MRG-001 as an Immunoregulatory and Regenerative Therapy for ARDS Patients (SUMMIT)

A Phase IIa, Double-Blind, Randomized, Multi-Center Study Comparing MRG-001 to Placebo in Patients With Acute Respiratory Distress Syndrome

This is a phase IIa, dose-ranging, proof-of-concept study of MRG-001 in patients with ARDS.

The aim is to determine the safety and preliminary efficacy of MRG-001 across two dose ranges.

Study Overview

• Status: Not yet recruiting
• Conditions: Respiratory Tract Diseases; Respiratory Failure; Acute Respiratory Distress Syndrome; Respiratory Distress Syndrome; Cytokine Storm
• Intervention / Treatment: Drug: MRG-001 (Low-dose); Drug: MRG-001 (High-dose); Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: MedRegen LLC; Phone Number: 4437598563; Email: info@medregenco.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Acute Respiratory Distress Syndrome, manifested by the following and not explained by alternative diagnoses, for example but not limited to: Pulmonary Edema due to Congestive Heart Failure (CHF).

1. Chest x-ray (CXR)* revealing bilateral infiltrates involving a minimum of three quadrants on frontal chest radiograph, consistent with pulmonary edema or bilateral ground glass opacities not fully explained by effusions, lobar or lung collapse, nodules, atelectasis or other etiology of infiltrates not due to ARDS.
2. PaO2/FiO2 < 300.
3. Requiring respiratory support [defined as mechanical ventilation, non-invasive ventilation (NIV) or high flow nasal canula (HFNC)] If on ventilator, settings must include positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥5 cm H2O.

Exclusion Criteria:

1. Age less than 18 years.
2. Infiltrates with etiology suspected of mimicking ARDS, ie; Pulmonary Edema due to Congestive Heart Failure (CHF). (A Pulmonary Arterial Wedge Pressure (PAWP) of < 18 for >12 hours would rule out suspected CHF).
3. Pregnancy documented or suspected in women of child bearing potential, unless ruled out by a negative pregnancy test during screening or breast feeding.

4. Immunocompromised patients:

   4.1. Organ or bone marrow transplant recipients and/or recent (within 2 months) chronic use of immunosuppressive drugs (tacrolimus, mycofenolate mofetil, cyclosporine, rapamycine, hydrochloroquine, azathiopurine, methotrexate), e.g., biologicals, JAK1/2 inhibitors, interferons, interleukins, (prednisone or related corticosteroids are allowed).

   4.2. Patients with documented or suspected HIV/AIDS, hepatitis B/C or active lung disease with tuberculosis. 4.3. Patients with active cancer diagnosis or use of chemotherapy in the past 3 months.

5. Hypersensitivity to either of the components of MRG-001.
6. The patient is known or suspected to be brain dead or is moribund (not expected to live >48 hours) or is unlikely to survive long enough to receive 3 injections (4 days) in the opinion of the investigator.
7. The primary care physician is not committed to full support of the patient. (A DNR representing "no chest compression" only, would not necessarily be an exclusion. A DNR in which life support is withheld/withdrawn or is otherwise limited, would be an exclusion).
8. Participation in another investigational protocol or use of another investigational drug within 30 days of enrollment.
9. Enrollment time window has been exceeded (must be enrolled within 7 days of hospital admission and within 48 hours of development of ARDS).

10. Significant pre-existing organ dysfunction prior to randomization:

    10.1. Lung: Receiving supplemental home oxygen therapy at baseline for pre-existing medical condition (other than COVID-19), as documented in medical record. 10.2. 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. WHO Class III or IV pulmonary hypertension. 10.3. Renal: End-stage renal disease requiring renal replacement therapy or eGFR <30 mL/min. 10.4. Liver: Severe chronic liver disease defined as Child-Pugh Class C or pre-existing severe hepatic dysfunction (i.e.; portal hypertension, cirrhosis, ascites, esophageal variceal bleeding, acute hepatic necrosis). 10.5. Hematologic: Baseline platelet count <30,000/mm3 or hemoglobin levels <6.0 g/dL. 10.6. Neurological: Severe traumatic brain injury, with intracranial injury demonstrated by head CT 10.7. History of splenectomy or splenomegaly (spleen weighing > 750 g).

11. Currently receiving extracorporeal life support (ECLS/ECMO) or high-frequency oscillatory ventilation (HFOV).
12. Anticipated extubation within 24 hours of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MRG-001 (Low-dose); MRG-001 will be administered subcutaneously at 0.007 mL/kg. Patients will receive 3 injections per week every other day for a total of 2 weeks or until discharge from the ICU.	Drug: MRG-001 (Low-dose); MRG-001 is subcutaneously administered.
Experimental: MRG-001 (High-dose); MRG-001 will be administered subcutaneously at 0.01 mL/kg. Patients will receive 3 injections per week every other day for a total of 2 weeks or until discharge from the ICU.	Drug: MRG-001 (High-dose); MRG-001 is subcutaneously administered.
Placebo Comparator: Placebo; Sterile injectable saline will be administered subcutaneously at 0.01 mL/kg. Patients will receive 3 injections per week every other day for a total of 2 weeks or until discharge from the ICU.	Other: Placebo; Saline placebo will be administered subcutaneously based on bodyweight and similar dose as the treatment group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemopoietic stem cell mobilization	The primary efficacy endpoint is the absolute change of hematopoietic stem cell mobilization (CD34+ cells) calculated as cells/μl at the peak of mobilization at 12 hours compared to baseline after MRG-001 injection. degree of hematopoietic stem cell mobilization (CD34+, cells/μl) measured as a longitudinal outcome over the first 24 hours after after MRG-001 injection.	24 Hours
Organ Failure	The primary safety endpoint is organ system failure free days to day 28. Patients will be monitored daily for 28 days for signs of the failure of non-pulmonary organs and systems. The following non-pulmonary organ system failures will be assessed: circulatory, coagulation, hepatic and renal failure.	28 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Change in the trough concentration (Ctrough) of tacrolimus in ng/mL in whole blood during the course of treatment.	28 Days
Pharmacokinetics	Change in the trough concentration (Ctrough) of plerixafor in ng/mL in plasma during the course of treatment.	28 Days
Pharmacodynamics	Change in absolute numbers or percentages from baseline in circulating stem cells and immune cells measured by flow cytometry	28 Days
Cytokine Changes	Change from baseline in serum cytokines including IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IFN- γ, TNF-α.	28 Days
Respiratory-Free Days	The number of days patients in the ICU do not require supplemental forms of oxygen.	28 Days

Collaborators and Investigators

• Sponsor: MedRegen LLC
• Collaborators: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Gordon R Bernard, MD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Ahmadi AR, Atiee G, Chapman B, Reynolds L, Sun J, Cameron AM, Wesson RN, Burdick JF, Sun Z. A phase I, first-in-human study to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of MRG-001 in healthy subjects. Cell Rep Med. 2023 Sep 19;4(9):101169. doi: 10.1016/j.xcrm.2023.101169. Epub 2023 Aug 25.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 18, 2023
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 22, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Stem Cells; Acute Respiratory Distress Syndrome; Immunomodulation; MRG-001
• Additional Relevant MeSH Terms: Pathologic Processes; Respiration Disorders; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease; Infant, Newborn, Diseases; Shock; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Insufficiency; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Cytokine Release Syndrome; Respiratory Tract Diseases
• Other Study ID Numbers: MRG23ARDS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No