Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome (ARDS-MSC-205)

Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome Validation of Mechanistic Pathways and Clinical Efficacy

This is an open label, dose escalating safety study of the advanced therapy investigational medicinal product (ATIMP) KI-MSC-PL-205, where patients diagnosed with SARS-CoV-2-induced severe acute respiratory distress syndrome (ARDS), according to the Berlin Definition, and who are on respirator/ventilator (used synonymously in this protocol) support due to respiratory insufficiency with or without concomitant circulatory problems, will be included and treated with a single dose of KI-MSC-PL-205.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID; ARDS, Human
• Intervention / Treatment: Drug: Mesenchymal Stromal Stem Cells - KI-MSC-PL-205

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden, 75185
    • Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willing and able to provide written informed consent prior to performing study procedures (and have given written consent)
• Coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test at screening
• Male or female patient aged 18 to 65 years old
• Patient must fulfil the Berlin Definition of severe ARDS within 3 weeks to 48 hours prior to enrolment (Will be assessed once the patient has been admitted to the ICU)
• Patient is on respirator support within 3 weeks to 48 hours prior to enrolment (Will be assessed once the patient has been admitted to the ICU)
• Pregnancy test in blood confirming negative results before enrolment (for women ≤55 years old)

Exclusion Criteria:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study
• Patients with history of treated blood and/or solid organ malignancy with recurrence within five years prior to dosing of the ATIMP are to be excluded. Patients with history of cervix cancer and non-melanoma skin cancer with recurrence within two years prior to dosing of the ATIMP are to be excluded
• Pregnant or breast feeding female
• Patient with a history of anti-coagulation therapy for other indications that short-term prophylaxis after surgery
• Patients with a history and/ or on-going treatment for entity associated with bleeding disorder or potential risk for bleeding (e.g. inflammatory bowel disease, gastro-esophagitis with or without ulcers, haemophilia and other bleeding disorders, inflammatory musculo-skeletal disease with potential bleeding complications)
• Patients with a history during the latest five years and/or on-going treatment for systemic infection (e.g. Septicaemia due to in vivo foreign body (e.g. stents, catheters, heart valve), tuberculosis, malaria, other opportunistic and parasite infections)
• Prisoner
• Any other irreversible disease or condition for which six-month mortality is estimated to be greater than 50%
• Moderate to severe liver failure (Child-Pugh Score >12)
• Reduced renal function with a creatinine clearance (Cockcroft-Gault Equation) < 45 mL/min/1.73m2
• Severe chronic respiratory disease with a PaCO2 >50 mmHg or the use of home oxygen
• Major trauma in the prior 5 days
• Lung transplant patient
• Patients on ECMO-support
• Patients with a previous history of severe burns
• Documented deep venous thrombosis or pulmonary embolism within past three months
• Known hypersensitivity to DMSO
• Investigator considers the patient unlikely to comply with study procedures, restrictions and requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal Stromal Stem Cell Treatment; Infusion of allogeneic bone marrow derived mesenchymal stromal stem cells (MSC). First three patients receive a singe dose of 1x10^6 MSC/kg dose, next six patients receive a single dose of 2x10^6 MSC/kg.	Drug: Mesenchymal Stromal Stem Cells - KI-MSC-PL-205; Allogeneic bone marrow derived mesenchymal stromal stem cells (MSCs).; Other Names: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of pre-specified treatment related adverse events of interest (TRAEIs).	The incidence of pre-specified treatment related adverse events of interest (TRAEIs) occurring during the 10 days interval beginning with the start of the ATIMP infusion: New ventricular tachycardia, ventricular fibrillation or asystole within 10 days after infusion; New cardiac arrhythmia requiring cardioversion within 10 days after infusion; Clinical scenario consistent with transfusion incompatibility or transfusion-related infection within 10 days after infusion; Thromboembolic events (e.g. Pulmonary embolism) within 10 days after infusion; Cardiac arrest or death within 10 days after infusion	From drug administration to day 10 post-infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety; All-cause mortality	All-cause mortality at 60 days and then annually	60 days post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in Leucocytes	Changes from baseline (Day 1; prior to administration of ATIMP) in the leucocyte Count (number/L)	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in Trombocytes	Changes from baseline (Day 1; prior to administration of ATIMP) in the trombocyte Count (number/L)	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in plasma concentration of C-reactive protein (CRP)	Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of CRP (mg/L)	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in plasma concentration of Prothrombin complex (PK)	Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of PK (INR)	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in plasma concentration of Creatinine	Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of creatinine (μmol/L)	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in plasma concentration of Aspartate amino transferase (ASAT)	Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ASAT (μkat/L)	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in plasma concentration of Alanine amino transferase (ALAT)	Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ALAT (μkat/L)	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP)	Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of NT-proBNP (ng/L)	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in Blood pressure	Changes from baseline (Day 1; prior to administration of ATIMP) in blood pressure (mmHg)	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in Body temperature	Changes from baseline (Day 1; prior to administration of ATIMP) in body temperature (°C)	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Efficacy; Changes in pulmonary compliance	Changes from baseline (Day 1; prior to administration of ATIMP) in pulmonary compliance (dynamic and static) until day 10 post-infusion	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
Efficacy; Changes in driving pressure (Plateau pressure- PEEP)	Changes from baseline (Day 1; prior to administration of ATIMP) in driving pressure (Plateau pressure- PEEP) until day 10 post-infusion	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
Efficacy; Changes in oxygenation (PaO2/FiO2)	Changes from baseline (Day 1; prior to administration of ATIMP) in oxygenation (PaO2/FiO2) until day 10 post-infusion	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
Efficacy; Duration of ventilator support	Number of days with ventilator support	Baseline (pre-infusion),day 1, 2, 3, 4, 7, 10 and 60 post-infusion
Efficacy; Pulmonary bilateral infiltrates	Changes in amount of pulmonary bilateral infiltrates assessed by pulmonary X-ray from baseline (Day 1; prior to administration of ATIMP) until day 60	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Efficacy; Sequential Organ Failure Assessment (SOFA) score	Changes in Sequential Organ Failure Assessment (SOFA) score from baseline (Day 1; prior to administration of ATIMP) and during the ICU-period	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, end of ICU
Efficacy; Hospital stay	Duration of ICU stay and hospital stay (number of days; whole hospital period + calculated from Day 1)	Day 60 post-infusion
Lung function	Recovery of lung function assessed by Spirometry (FEV1, Vital Capacity) at day 60 and then annually	Day 60 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Lung fibrosis	To assess development of lung fibrosis using the HRCT Fibrosis Score using Computed tomography (CT) at baseline and on day 1, 3, 7, 10, end of ICU-residence, end of hospital stay, day 60, 6 month and 12 month and end of study (if possible during the infectious stage depending on hospital safety regimen during the pandemic).	Baseline (pre-infusion), day 1, 3, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Six minutes walk test	Assessment of the patient's physical capacity by 6-Minute-Walk-Test (6MWT), starting at 6 months post Day 1 and then annually	6 months, 1, 2, 3, 4 and 5 years post-infusion
Changes in Quality of life	Changes in Quality of Life by assessing the Short Form Health Survey (SF-36) score (starting at 6 months post Day 1 and then annually; patient reported outcome)	6 months, 1, 2, 3, 4 and 5 years post-infusion
Blood biomarkers	Change in blood biomarkers related to the proposed mechanisms of action of KI-MSC-PL-205 in ARDS	Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
Sensitisation test	Sensitisation tests (test for donor-specific antibodies) against KI-MSC-PL-205 donor	Baseline (pre-infusion), day 60 post-infusion

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: Uppsala University Hospital
• Investigators: Principal Investigator: Oscar Simonsson, MD, PhD, Uppsala University

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2020
• Primary Completion (Actual): January 30, 2021
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: June 20, 2020
• First Submitted That Met QC Criteria: June 24, 2020
• First Posted (Actual): June 25, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Mesenchymal Stromal Stem Cells
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 2020-02238

Drug and device information, study documents

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