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

NCT06308926 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MRG23ARDS
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Acute Respiratory Distress Syndrome; Respiratory Failure; Respiratory Distress Syndrome; Respiratory Tract Diseases; Cytokine Storm

Keywords

Acute Respiratory Distress Syndrome; MRG-001; Stem Cells; Immunomodulation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Pharmacokinetics

  28 Days

• Pharmacokinetics

  28 Days

• Pharmacodynamics

  28 Days

• Cytokine Changes

  28 Days

• Respiratory-Free Days

  28 Days

Study Arms (3)

MRG-001 (Low-dose)

EXPERIMENTAL

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 (High-dose)

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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

Interventions

MRG-001 (Low-dose) DRUG

MRG-001 is subcutaneously administered.

MRG-001 (Low-dose)

MRG-001 (High-dose) DRUG

MRG-001 is subcutaneously administered.

MRG-001 (High-dose)

Placebo OTHER

Saline placebo will be administered subcutaneously based on bodyweight and similar dose as the treatment group.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• PaO2/FiO2 \< 300.
• 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.

You may not qualify if:

• Age less than 18 years.
• 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).
• Pregnancy documented or suspected in women of child bearing potential, unless ruled out by a negative pregnancy test during screening or breast feeding.
• Immunocompromised patients:
• 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).
• 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.
• Hypersensitivity to either of the components of MRG-001.
• 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.
• Participation in another investigational protocol or use of another investigational drug within 30 days of enrollment.
• Enrollment time window has been exceeded (must be enrolled within 7 days of hospital admission and within 48 hours of development of ARDS).
• 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. 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).
• Currently receiving extracorporeal life support (ECLS/ECMO) or high-frequency oscillatory ventilation (HFOV).
• Anticipated extubation within 24 hours of enrollment.

Sponsors & Collaborators

• MedRegen LLC: lead
• Vanderbilt University Medical Center: collaborator

Related Publications (1)

• 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.

  PMID: 37633275 RESULT

MeSH Terms

Conditions

Respiratory Distress Syndrome; Respiratory Insufficiency; Respiratory Tract Diseases; Cytokine Release Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiration Disorders; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Gordon R Bernard, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MedRegen LLC

CONTACT

4437598563; info@medregenco.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: March 13, 2024
• Study Start: December 1, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share