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

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ClinicalTrials.gov Identifier: NCT04646603
Recruitment Status : Active, not recruiting
First Posted : November 30, 2020
Last Update Posted : August 19, 2021
Sponsor:
Collaborator:
ICON plc
Information provided by (Responsible Party):
MedRegen LLC

Brief Summary:

A Combined Phase I Double-blind Randomized Placebo-controlled Study in Healthy Subjects/Phase II, Randomized, Double-blind, 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 (Plerixafor Plus Low-dose Tacrolimus)

Part A: To determine the safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) profiles of MRG-001 in healthy subjects.

Part B: Time to clinical improvement from randomization by at least 2 points on the 8-point ordinal scale of WHO clinical improvement scale assessed at 14, 28 and 60 days (1=Asymptomatic, no limitations of activities; 8=death).


Condition or disease Intervention/treatment Phase
COVID-19 Drug: MRG-001 Drug: Placebo Phase 1 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. The combined phase I/IIa trial will involve 98 subjects (18 healthy volunteers and 80 COVID-19 patients) randomized into blinded placebo and MRG-001 arms, to determine the safety and efficacy profile of MRG-001 as the primary endpoint.

Part A: The study has been completed on 05/07/2021. Data analysis will be initiated upon database lock.

Part B: The study is expected to start recruitment on 06/15/2021.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-Blind Randomized Placebo-Controlled Trial
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Combined Phase I Double-blind Randomized Placebo-controlled Study in Healthy Subjects/Phase II, Randomized, Double-blind, 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 (Plerixafor Plus Low-dose Tacrolimus)
Actual Study Start Date : January 28, 2021
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : March 1, 2022

Arm Intervention/treatment
Experimental: MRG-001

Single SC dose of 0.005 mL/kg MRG-001 (n=4) will be administered every other day for the duration of 5 days totaling 3 injections.

Single SC dose of 0.01 mL/kg MRG-001 (n=4) will be administered every other day for the duration of 5 days totaling 3 injections.

Single SC dose of 0.02 mL/kg MRG-001 (n=4) will be administered every other day for the duration of 5 days totaling 3 injections.

Drug: MRG-001
Subjects will receive subcutaneous MRG-001 injections.

Placebo Comparator: Placebo

Single SC dose of 0.005 mL/kg Sterile Injectable Saline (n=2) will be administered every other day for the duration of 5 days totaling 3 injections.

Single SC dose of 0.01 mL/kg Sterile Injectable Saline (n=2) will be administered every other day for the duration of 5 days totaling 3 injections.

Single SC dose of 0.02 mL/kg Sterile Injectable Saline (n=2) will be administered every other day for the duration of 5 days totaling 3 injections.

Drug: Placebo
Subjects will receive subcutaneous placebo injections.




Primary Outcome Measures :
  1. Phase I [ Time Frame: 12 days ]
    Change from baseline in the proportion of subjects experiencing any treatment emergent adverse event (TEAE) associated with MRG-001 to Day 12.

  2. Phase IIa [ Time Frame: 28 days ]
    Time to clinical improvement from randomization to Day 28 by at least 2 points on the 8-point ordinal scale of WHO clinical improvement scale (1 = discharged; 8 = death).


Secondary Outcome Measures :
  1. Change in percentages from baseline in circulating white blood cell subpopulations [ Time Frame: 12 days ]
  2. Change in Plerixafor concentration (ng/ml) from baseline in blood [ Time Frame: 12 days ]
  3. Change in Tacrolimus concentration (ng/ml) from baseline in blood [ Time Frame: 12 days ]
  4. Change from baseline in ALT, AST [ Time Frame: 12 days ]
  5. Change in percentages from baseline in circulating stem cells and immune cells [ Time Frame: 12 days ]
  6. Change from baseline in platelets [ Time Frame: 12 days ]
  7. Change from baseline in total Bilirubin [ Time Frame: 12 days ]
  8. Change from baseline in LDH [ Time Frame: 12 days ]
  9. Change from baseline in blood urea nitrogen (BUN) [ Time Frame: 12 days ]
  10. Change from baseline in glomerular filtration rate (GFR) [ Time Frame: 12 days ]
  11. Change from baseline in hemoglobin [ Time Frame: 12 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Subject voluntarily agrees to participate in this study and signs an Institutional Review Board (IRB)-approved informed consent prior to performing any of the Screening Visit procedures.
  2. Males and females between 18 to 45 years of age, inclusive, at the time of signing the ICF.
  3. Subjects who test negative for SARS-CoV-2 by real time transcription polymerase chain reaction in the respiratory tract (nasopharyngeal [NP] swab) within the previous 96 hours.
  4. Nonsmokers (or other nicotine use) as determined by history (no nicotine use over the past 6 months) and by urine cotinine concentration (< 500 ng/mL) at the Screening Visit and admission.
  5. Generally, in good health with no clinically significant abnormalities as determined by medical history, physical examination, 12-lead ECG and clinical laboratory tests.
  6. The following applies to female subjects:

    •Non-pregnant, non-lactating females of childbearing potential who agree to use medically acceptable forms of birth control (hormonal contraception, abstinence, diaphragm with spermicide, condom with spermicide or intrauterine device) from the Screening Visit until the End-of-study Visit.

  7. Body mass index (BMI) between 18.8 and 29.9 kg/m2, inclusive, at the Screening Visit.
  8. A fasting blood glucose level ≤125 mg/dL (6.9 mmol/L), at the Screening Visit.

Exclusion Criteria (Part A):

  1. Participation in any other clinical trial of an experimental treatment for COVID-19 (remdesivir and convalescent plasma use is permitted).
  2. Subject has clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological or psychiatric disorder(s) as determined by the PI or designee.
  3. Concurrent treatment with other agents with actual or possible direct acting immunomodulatory activity against ARDS in COVID-19 is prohibited <72 hours prior to study drug dosing [IL-6 inhibitors such as sarilumab and tocilizumab; IL-1β blocker; and the JAK1/JAK2 inhibitor ruxolitinib, barcitinib and tofacitinib; complement inhibitor ravulizumab-cwvz; Bruton's tyrosine kinase inhibitor acalabrutinib, and macrophage migration inhibitor ibudilast].
  4. History of splenomegaly (spleen weighing >750 g).
  5. History of cancer or thrombocytopenia (platelet count <100,000/µL) or thrombocythemia (platelet count >500,000/µL).
  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. Female subjects who are pregnant or breastfeeding or planning to breastfeed at any time through 90 days after last dose of study drug.
  9. Any disorder that would interfere with the absorption, distribution, metabolism or excretion of drugs.
  10. Received a vaccination (including influenza) administered 30 days or less prior to first treatment/randomization or has any planned vaccinations during the treatment period.
  11. Creatinine clearance <50 mL/min using the Cockcroft-Gault formula.
  12. Has the following liver function levels:

    Serum ALP or BIL >1.5 ULN or ALT or AST >ULN (Part A); Serum ALP or BIL >3.0 ULN or ALT or AST >5.0x ULN (Part B); at either screening or admission. Only 1 repeat assessment is allowed on each occasion.

  13. History of alcohol and/or illicit drug abuse within 2 years of entry.
  14. Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, or HIV antibody.
  15. Has a positive blood test for ethanol at the Screening Visit or admission.
  16. Has a positive urine drug test (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids) at the Screening Visit or admission.
  17. Has donated blood (>500 mL) or blood products within 2 months (56 days) prior to admission.
  18. Has used an investigational drug within 30 days prior to Screening.
  19. 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.
  20. Unable to understand the protocol requirements, instructions and study related restrictions, the nature, scope and possible consequences of the clinical study.
  21. 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.
  22. Previously been enrolled in this clinical study.
  23. 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).
  24. Laboratory-confirmation of SARS-CoV-2 by real time polymerase chain reaction in the respiratory tract (NP swab, tracheal aspirate, BAL) ≤96 hours prior to randomization.
  25. Is unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to screening until discharge from the clinical site.
  26. Is unable to abstain from smoking (or other nicotine use) from screening until discharge from the clinical site.
  27. Has any concurrent disease or condition that, in the opinion of the PI, would make the subject unsuitable for participation in the clinical study such as:

    1. Skin condition or disease (e.g., Stevens-Johnson syndrome).
    2. Hypertension defined as >140 mmHg systolic blood pressure and >95 mmHg diastolic blood pressure.
    3. High blood potassium (hyperkalemia) defined baseline serum potassium >5.0 to 5.5 mEq/L (milliequivalent).
    4. Torsades de Pointes or currently taking medication that prolongs QT interval.
    5. Hematologic disorder (e.g. anemia or leukemia).
    6. Type I or Type 2 diabetes mellitus defined as a fasting blood glucose level >126 mg/dL (7.0 mmol/L).

Inclusion Criteria (Part B)

  1. 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 or is enrolled under International Conference on Harmonization (ICH) E6 (R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (where permitted according to local law and approved nationally and by the relevant IRB) prior to performing any of the Screening Visit procedures.
  2. Males and females over 18 years of age, inclusive, at the time of signing the ICF.
  3. 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.
  4. Laboratory-confirmation SARS-CoV-2 by real time polymerase chain reaction in the respiratory tract (NP swab, tracheal aspirate, BAL) </= 14 days prior to randomization.
  5. Radiologic findings compatible with diagnosis of SARS-CoV-2 pulmonary infection
  6. 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. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as:

    1. combined (estrogen and progestogen containing) hormonal contraception combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal)
    2. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
    3. intrauterine device (IUD)
    4. intrauterine hormone-releasing system (IUS)
    5. vasectomized partner
    6. bilateral tubal occlusion
    7. true abstinence. when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence, such as calendar, ovulation, symptothermal, postovulation methods, and withdrawal are not acceptable methods of contraception.
  7. 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 (Part B)

  1. Participation in any other clinical trial of an experimental treatment for COVID-19 (remdesivir and convalescent plasma use is permitted).
  2. Significant pre-existing organ dysfunction prior to randomization Lung: Previously receiving home oxygen therapy at baseline, 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/mm^3

  3. Concurrent treatment with other agents with actual or possible direct acting immunomodulatory activity against ARDS in COVID-19 is prohibited <72 hours prior to study drug dosing [IL-6 inhibitors such as sarilumab and tocilizumab; IL-1β blocker; and the JAK1/JAK2 inhibitor ruxolitinib, barcitinib and tofacitinib; complement inhibitor ravulizumab-cwvz; Bruton's tyrosine kinase inhibitor acalabrutinib, and macrophage migration inhibitor ibudilast].
  4. History of splenomegaly (spleen weighing >750 g).
  5. Body mass index of >45 kg/m2 at screening
  6. Underlying malignancy, or other condition, with estimated life expectancy of less than two months
  7. Known family history of long QT syndrome (Torsades de Pointes) or currently taking medication that prolongs QT interval.
  8. Currently taking immunomodulating biologics (e.g, interferons, interleukin).
  9. Female subjects who are pregnant or breastfeeding or planning to breastfeed at any time through 90 days after last dose of IP.
  10. Received a live-attenuated vaccine within 30 days prior to enrollment
  11. Creatinine clearance less than 30 mL/min.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04646603


Locations
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United States, Texas
ICON Early Phase Services
San Antonio, Texas, United States, 78209
Sponsors and Collaborators
MedRegen LLC
ICON plc
Investigators
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Principal Investigator: George Atiee, MD ICON plc
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Responsible Party: MedRegen LLC
ClinicalTrials.gov Identifier: NCT04646603    
Other Study ID Numbers: MRG2020
First Posted: November 30, 2020    Key Record Dates
Last Update Posted: August 19, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Participants will be given a unique unidentifiable study ID number and all data will be recorded according to unidentifiable number to protect patients personal health information.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases