Clinical trial NCT06308926: MRG-001 as an Immunoregulatory and Regenerative Therapy for ARDS Patients
Official title: A Phase IIa, Double-Blind, Randomized, Multi-Center Study Comparing MRG-001 to Placebo in Patients With Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
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
Lead sponsor: MedRegen LLC
Sponsor class: INDUSTRY
Collaborators: name: Vanderbilt University Medical Center
First posted: 2024-03-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Hemopoietic stem cell mobilization
timeFrame: 24 Hours
measure: Organ Failure
timeFrame: 28 Days
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: 28 Days
measure: Pharmacokinetics
timeFrame: 28 Days
measure: Pharmacodynamics
timeFrame: 28 Days
measure: Cytokine Changes
timeFrame: 28 Days
measure: Respiratory-Free Days
timeFrame: 28 Days
Other outcomes:
Locations:
Study officials:
affiliation: Vanderbilt University Medical Center
name: Gordon R Bernard, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.