MRG-001 as an Immunoregulatory and Regenerative Therapy for COVID-19 Patients

Study Overview
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Brief Summary
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This study consists of two parts. Part A (Phase I): A Phase I Double-blind Randomized Placebo-controlled Study in Healthy Subjects to Assess the Safety, Pharmacokinetics, Pharmacodynamics of MRG-001 Part B (Phase 2): A Phase IIa, Adaptive, Double-Blind, Randomized, Placebo-controlled, Multi-center Study in Hospitalized Patients Infected with Severe and Critical SARS-CoV-2 to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of MRG-001

Detailed Description
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MRG-001 is a fixed-dose combination (FDC) drug, administered as a single subcutaneous (SC) injection. Preclinical studies have demonstrated a synergistic effect of these 2 APIs in mobilizing and recruiting stem cells/immunoregulatory cells and promoting tissue regeneration in a wide variety of studies. MRG-001 is likely to target multiple aspects of the COVID-19. MRG-001 exhibits immunoregulatory and regenerative properties in preclinical studies with a wide variety of diseases. Repairing damaged tissues in the lung and other organs, restoring the anti-virus immune system and modulating the inflammation are obvious therapeutic targets for COVID-19. Part A has been completed in May 01, 2021. Part B has been initiated in January 2022.

Official Title
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A Phase IIa, Adaptive, Double-Blind, Randomized, Placebo-Controlled, Multi-Center Study in Hospitalized Patients Infected With Severe and Critical SARS-CoV-2 to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of MRG-001

Conditions
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COVID-19, ARDS, Human, Stem Cells, Regeneration

Intervention / Treatment
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* Drug: MRG-001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subject voluntarily agrees to participate in this study and is able to provide written informed consent or has a legal representative who can provide informed consent. Males and females over 18 years of age, inclusive, at the time of signing the ICF. Hospitalized, with COVID-19 symptoms of respiratory illness caused by SARS-CoV-2 infection (defined as Scale 5 - 7 on the WHO 8-point ordinal scale for clinical improvement. Laboratory-confirmation SARS-CoV-2 by real time polymerase chain reaction in the respiratory tract (NP swab, oropharyngeal swab, tracheal aspirate, BAL) </=14 days prior to randomization. Radiologic findings compatible with diagnosis of SARS-CoV-2 pulmonary infection. Women of childbearing potential must be willing and able to use at least one highly effective contraceptive method for a period from the screening visit until the end of study visit. Men must be willing to use a double-barrier contraception from enrollment until at 5 months after the last dose of study drug, if not abstinent. Exclusion Criteria 1. Participation in any other clinical trial of an experimental treatment for COVID-19 (remdesivir use is permitted). 2. Significant pre-existing organ dysfunction prior to randomization Lung: Receiving supplemental home oxygen therapy at baseline for pre-existing medical condition (other than COVID-19), as documented in medical record Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% as documented in the medical record. clinically significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), unstable angina, myocardial infarction (past 3 months), heart and coronary vessel surgery (past 3 months), significant valvular heart disease, uncontrolled arterial hypertension with systolic blood pressure >180 mm Hg and diastolic blood pressure >110 mm Hg. Renal: End-stage renal disease requiring renal replacement therapy or eGFR <30 mL/min Liver: Severe chronic liver disease defined as Child-Pugh Class C Hematologic: Baseline platelet count <50,000/mm3 2. Concurrent treatment or prior use of drugs with actual or possible direct acting immunomodulatory activity against ARDS in COVID-19 is prohibited including JAK1/JAK2 inhibitor ruxolitinib, baricitinib and tofacitinib. However, IL-6 inhibitors such as tocilizumab, sarilumab are allowed if given >72 hours prior to first study dose. Corticosteroids are permitted throughout the study. 3. History of splenectomy or splenomegaly (spleen weighing >750 g). 4. Body mass index of >45 kg/m2 at screening 5. Underlying malignancy, or other condition, with estimated life expectancy of less than two months 6. Known family history of long QT syndrome (Torsades de Pointes) or currently taking medication that prolongs QT interval. 7. Currently taking immunomodulating biologics (e.g., interferons, interleukin). 8. Extracorporeal membrane oxygenation (ECMO). 9. Use of two or more vasopressors. 10. Female subjects who are pregnant or breastfeeding or planning to breastfeed at any time through 90 days after last dose of IP. 11. Received a live-attenuated vaccine within 30 days prior to enrollment. 12. Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, human immunodeficiency virus (HIV) antibody or Active tuberculosis or a history of inadequately treated tuberculosis. 13. Ongoing immunosuppression: solid organ transplant recipients. 14. Has used an investigational drug within 30 days prior to Screening. 15. History of hypersensitivity to MRG-001 (plerixafor [AMD3100, 24 mg/mL]) and tacrolimus [FK506, 0.5 mg/mL]) or any of the excipients or to medicinal products with similar chemical structures. 16. Current treatment with an anti-viral medication for COVID-19 (e.g. hydroxychloroquine, lopinavir/ritonavir), other than remdesivir. 17. Unable to understand the protocol requirements, instructions and study related restrictions, the nature, scope and possible consequences of the clinical study. 18. Unlikely to comply with the protocol requirements, instructions and study related restrictions, e.g., uncooperative attitude, inability to return for follow-up visits and improbability of completing the clinical study. 19. Previously been enrolled in this clinical study. 20. Vulnerable subjects defined as individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate (e.g., persons in detention, minors and those incapable of giving consent). 21. Any condition that in the opinion of the treating physician will increase the risk for the participant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-Blind Randomized Placebo-Controlled Trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRG-001<br>Multiple SC dose of 0.0066 mL/kg MRG-001 (n=20) will be administered every other day for the duration of 13 days totaling 7 injections. | Drug: MRG-001<br>* Subjects will receive subcutaneous MRG-001 injections.<br>|
| Placebo Comparator: Placebo<br>Single SC dose of 0.0066 mL/kg Sterile Injectable Saline (n=20) will be administered every other day for the duration of 13 days totaling 7 injections. | Drug: Placebo<br>* Subjects will receive subcutaneous placebo injections.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | To evaluate the safety (SAE's) of MRG-001 in Severe and Critical SARS-CoV-2 patients. | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percentages from baseline in circulating white blood cell subpopulations |  | 15 days | 
| Change in Plerixafor concentration (ng/ml) from baseline in blood |  | 15 days | 
| Change in Tacrolimus concentration (ng/ml) from baseline in blood |  | 15 days | 
| Change from baseline in ALT, AST, INR, Albumin, Bilirubin, LDH, BUN, eGFR |  | 15 days | 
| Change in percentages from baseline in circulating stem cells and immune cells |  | 15 days | 
| All-cause mortality assessed at 14, 28 and 60 days following randomization. |  | 60 days | 
| Time to clinical improvement from randomization by at least 2 points on the 8-point ordinal scale of WHO clinical improvement scale assessed up to 14 and 60 days (1=Asymptomatic, no limitations of activities; 8=death). |  | 60 days |