| Eligibility |
Inclusion Criteria:
1. Subjects =18 to =80 years of age with a diagnosis of moderate or severe COVID-19, with
or without pneumonia, as follows:
1. SARS-CoV-2 infection, as confirmed by RT-PCR test within 72 hours before dosing.
2. Subjects hospitalised primarily due to COVID-19, with symptoms considered typical
for COVID-19 (eg, fever, cough, sore throat, malaise, headache, muscle pain,
gastrointestinal symptoms, shortness of breath, or dyspnoea requiring oxygen
treatment).
3. A score of 4, 5, or 6 on the NIAID 8-point ordinal scale for COVID-19 severity,
as follows (Beigel et al 2020, Appendix II):
i. Score 4: Hospitalised, not requiring supplemental oxygen, but requiring ongoing
medical care (related to COVID-19 or to other medical conditions). ii. Score 5:
Hospitalised, requiring any supplemental oxygen. iii. Score 6: Hospitalised, requiring
non-invasive ventilation or use of high-flow oxygen devices.
2. Willing and able to give written informed consent prior to the initiation of any trial
procedure.
3. For females only: At the time of enrolment, negative beta human chorionic gonadotropin
(ß-hCG) pregnancy test (serum) for women of childbearing potential (WOCBP). A woman
will be considered WOCBP following menarche and until becoming postmenopausal unless
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral
salpingectomy, and bilateral oophorectomy.
A postmenopausal state is defined as no menses for 12 months without an alternative
medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal
range may be used to confirm a postmenopausal state in women not using hormonal
contraception or hormonal replacement therapy. However, in the absence of 12 months of
amenorrhea, a single FSH measurement is insufficient.
4. If the subject is a WOCBP, must agree to practice highly effective method of
contraception from screening visit and until 30 days after the last investigational
medicinal product (IMP) administration. Highly effective methods of contraception
include: a. Combined (estrogen- and progestogen-containing) hormonal contraception
associated with inhibition of ovulation: i. Oral ii. Intravaginal iii. Transdermal b.
Progestogen-only hormonal contraception associated with inhibition of ovulation: i.
Oral ii. Injectable iii. Implantable c. Intrauterine devices d. Intrauterine
hormone-releasing system e. Bilateral tubal occlusion f. Vasectomized partner g.
Sexual abstinence (defined as refraining from heterosexual intercourse during the
entire period of risk associated with the trial treatments. The reliability of sexual
abstinence needs to be evaluated in relation to the preferred and usual lifestyle of
the subject) Note: Methods that can achieve a failure rate of less than 1% per year
when used consistently and correctly are considered as highly effective contraceptive
methods.
Exclusion Criteria:
1. Is currently participating or has participated in a study of an investigational agent
or has used an investigational device within 4 weeks prior to the first dose of study
treatment in this trial (subjects who are in a follow-up period of an investigational
study may participate as long as it has been 4 weeks after the last dose of the
previous investigational agent).
2. Life expectancy <72 hours, in the opinion of the Investigator.
3. Subjects requiring invasive mechanical ventilation or ECMO.
4. Subjects on non-invasive CPAP ventilation or HFNO (score 6 of the NIAID 8-point
ordinal scale for COVID-19 severity; Beigel et al 2020, Appendix II) are allowed, but
will be excluded if they have moderate to severe ARDS (eg, same day ratio of arterial
partial pressure of oxygen to fraction of inspired oxygen [PaO2/FiO2] =200 mmHg; or
oxygen saturation [SpO2]/FiO2 =232 if arterial blood gas test is not available).
5. Active known cancer disease, except subjects with nonaggressive cancers such as basal
cell carcinoma, or cervical carcinoma in situ.
6. Clinical evidence of active infection, in addition to the SARS-CoV-2 infection,
including influenza.
7. Body weight >120 kg.
8. Pregnant or breastfeeding female subject.
9. Alzheimer's disease or dementia or any other medical condition that, in the opinion of
the investigator, impact the subject's capability to properly consent with trial
participation or to comply with trial protocol procedures.
10. Signs of disseminated intravascular coagulation as per the investigator's medical
judgement based on the symptoms of the subject, such as unexplained bleeding, along
with subject's laboratory parameters including platelet count, prothrombin
time-international normalised ratio (PT-INR), partial thromboplastin time (PTT),
plasma fibrinogen, and plasma D-dimer.
11. Creatinine clearance <30 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) equations.
12. Abnormal liver chemistry, defined as ALT or aspartate aminotransferase (AST) or total
bilirubin or PT-INR >1.5 × upper limit of normal (ULN).
13. Severe cardiovascular diseases (severe or unstable angina, congestive heart failure
(New York Heart Association [NYHA] III-IV), myocardial infarction within past 1 year,
uncontrolled hypertension, and uncontrolled arrhythmia).
14. Electrocardiogram (ECG) findings with corrected QT interval using Fridericia's (QTcF)
formula >500 msec.
15. Subjects with a known or suspected hypersensitivity to MSCs or contaminants (DMSO and
Accutase).
16. COVID-19 vaccine administered within less than 14 days prior to screening.
17. Known thrombosis or thromboembolic event (TEE) or known medical history of TEEs (eg,
cerebrovascular accidents, transient ischemic attack, myocardial infarction, pulmonary
embolism, and deep vein thrombosis) within the previous 3 months or those subjects
particularly at risk for TEEs (eg, history of thrombophilia, permanent immobilisation,
or permanent paralysis of their lower extremities).
18. Any other medical condition which, in the opinion of the investigator, would impact
the safety of the subject or interfere with the subject's ability to comply with the
trial and follow-up procedures.
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