Overview
MRG-001 as an Immunoregulatory and Regenerative Therapy for COVID-19 Patients
Status:
Active, not recruiting
Active, not recruiting
Trial end date:
2022-03-01
2022-03-01
Target enrollment:
0
0
Participant gender:
All
All
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).Phase:
Phase 1/Phase 2Accepts Healthy Volunteers?
Accepts Healthy VolunteersDetails
Lead Sponsor:
MedRegen LLCCollaborators:
ICON plc
Kendall Healthcare Group, Ltd.
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) 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.