MRG-001 as an Immunoregulatory and Regenerative Therapy for COVID-19 Patients
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MRG-001 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
Subjects will receive subcutaneous MRG-001 injections.
|
| Placebo Comparator: Placebo 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
Subjects will receive subcutaneous placebo injections.
|
Outcome Measures
Primary Outcome Measures
- Safety and Tolerability [60 days]
To evaluate the safety (SAE's) of MRG-001 in Severe and Critical SARS-CoV-2 patients.
Secondary Outcome Measures
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria
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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.
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Males and females over 18 years of age, inclusive, at the time of signing the ICF.
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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.
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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.
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Radiologic findings compatible with diagnosis of SARS-CoV-2 pulmonary infection.
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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.
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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
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Participation in any other clinical trial of an experimental treatment for COVID-19 (remdesivir use is permitted).
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Significant pre-existing organ dysfunction prior to randomization
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Lung: Receiving supplemental home oxygen therapy at baseline for pre-existing medical condition (other than COVID-19), as documented in medical record
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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.
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Renal: End-stage renal disease requiring renal replacement therapy or eGFR <30 mL/min
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Liver: Severe chronic liver disease defined as Child-Pugh Class C
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Hematologic: Baseline platelet count <50,000/mm3
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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.
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History of splenectomy or splenomegaly (spleen weighing >750 g).
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Body mass index of >45 kg/m2 at screening
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Underlying malignancy, or other condition, with estimated life expectancy of less than two months
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Known family history of long QT syndrome (Torsades de Pointes) or currently taking medication that prolongs QT interval.
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Currently taking immunomodulating biologics (e.g., interferons, interleukin).
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Extracorporeal membrane oxygenation (ECMO).
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Use of two or more vasopressors.
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Female subjects who are pregnant or breastfeeding or planning to breastfeed at any time through 90 days after last dose of IP.
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Received a live-attenuated vaccine within 30 days prior to enrollment.
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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.
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Ongoing immunosuppression: solid organ transplant recipients.
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Has used an investigational drug within 30 days prior to Screening.
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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.
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Current treatment with an anti-viral medication for COVID-19 (e.g. hydroxychloroquine, lopinavir/ritonavir), other than remdesivir.
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Unable to understand the protocol requirements, instructions and study related restrictions, the nature, scope and possible consequences of the clinical study.
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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.
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Previously been enrolled in this clinical study.
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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).
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Any condition that in the opinion of the treating physician will increase the risk for the participant.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Johns Hopkins Medicine | Baltimore | Maryland | United States | 21205 |
Sponsors and Collaborators
- MedRegen LLC
- ICON plc
- Johns Hopkins University
Investigators
- Principal Investigator: Russell N Wesson, M.B.Ch.B, Johns Hopkins University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MRG2020