Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome

COVID Clinical Trial

— ARDS-MSC-205  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04447833
• Other study ID #: 2020-02238
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 17, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2024
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 7
• Est. completion date: June 30, 2025
• Est. primary completion date: January 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• ARDS, Human
• COVID
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• Mesenchymal Stromal Stem Cells - KI-MSC-PL-205
Allogeneic bone marrow derived mesenchymal stromal stem cells (MSCs).

Locations

Country	Name	City	State
Sweden	Uppsala University Hospital	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Uppsala University	Uppsala University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Efficacy; Hospital stay	Duration of ICU stay and hospital stay (number of days; whole hospital period + calculated from Day 1)	Day 60 post-infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Sensitisation test	Sensitisation tests (test for donor-specific antibodies) against KI-MSC-PL-205 donor	Baseline (pre-infusion), day 60 post-infusion