A Study to Collect Bone Marrow for Process Development and Production of BM-MSC to Treat Severe COVID19 Pneumonitis

Study Overview
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Brief Summary
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The COVID-19 pandemic, commonly referred to as coronavirus, first began in the city of Wuhan, China in December 2019. This virus has since spread globally, with infections reported in nearly every country. COVID-19 targets the body's respiratory system, where infections can be found in the nose, throat and lungs. The effect of COVID-19 infection is very variable, where many people might not know that they have been infected and have recovered from COVID-19. However, COVID-19 infection can cause people to have difficulty breathing. This can be severe enough to require hospitalisation and potentially intensive care treatment. While they are being treated in hospital, COVID-19 infected patients can be found to have inflamed tissue in their lungs (referred to medically as pneumonitis). This inflammation is thought to be caused by their body's immune systems overacting to the infection rather than the COVID-19 virus itself. By potentially dampening down this overreaction of their immune system, it is hoped that COVID-19 patients with inflamed lungs have better and quicker chance to survive. Mesenchymal stromal cells (MSCs) have been shown to have anti-inflammatory and healing properties on injured tissue. MSCs have been trialled in various diseases but have not yet been tested on patients with COVID-19. In this study, the investigators will obtain bone marrow from healthy volunteers to develop a cell-based treatment for COVID-19-related pneumonitis. The investigators will also determine whether it is feasible to recruit bone marrow donors in a clinically useful timeframe to treat COVID-19 patients. A future trial, COMET20, will use the bone marrow-derived MSCs (BM-MSCs) manufactured in COMET20d to treat COVID-19 patients suffering with pneumonitis, to determine whether the BMMSCs can reduce the likelihood for mechanical ventilation and reduce hospitalisation.

Official Title
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A Study to Collect Bone Marrow for Process Development and Production of Bone Marrow Mesenchymal Stromal Cells to Treat Severe COVID19 Pneumonitis

Conditions
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Healthy Volunteers for Bone Marrow Donation

Intervention / Treatment
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* Procedure: Bone Marrow Harvest


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have given written informed consent to participate Be aged between 18 and 40 years old Have Eastern Cooperative Oncology Group (ECOG) performance status 0 Be negative for mandatory infectious disease markers (IDM) as per World Marrow Donor Association (WMDA) guidelines Present a negative SARS-CoV2 screen Show absence of clinical symptoms of COVID-19 (Not have been in known COVID-19 contact within the previous 14 days, Adherence to national social distancing guidelines for 14 days) Have a BMI <35kg/m^2 Women of childbearing potential need a negative pregnancy test (urine or blood) within 7 days prior to the marrow collection Exclusion Criteria: Any major disease which would represent a contraindication to bone marrow donation based on WMDA guidelines Presence of any previous or active malignancy (other than non-melanoma skin cancer) Any other concurrent severe and/or uncontrolled medical condition Women who are pregnant or breast-feeding Any acute or chronic back complaint Presence of anaesthetic risk factors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Volunteer<br>A one time only 30-80 mL sample of bone marrow will be collected from both posterior superior iliac crests. | Procedure: Bone Marrow Harvest<br>* Healthy volunteer bone marrow harvest<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine feasibility of recruiting healthy volunteers in a clinically useful timeframe. | Successful identification of healthy volunteers in acceptable timeframe (i.e. within days) to donate bone marrow. | 3 or more participants recruited in 1 month | 
| Manufacture a cell-based product suitable for clinical use | Successful manufacture of bone marrow-mesenchymal stromal cells suitable for clinical use | Successfully opening the next phase of the trial in approx. 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establishment of a robust process of production | Ability to prepare a dossier acceptable to the MHRA. Success will achieved if the dossier is deemed acceptable. | Successfully opening the next phase of the trial in approx. 2 months | 
| Production of stability data to be used in the MHRA dossier for the COMET clinical trial. | Successful manufacturing of products will be defined initially as the award of a Manufacturers Specials Licence to the CCTL to allow the manufacture of Bone Marrow-Mesenchymal Stromal Cells for compassionate use. | Successfully opening the next phase of the trial in approx. 2 months | 
| Production of cell-based products to be administered to COVID-19 patients with severe pneumonitis. | Successful manufacturing of products will be subsequently defined by production under MA(IMP) licence, allowing for future production under CTIMP and CTA. | Successfully opening the next phase of the trial in approx. 2 months | 
| Analysis of cells for understanding production, manufacture and related research. | Successful manufacturing of products, under MA(IMP) licence will be defined as the availability of Bone Marrow-Mesenchymal Stromal Cells to be used in the context of the COMET20 clinical trial. | Successfully opening the next phase of the trial in approx. 2 months |