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Treatment of Respiratory Complications Associated With COVID19,Influenza ,Metapneumovirus,RSV Infection Using ProTrans®

Primary Purpose

COVID-19 Acute Respiratory Distress Syndrome, Influenza A, Metapneumovirus Pneumonia

Status
Recruiting
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
ProTrans®
Sponsored by
NextCell Pharma Ab
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 Acute Respiratory Distress Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Male or female, aged 18 - 75 years old
  • Has laboratory-confirmed SARS-CoV-2 infection as determined by reverse-transcription polymerase chain reaction (RT-PCR) in any specimen prior to inclusion.
  • Hospitalized patients not previously admitted due to COVID-19 infection
  • Patients classified as severe pneumonia, as defined by the need for continuous supplemental oxygen 5 L/min 02 OR high flow oxygen, 50% Fraction of Inspired Oxyge (FiO2) ≥ 30 l/min and cannot saturate > 96% not under "non-invasive" ventilation nor invasive mechanical ventilation nor ECMO
  • Women of childbearing potential must agree to use contraception or acceptable birth control for the duration of the study.

Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1:

  • oral
  • intravaginal
  • transdermal, progestogen-only hormonal contraception associated with inhibition of ovulation 1:
  • oral
  • injectable
  • implantable 2; intrauterine device (IUD) 2, intrauterine hormone-releasing system (IUS) 2, bilateral tubal occlusion 2, vasectomised partner 2,3, sexual abstinence 4

    1. Hormonal contraception may be susceptible to interaction with the Investigational Medicinal Products (IMP), which may reduce the efficacy of the contraception method
    2. Contraception methods that in the context of this guidance are considered to have low user dependency.
    3. Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success. 4 In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.

      • Provision of a written informed consent

Exclusion Criteria:

  • Inability to provide informed consent
  • Patients not expected to survive for 24 hours or mechanically ventilated at inclusion or previously during present hospitalization
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin (hCG) laboratory test
  • Patients with weight > 100 kg or weight < 50 kg
  • Patients with known, or previous, malignancy
  • Patients with other serious systemic diseases deemed of contra-indication by the physician
  • Patient with any of following laboratory results out of the ranges detailed below at screening: Absolute neutrophil count (ANC) ≤ 1.0 x 10e9/L, Platelets (PLT) < 50 10e9 /L, ASAT or ALAT > 5N, estimated glomerular filtration rate (eGFR) < 30 mL/min
  • Current documented bacterial infection
  • Serological evidence of infection with human immunodeficiency virus, Treponema pallidum, hepatitis B antigen (serology consistent with previous vaccination and a history of vaccination is acceptable) or hepatitis C
  • Latent or previous as well as on-going therapy against tuberculosis, or exposed to tuberculosis or have travelled in areas with high risk of tuberculosis or mycosis within the last 3 months
  • Patients with known allergies to a component of the ProTrans® product
  • Ongoing treatment with Remdesivir
  • Pre-existing chronic respiratory diseases requiring long- term oxygen therapy
  • Pre-existing cirrhosis with basal Child and Pugh of C
  • Patients with history of increased risk for thrombo- embolic and/or co-morbidity for thrombo- embolism
  • Patients with a history of myocardium infarction
  • A history of cardiac dysfunction, as assessed as:

Clinical sign of a congestive heart failure refractory; Left ventricular ejection fraction <35% at myocardial scintigraphy or echocardiography; Pulmonary arterial hypertension with systolic pulmonary artery pressure (PAP) at echography > 40 mmHg Chronic atrial fibrillation requiring oral anticoagulant therapy; Uncontrolled ventricular arrhythmia; Pericardial effusion with hemodynamic compromise assessed by echocardiography.

Sites / Locations

  • Department of Cardiology, Respiratory medicine and Physiology, Örebro University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Wharton's Jelly (WJ)-Umbilical Cord (UC) Mesenchymal Stromal Cells (ProTrans®).Study patients 1-3 will receive a single dose of 25 million cells, patients 4-6 will receive 100 million cells and patients 7-9 will receive 200 million cells.

Outcomes

Primary Outcome Measures

Safety and tolerance of a single infusion of ProTrans®
Grade 3 or 4 adverse event but not usual in natural course of the disease.
Effect of ProTrans® -MSC on patient clinical status, including mortality
The rate of use of mechanical ventilation (necessitating intubation) or death.

Secondary Outcome Measures

Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 7
Effect of ProTrans® -MSC on patient clinical status assessed on the 7-point ordinal scale; 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO) 7. Death.
Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 15
Effect of ProTrans® -MSC on patient clinical status assessed on the 7-point ordinal scale; 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or ECMO 7. Death.
Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 30
Effect of ProTrans® -MSC on patient clinical status assessed on the 7-point ordinal scale; 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or ECMO 7. Death.
Time to clinical improvement after ProTrans® - MSC infusion
Time to clinical improvement of one category from admission on the 7-point ordinal scale after ProTrans® - MSC infusion
Effect of of ProTrans® -MSC on lung damage
Lung damage using imaging techniques (Chest X ray/CT scan /or on doppler ultrasound) when assessed for clinical need up to hospital discharge X ray/CT scan /or on doppler ultrasound) when assessed for clinical need
Duration of hospitalization and Intensive Care Unit (ICU) stay
Duration of hospitalization and ICU stay
Kinetics of COVID-19, Influenza A, Metapneumovirus, Respiratory Syncytial Virus (RSV) viral load after ProTrans® -MSC infusion
Quantitative PCR for SARS-CoV, Influenza A, Metapneumovirus, Respiratory Syncytial Virus (RSV) virus in throat swabs (time frame: before MSC infusion on Day 0 and after MSC infusion on day 30)

Full Information

First Posted
May 18, 2021
Last Updated
March 31, 2023
Sponsor
NextCell Pharma Ab
Collaborators
Karolinska Trial Alliance
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1. Study Identification

Unique Protocol Identification Number
NCT04896853
Brief Title
Treatment of Respiratory Complications Associated With COVID19,Influenza ,Metapneumovirus,RSV Infection Using ProTrans®
Official Title
Treatment of Respiratory Complications Associated With COVID-19, Influenza A, Metapneumovirus, Respiratory Syncytial Virus Infection Using Wharton's Jelly-Umbilical Cord Mesenchymal Stromal Cells (ProTrans®): Open Phase IB Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 18, 2021 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NextCell Pharma Ab
Collaborators
Karolinska Trial Alliance

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To investigate the safety and tolerance of a single infusion of ProTrans® in subjects with "severe" respiratory complications associated with pneumonia caused by COVID-19, Influenza A, Metapneumovirus or RSV infection.
Detailed Description
The investigators hypothesize that the systemic delivery of WJ-MSCs exerts an anti-inflammatory action and anti-apoptotic effect in the lung of COVID-19, Influenza A, Metapneumovirus or RSV patients. The nature of these cells to immunomodulate both tissue resident and bloodborne immune cells towards a more anti-inflammatory and tolerogenic profile, results in a reduction of tissue-based inflammation within the lung and triggering of repair responses. This clinically culminates in a beneficial action on patients with "severe" respiratory complications associated with pneumonia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Acute Respiratory Distress Syndrome, Influenza A, Metapneumovirus Pneumonia, Respiratory Syncytial Virus (RSV)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
This is an open, dose escalating Phase IB Clinical Trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
Wharton's Jelly (WJ)-Umbilical Cord (UC) Mesenchymal Stromal Cells (ProTrans®).Study patients 1-3 will receive a single dose of 25 million cells, patients 4-6 will receive 100 million cells and patients 7-9 will receive 200 million cells.
Intervention Type
Biological
Intervention Name(s)
ProTrans®
Intervention Description
Allogeneic Wharton's jelly (WJ) Mesenchymal Stromal Cells
Primary Outcome Measure Information:
Title
Safety and tolerance of a single infusion of ProTrans®
Description
Grade 3 or 4 adverse event but not usual in natural course of the disease.
Time Frame
24 months
Title
Effect of ProTrans® -MSC on patient clinical status, including mortality
Description
The rate of use of mechanical ventilation (necessitating intubation) or death.
Time Frame
15 days
Secondary Outcome Measure Information:
Title
Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 7
Description
Effect of ProTrans® -MSC on patient clinical status assessed on the 7-point ordinal scale; 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO) 7. Death.
Time Frame
7 days
Title
Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 15
Description
Effect of ProTrans® -MSC on patient clinical status assessed on the 7-point ordinal scale; 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or ECMO 7. Death.
Time Frame
15 days
Title
Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 30
Description
Effect of ProTrans® -MSC on patient clinical status assessed on the 7-point ordinal scale; 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or ECMO 7. Death.
Time Frame
30 days
Title
Time to clinical improvement after ProTrans® - MSC infusion
Description
Time to clinical improvement of one category from admission on the 7-point ordinal scale after ProTrans® - MSC infusion
Time Frame
30 days
Title
Effect of of ProTrans® -MSC on lung damage
Description
Lung damage using imaging techniques (Chest X ray/CT scan /or on doppler ultrasound) when assessed for clinical need up to hospital discharge X ray/CT scan /or on doppler ultrasound) when assessed for clinical need
Time Frame
Up to 60 days
Title
Duration of hospitalization and Intensive Care Unit (ICU) stay
Description
Duration of hospitalization and ICU stay
Time Frame
Up to 60 days
Title
Kinetics of COVID-19, Influenza A, Metapneumovirus, Respiratory Syncytial Virus (RSV) viral load after ProTrans® -MSC infusion
Description
Quantitative PCR for SARS-CoV, Influenza A, Metapneumovirus, Respiratory Syncytial Virus (RSV) virus in throat swabs (time frame: before MSC infusion on Day 0 and after MSC infusion on day 30)
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female, aged ≥18 years old Has laboratory-confirmed SARS-CoV-2, Influenza A, Metapneumovirus or RSV infection as determined by reverse-transcription polymerase chain reaction (RT-PCR) in any specimen prior to inclusion. Hospitalized patients. Patients classified as severe pneumonia, as defined by the need for continuous supplemental oxygen 5 L/min 02 OR high flow oxygen, 35% FiO2 > 30l/min and cannot saturate > 96% NOT under "non-invasive" ventilation NOR invasive mechanical ventilation NOR ECMO. Women of childbearing potential must agree to use contraception or acceptable birth control for the duration of the study. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1: oral intravaginal transdermal, progestogen-only hormonal contraception associated with inhibition of ovulation 1: oral injectable implantable 2; intrauterine device (IUD) 2, intrauterine hormone-releasing system (IUS) 2, bilateral tubal occlusion 2, vasectomised partner 2,3, sexual abstinence 4 Hormonal contraception may be susceptible to interaction with the Investigational Medicinal Products (IMP), which may reduce the efficacy of the contraception method Contraception methods that in the context of this guidance are considered to have low user dependency. Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success. 4 In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Provision of a written informed consent Exclusion Criteria: Inability to provide informed consent Patients not expected to survive for 24 hours or mechanically ventilated at inclusion or previously during present hospitalization Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin (hCG) laboratory test Patients with BMI ≥30 Patients with known, or previous, malignancy Patients with other serious systemic diseases deemed of contra-indication by the physician Patient with any of following laboratory results out of the ranges detailed below at screening: Absolute neutrophil count (ANC) ≤ 1.0 x 10e9/L, Platelets (PLT) < 50 10e9 /L, ASAT or ALAT > 5N, estimated glomerular filtration rate (eGFR) < 30 mL/min Current documented bacterial infection Serological evidence of infection with human immunodeficiency virus, Treponema pallidum, hepatitis B antigen (serology consistent with previous vaccination and a history of vaccination is acceptable) or hepatitis C Latent or previous as well as on-going therapy against tuberculosis, or exposed to tuberculosis or have travelled in areas with high risk of tuberculosis or mycosis within the last 3 months Patients with known allergies to a component of the ProTrans® product Ongoing treatment with Remdesivir Pre-existing chronic respiratory diseases requiring long- term oxygen therapy Pre-existing cirrhosis with basal Child and Pugh of C Patients with history of increased risk for thrombo- embolic and/or co-morbidity for thrombo- embolism Patients with a history of myocardium infarction A history of cardiac dysfunction, as assessed as: Clinical sign of a congestive heart failure refractory; Left ventricular ejection fraction <35% at myocardial scintigraphy or echocardiography; Pulmonary arterial hypertension with systolic pulmonary artery pressure (PAP) at echography > 40 mmHg Chronic atrial fibrillation requiring oral anticoagulant therapy; Uncontrolled ventricular arrhythmia; Pericardial effusion with hemodynamic compromise assessed by echocardiography.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mathias Svahn, PhD
Phone
+46 (0)70 2615504
Email
mathias.svahn@nextcellpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mathias Svahn, PhD
Organizational Affiliation
NextCell Pharma
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Josefine Sundh, MD
Organizational Affiliation
Department of Cardiology, Respiratory medicine and Physiology, Örebro University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Cardiology, Respiratory medicine and Physiology, Örebro University Hospital
City
Örebro
ZIP/Postal Code
701 85
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Josefin Sundh, MD
Email
Josefin.sundh@regionorebrolan.se

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Treatment of Respiratory Complications Associated With COVID19,Influenza ,Metapneumovirus,RSV Infection Using ProTrans®

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