Language has been clarified.
Updated on 17/12/2020 10:56:15 AM
Secondary outcome [3] 383086 0
To evaluate the early efficacy of CYP-001 in adults with respiratory failure being treated in ICU, based on proportional differences between groups on the Clinical Improvement Scale
Updated from
To evaluate the early efficacy of CYP-001 in adults with COVID-19 being treated in ICU, based on proportional differences between groups on the Clinical Improvement Scale  
Reason: Protocol Amendment made after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM
Timepoint [3] 383086 0
Assessed on day 28 after patient enrolment in study, based on health and hospitalisation status
Updated from
Assessed on day 28 after enrolment based on health and hospitalisation status  
Reason: Language has been clarified.
Updated on 17/12/2020 10:56:15 AM
Secondary outcome [4] 383087 0
To evaluate the early efficacy of CYP-001 in adults with respiratory failure being treated in ICU, based on proportional differences between groups in Quality of Life and Disability assessments measured by the 36-Item Short Form Survey (SF-36)
Updated from
To evaluate the early efficacy of CYP-001 in adults with COVID-19 being treated in ICU, based on proportional differences between groups in Quality of Life and Disability assessments measured by the 36-Item Short Form Survey (SF-36)  
Reason: Protocol Amendment made after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM
Timepoint [4] 383087 0
Assessed on day 28 after patient enrolment in study
Updated from
Assessed on day 28 after enrolment  
Reason: Language has been clarified.
Updated on 17/12/2020 10:56:15 AM
Secondary outcome [5] 383221 0
To evaluate the early efficacy of CYP-001 in adults with respiratory failure being treated in ICU, based on proportional differences between groups in Quality of Life and Disability assessments measured by the Standardised Mini-Mental State Examination (SMMSE)
Updated from
To evaluate the early efficacy of CYP-001 in adults with COVID-19 being treated in ICU, based on proportional differences between groups in Quality of Life and Disability assessments measured by the Standardised Mini-Mental State Examination (SMMSE)  
Reason: Protocol Amendment made after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM
Timepoint [5] 383221 0
Assessed on day 28 after patient enrolment in study
Updated from
Assessed on day 28 after enrolment  
Reason: Language has been clarified.
Updated on 17/12/2020 10:56:15 AM

Eligibility
Key inclusion criteria
1. Male or female, 18 years of age or older
2. Respiratory failure with the following signs and symptoms:
P/F ratio <300 mmHg
Onset within one week of insult or new or worsening respiratory symptoms.
Chest imaging shows bilateral opacities, which are not fully explained by effusions,
lobar/lung collapse, or nodules.
3. Respiratory failure which is not fully explained by cardiac failure or fluid overload.
4. Onset of respiratory failure (as defined in inclusion criterion 2) within the past 48 hours.
Updated from
1. Male or female, 18 years of age or older<br />2. ICU admission due to strongly suspected or proven COVID-19<br />3. P/F ratio <300 mmHG within the past 24 hours, but not sustained for more than 24 hours at the time of enrolment  
Reason: Protocol Amendment made after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM
Updated from
1. Male or female, 18 years of age or older<br />2. ICU admission due to strongly suspected or proven COVID-19<br />3. P/F ratio <300 mmHG for less than 24 hours  
Reason: Language updated for clarification
Updated on 17/12/2020 10:56:15 AM
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. <18 years of age
2. Patient is known to be pregnant
3. Known active malignancy that required treatment in the last year
4. WHO (2019) Class III, IV or V pulmonary hypertension
5. Venous thromboembolism currently receiving anti-coagulation or within the past 3 months
6. Currently receiving extracorporeal life support
7. Severe chronic liver disease (Child-Pugh score >12)
8. “Do Not Attempt Resuscitation” order in place
9. Treatment withdrawal imminent within 24 hours
10. BMI > 45 kg/m2.
11. Received any investigational research agent within 60 days or within five half-lives of the last treatment (if the half-life of the investigational agent is known to be longer than 12 days) prior to the planned administration of study treatment.
12. Known positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus, Hepatitis C virus or any other infection which the opinion of the Investigator is likely to impact on the ability of the patient to participate in the study.
13. Known sensitivity to DMSO or any other component of the study treatments.
Updated from
1. <18 years of age<br />2. Patient is known to be pregnant<br />3. Known active malignancy that required treatment in the last year<br />4. WHO Class III or IV pulmonary hypertension<br />5. Venous thromboembolism currently receiving anti-coagulation or within the past 3 months<br />6. Currently receiving extracorporeal life support<br />7. Severe chronic liver disease (Child-Pugh score >12)<br />8. “Do Not Attempt Resuscitation” order in place<br />9. Treatment withdrawal imminent within 24 hours<br />10. BMI > 45 kg/m2.<br />11. Received any investigational research agent within 60 days or within five half-lives of the last treatment (if the half-life of the investigational agent is known to be longer than 12 days) prior to the planned administration of study treatment.<br />12. Known positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus, Hepatitis C virus or any other infection which the opinion of the Investigator is likely to impact on the ability of the patient to participate in the study.<br />13. Known sensitivity to DMSO or any other component of the study treatments.  
Reason: Protocol Amendment made after enrolment of 5 participants
Updated on 5/05/2022 10:10:15 AM

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Updated from
Recruiting  
Reason: update
Updated on 12/04/2023 2:03:51 PM
Updated from
Not yet recruiting  
Reason: This trial is now open for recruitment
Updated on 10/09/2020 12:07:33 PM
Date of first participant enrolment
Anticipated
30/06/2023
Actual
22/05/2021
Updated from
1/06/2020 
Reason: Protocol Amendment
Updated on 5/05/2022 10:10:15 AM
Updated from
 
Reason: update
Updated on 12/04/2023 2:03:51 PM
Date of last participant enrolment
Anticipated
Actual
14/04/2022
Updated from
 
Reason: update
Updated on 12/04/2023 2:03:51 PM
Date of last data collection
Anticipated
Actual
14/05/2022
Updated from
 
Reason: update
Updated on 12/04/2023 2:03:51 PM
Sample size
Target
24
Accrual to date
Final
14
Updated from
0 
Reason: Recruitment complete
Updated on 12/04/2023 2:03:51 PM
Updated from
 
Reason: Field is updated as study is now open for recruitment
Updated on 10/09/2020 12:07:33 PM
Updated from
 
Reason: update
Updated on 12/04/2023 2:03:51 PM
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Updated from
NSW  
Reason: Victorian sites added
Updated on 22/03/2021 9:43:11 AM
Recruitment hospital [1] 16683 0
Westmead Hospital - Westmead
Recruitment hospital [2] 16684 0
Nepean Hospital - Kingswood
Recruitment hospital [3] 18977 0
Footscray Hospital - Footscray
Inserted
 
Reason: New site, Victoria
Updated on 22/03/2021 9:43:11 AM
Recruitment hospital [4] 18978 0
Sunshine Hospital - St Albans
Inserted
 
Reason: New site, Victoria
Updated on 22/03/2021 9:43:11 AM
Recruitment hospital [5] 22329 0
St George Hospital - Kogarah
Inserted
 
Reason: New site
Updated on 9/05/2022 9:52:30 AM
Recruitment postcode(s) [1] 30278 0
2145 - Westmead
Recruitment postcode(s) [2] 37490 0
2217 - Kogarah
Inserted
 
Reason: New site
Updated on 9/05/2022 9:52:30 AM
Recruitment postcode(s) [3] 30279 0
2747 - Kingswood
Recruitment postcode(s) [4] 33484 0
3011 - Footscray
Inserted
 
Reason: New site, Victoria
Updated on 22/03/2021 9:43:11 AM
Recruitment postcode(s) [5] 33485 0
3021 - St Albans
Inserted
 
Reason: New site, Victoria
Updated on 22/03/2021 9:43:11 AM

Funding & Sponsors
Funding source category [1] 305737 0
Commercial sector/Industry
Name [1] 305737 0
Cynata Therapeutics Limited
Country [1] 305737 0
Australia
Funding source category [2] 305768 0
Charities/Societies/Foundations
Name [2] 305768 0
Cerebral Palsy Alliance Research Institute
Country [2] 305768 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Cynata Therapeutics Limited
Address
Level 3, 100 Cubitt Street Cremorne Victoria 3121 Australia
Updated from
Level 3, 62 Lygon Street,<br />Carlton<br />VIC 3053<br />Australia  
Reason: New address
Updated on 5/05/2022 10:10:15 AM
Country
Australia
Secondary sponsor category [1] 306161 0
None
Name [1] 306161 0
Address [1] 306161 0
Country [1] 306161 0
Other collaborator category [1] 281313 0
Charities/Societies/Foundations
Name [1] 281313 0
Cerebral Palsy Alliance Research Institute
Address [1] 281313 0
187 Allambie Road
Allambie Heights
NSW 2086
Australia
Country [1] 281313 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306010 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 306010 0
123 Glen Osmond Road
Eastwood, South Australia
5063
Ethics committee country [1] 306010 0
Australia
Date submitted for ethics approval [1] 306010 0
Approval date [1] 306010 0
07/05/2020
Ethics approval number [1] 306010 0

Summary
Brief summary
The purpose of this study is to assess the early efficacy of mesenchymal stem cells (Cynata Therapeutics Limited, CYP-001) in adults admitted to intensive care with Respiratory Distress due to COVID-19 or another underlying condition.
Updated from
The purpose of this study is to assess the early efficacy of mesenchymal stem cells (Cynata Therapeutics Limited, CYP-001) in adults admitted to intensive care with COVID-19.  
Reason: Protocol amendment made after enrolment of 5 participants.
Updated on 5/05/2022 10:10:15 AM
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102410 0
A/Prof Vineet Nayyar
Address 102410 0
Westmead Hospital
Cnr Hawkesbury Road and, Darcy Rd,
Westmead NSW 2145
Country 102410 0
Australia
Phone 102410 0
+61 2 8890 9363
Fax 102410 0
Email 102410 0
Vineet.Nayyar@health.nsw.gov.au
Contact person for public queries
Name 102411 0
Dr Kilian Kelly
Updated from
Madison Paton  

Updated on 5/05/2022 10:10:15 AM
Address 102411 0
Cynata Therapeutics Limited, Level 3, 100 Cubitt Street Cremorne Victoria 3121 Australia
Updated from
Cerebral Palsy Alliance Research Institute
Site address: Brain and Mind Centre,
Level 4 Building M02C
88 Mallett Street, Camperdown, NSW 2050
Postal address: PO Box 6427, Frenchs Forest, NSW 2086  

Updated on 5/05/2022 10:10:15 AM
Country 102411 0
Australia
Phone 102411 0
+61 3 982 45254
Updated from
+61 2 8052 2059  

Updated on 5/05/2022 10:10:15 AM
Fax 102411 0
Email 102411 0
kilian.kelly@cynata.com
Updated from
madison.paton@cerebralpalsy.org.au  

Updated on 5/05/2022 10:10:15 AM
Contact person for scientific queries
Name 102412 0
Dr Kilian Kelly
Address 102412 0
Cynata Therapeutics Limited, Level 3, 100 Cubitt Street Cremorne Victoria 3121 Australia
Updated from
Cynata Therapeutics Limited
Level 3, 62 Lygon Street,
Carlton
VIC 3053
Australia  

Updated on 5/05/2022 10:10:15 AM
Country 102412 0
Australia
Phone 102412 0
+61 3 982 45254
Fax 102412 0
Email 102412 0
kilian.kelly@cynata.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD relating to efficacy of MSCs in respiratory failure (including COVID-19) may be shared, subject to permission from Sponsor and ethics approval if required. All de-identified data collected during this study may be shared confidentially to contribute to meta-analysis of mesenchymal stem cell treatments for respiratory failure. Request for IPD from this trial for other purposes will be considered by the Sponsor
Updated from
IPD relating to efficacy of MSCs in COVID-19 may be shared, subject to permission from Sponsor and ethics approval if required. All de-identified data collected during this study may be shared confidentially to contribute to meta-analysis of mesenchymal stem cell treatments for COVID-19. Request for IPD from this trial for other purposes will be considered by the Sponsor  

Updated on 5/05/2022 10:10:15 AM
When will data be available (start and end dates)?
All reasonable requests for raw and analysed data that are not included in primary publications from this study may be available upon request and discretion from the Sponsor from the beginning to the trial. There is no specified end date
Available to whom?
Data may be made available to active collaborators in the COVID-19 Stem Cell Treatment (CSCT) Group, subject to permission from the Sponsor and ethics approval if required. All other reasonable requests for raw and analysed data will be considered by the Sponsor
Available for what types of analyses?
IPD data analysis for efficacy, determination of responders and non-responders, and harmonisation of efficacy endpoints across MSC clinical trials
How or where can data be obtained?
Data may be obtained upon permission from the Sponsor. The Sponsor can be contacted by emailing: clinical@cynata.com


What supporting documents are/will be available?

No Supporting Documents Provided
Results publications and other study-related documents

No Study Results Provided