Clinical trial NCT04896853: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: COVID-19 Acute Respiratory Distress Syndrome
Influenza A
Metapneumovirus Pneumonia
Respiratory Syncytial Virus (RSV)
Lead sponsor: NextCell Pharma Ab
Sponsor class: INDUSTRY
Collaborators: name: Karolinska Trial Alliance
First posted: 2021-05-21
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open, dose escalating Phase IB Clinical Trial
Primary purpose: TREATMENT

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.

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

    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 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.

Primary outcomes:
measure: Safety and tolerance of a single infusion of ProTrans®
timeFrame: 24 months
Secondary outcomes:
measure: Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 7
timeFrame: 7 days
measure: Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 15
timeFrame: 15 days
measure: Effect of ProTrans® -MSC on patient clinical status, including mortality, at day 30
timeFrame: 30 days
measure: Time to clinical improvement after ProTrans® - MSC infusion
timeFrame: 30 days
measure: Effect of of ProTrans® -MSC on lung damage
timeFrame: Up to 60 days
measure: Duration of hospitalization and Intensive Care Unit (ICU) stay
timeFrame: Up to 60 days
measure: Kinetics of COVID-19, Influenza A, Metapneumovirus, Respiratory Syncytial Virus (RSV) viral load after ProTrans® -MSC infusion
timeFrame: Up to 30 days
measure: Evolution of biological markers of liver, myocardium and inflammation
timeFrame: Up to 24 months
measure: Tolerance of allogeneic Wharton's jelly (WJ) Mesenchymal Stromal Cells (ProTrans®) for severe COVID-19, Influenza A, Metapneumovirus or RSV respiratory conditions
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Örebro
country: Sweden
facility: Department of Cardiology, Respiratory medicine and Physiology, Örebro University Hospital
Study officials:
affiliation: NextCell Pharma
name: Mathias Svahn, PhD
role: STUDY_CHAIR
affiliation: Department of Cardiology, Respiratory medicine and Physiology, Örebro University Hospital
name: Josefine Sundh, MD
role: PRINCIPAL_INVESTIGATOR
References: