Mesenchymal Stem Cells for The Treatment of Acute Respiratory Distress Syndrome (ARDS)

• ClinicalTrials.gov Identifier: NCT04347967
• Recruitment Status: Not yet recruiting
• First Posted: April 15, 2020
• Last Update Posted: March 20, 2023
• Sponsor: Meridigen Biotech Co., Ltd.
• Information provided by (Responsible Party): Meridigen Biotech Co., Ltd.

Tracking Information

• First Submitted Date: April 12, 2020
• First Posted Date: April 15, 2020
• Last Update Posted Date: March 20, 2023
• Estimated Study Start Date: September 2023
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 12, 2020)

The incidence and frequency of adverse events related to administration of UMC119-06. [ Time Frame: 3 months from the day of administration ]

Incidence of Treatment-Emergent Adverse Events (TEAEs). Incidence of withdrawals due to AEs.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 14, 2021)

• Changes in mortality status [ Time Frame: 15 months from the day of administration. ]
  Improvement in mortality status.
• Ventilator Free Days (VFD) [ Time Frame: 28 days from the day of administration ]
  Improvement in clinical function as assessed by Ventilator Free Days (VFD).
• Change in Oxygenation Index (OI) [ Time Frame: 7 days or discharge from ICU after the day of administration ]
  Improvement in clinical function as assessed by change in Oxygenation Index (OI).
• Change in Lung Injury Score (LIS) [ Time Frame: 7 days or discharge from ICU after the day of administration ]
  Improvement in clinical function as assessed by change in Lung Injury Score (LIS), 0-16 points, severity increasing with higher points.
• Change in positive end-expiratory pressure (PEEP) [ Time Frame: 7 days or discharge from ICU after the day of administration ]
  Improvement in clinical function as assessed by change in positive end-expiratory pressure (PEEP).
• Change in Lung Static Compliance [ Time Frame: 7 days or discharge from ICU after the day of administration ]
  Improvement in clinical function as assessed by change in Lung Static Compliance
• Change in acute physiology and chronic health evaluation score (APACHE II) [ Time Frame: 7 days from the day of administration ]
  Improvement in clinical function as assessed by change in acute physiology and chronic health evaluation score (APACHE II), higher scores correspond to more severe disease and a higher risk of death.

Original Secondary Outcome Measures (submitted: April 12, 2020)

• Changes in mortality status [ Time Frame: 15 months from the day of administration. ]
  Improvement in mortality status.
• Ventilator Free Days (VFD) [ Time Frame: 28 days from the day of administration ]
  Improvement in clinical function as assessed by Ventilator Free Days (VFD).
• Change in Oxygenation Index (OI) [ Time Frame: 7 days or discharge from ICU after the day of administration ]
  Improvement in clinical function as assessed by change in Oxygenation Index (OI).
• Change in Lung Injury Score (LIS) [ Time Frame: 7 days or discharge from ICU after the day of administration ]
  Improvement in clinical function as assessed by change in Lung Injury Score (LIS)
• Change in positive end-expiratory pressure (PEEP) [ Time Frame: 7 days or discharge from ICU after the day of administration ]
  Improvement in clinical function as assessed by change in positive end-expiratory pressure (PEEP).
• Change in Lung Static Compliance [ Time Frame: 7 days or discharge from ICU after the day of administration ]
  Improvement in clinical function as assessed by change in Lung Static Compliance
• Change in acute physiology and chronic health evaluation score (APACHE II) [ Time Frame: 7 days from the day of administration ]
  Improvement in clinical function as assessed by change in acute physiology and chronic health evaluation score (APACHE II).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Mesenchymal Stem Cells for The Treatment of Acute Respiratory Distress Syndrome (ARDS)
• Official Title: The Safety and Tolerability After Intravenous Infusion of UMC119-06 in Subjects With Acute Respiratory Distress Syndrome (ARDS).
• Brief Summary: The clinical study with UMC119-06 is designed to investigate the safety in patients with moderate acute respiratory distress syndrome ("ARDS"). This will be a dose escalation, open-label, single-center study in adult with ARDS. UMC119-06 is ex vivo cultured human umbilical cord derived mensenchymal stem cells (hUC-MSCs) product which is intended for treatment of ARDS.

Detailed Description

ARDS, a noncardiogenic respiratory disease, is characterized by progressive hypoxemia and respiratory distress, associated with explosive acute inflammation and alveolar edema. ARDS occurs in all age group of patients, where mortality rates increase in advancing age.

In animal studies of ARDS, mensenchymal stem cells (MSCs) can attenuate lipopolysaccharides (LPS)-induced lung injury and pulmonary permeability edema through modulating the inflammatory. These findings show that MSCs may improve the clinical outcomes and prognosis of ARDS patient. Meridigen is developing UMC119-06, human umbilical cord-derived MSCs, for the treatment of ARDS. The purpose of this study is to assess the safety of UMC119-06 in patients with ARDS.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Respiratory Distress Syndrome

Intervention

Biological: UMC119-06

Cohort 1: Low does of UMC119-06；Cohort 2: Medium does of UMC119- 06；Cohort 3: High does of UMC119-06

Study Arms

Experimental: UMC119-06

Human Umbilical Cord Derived-Mesenchymal Stem Cells, Single treatment by intravenous infusion.

Intervention: Biological: UMC119-06

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 12, 2020): 18
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2025
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects of age ≥ 20 years and ≤ 85 years.

• Subject has a diagnosis of moderate ARDS according to the Berlin definition of ARDS:

  1. No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.
  2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph.
  3. Hypoxemia: PaO2/ FiO2 > 100 mmHg to ≤ 200 mmHg with PEEP ≥ 5 cm H2O.
  4. The time of onset of ARDS is when all of the specified ARDS criteria (2a-c) are met.
• Patient is intubated and mechanically ventilated.
• Subjects who had an onset of ARDS within 72 to 120 hours before start of treatment.
• Subjects with body weight between 40 to 90 kg.
• No decompensated heart failure.
• Subject is willing to provide written informed consent to participate in the study after reading the informed consent form and the information provided.

• Women of child-bearing potential should have a negative serum pregnancy test prior to administration of investigational product., UNLESS they meet the following criteria:

  1. Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40 mIU/ml, OR;
  2. 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy.

Exclusion Criteria:

• Greater than 72 hours since first meeting ARDS criteria per the Berlin definition.
• No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol.
• Expected life < 3 months from other cause than the respiratory failure.
• Subject is receiving extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support.
• Subjects with history of any type of malignancy.
• Major trauma in the prior 5 days.
• Subjects with major surgery (body organs that require anesthesia, such as tumor removal, open chest, heart surgery, abdominal surgery, intracranial surgery, or normal surgery for more than 3 hours, etc.) within previous 14 days.
• Subjects who are pregnant (or plan to become pregnant within 3 months of investigational product treatment) or lactating.
• Subjects who have a significant concomitant illness as judged by principal investigator (PI).

• Subjects who have significant abnormal laboratory tests at screening:

  1. >5 × upper limit of normal for alanine aminotransferase (ALT) or aspartate aminotransferase (AST).
  2. >3 × upper limit of normal for total bilirubin.
  3. >2 × upper limit of normal for serum creatinine.
• Subjects with known human immunodeficiency virus infection or who are immune compromised.
• Subjects who are unable to return for follow-up visits for clinical evaluation, laboratory studies, or imaging evaluation.
• Subjects with a history of severe allergic or anaphylactic reactions.
• Subjects with known allergy or hypersensitivity to any component of the formulation (normal saline and human serum albumin).
• Subjects who have participated in another clinical study of new investigational therapies or have received an investigational therapy within the 12 weeks before study drug administration.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Mandy Li; +886-2-2627-5175 ext 19933; Mandy.Li@meridigen.com

Contact: Katherine Huang; +886-2-2627-5175 ext 19926; Katherine.Huang@meridigen.com

• Listed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT04347967
• Other Study ID Numbers: UMC119-06-ARDS-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Meridigen Biotech Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Meridigen Biotech Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Meridigen Biotech Co., Ltd.
• Verification Date: March 2023