Clinical trial NCT04447833: Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome
Official title: Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome Validation of Mechanistic Pathways and Clinical Efficacy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: ARDS, Human
COVID
Keywords: Mesenchymal Stromal Stem Cells
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Uppsala University Hospital
First posted: 2020-06-25
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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).
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: The incidence of pre-specified treatment related adverse events of interest (TRAEIs).
timeFrame: From drug administration to day 10 post-infusion
Secondary outcomes:
measure: Safety; All-cause mortality
timeFrame: 60 days post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in Leucocytes
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in Trombocytes
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in plasma concentration of C-reactive protein (CRP)
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in plasma concentration of Prothrombin complex (PK)
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in plasma concentration of Creatinine
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in plasma concentration of Aspartate amino transferase (ASAT)
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in plasma concentration of Alanine amino transferase (ALAT)
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP)
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in Blood pressure
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in Body temperature
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Efficacy; Changes in pulmonary compliance
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
measure: Efficacy; Changes in driving pressure (Plateau pressure- PEEP)
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
measure: Efficacy; Changes in oxygenation (PaO2/FiO2)
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion
measure: Efficacy; Duration of ventilator support
timeFrame: Baseline (pre-infusion),day 1, 2, 3, 4, 7, 10 and 60 post-infusion
measure: Efficacy; Pulmonary bilateral infiltrates
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Efficacy; Sequential Organ Failure Assessment (SOFA) score
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, end of ICU
measure: Efficacy; Hospital stay
timeFrame: Day 60 post-infusion
measure: Lung function
timeFrame: Day 60 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Lung fibrosis
timeFrame: Baseline (pre-infusion), day 1, 3, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Six minutes walk test
timeFrame: 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Changes in Quality of life
timeFrame: 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Blood biomarkers
timeFrame: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion
measure: Sensitisation test
timeFrame: Baseline (pre-infusion), day 60 post-infusion
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: Uppsala University
name: Oscar Simonsson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: