| Eligibility |
Inclusion Criteria:
1. Subject (or legally authorized representative) provides informed consent prior to
initiation of any study procedures.
2. Subject (or legally authorized representative) understands and agrees to comply with
planned study procedures.
3. Male and non-pregnant female subjects with age =18 years of age at the time of
randomization.
4. Admitted to a hospital with symptoms suggestive of severe COVID-19.
5. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial
or public health assay (including rapid antigen test) in any specimen, as documented
by either of the following:
- PCR positive in sample collected < 72 hours prior to randomization; OR
- PCR positive in sample collected = 72 hours prior to randomization, documented
inability to obtain a repeat sample (e.g. due to lack of testing supplies,
limited testing capacity, results taking > 24 hours, etc) AND progressive disease
suggestive of ongoing SARS-CoV-2 infection.
6. Illness of any duration, and at least one of the following:
- Shortness of breath, RR=30 /minute
- Clinical signs indicative of progressive aggravation, lung radiographic
infiltrates by imaging (chest x-ray, CT scan, etc.) showing >50% progression
within 24-48 hours
- PaO2/FiO=300mmHg 1mmHg=0.133kPa
- Resting state SpO2 = 93% on room air
7. All women of childbearing potential defined as any female who has experienced menarche
and who has not undergone surgical sterilization (hysterectomy or bilateral
oophorectomy) and is not postmenopausal. Highly effective contraception methods
include:
- Total Abstinence (when this is in line with the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception, or
- Use of one of the following combinations (a+b or a+c or b+c):
1. Use of oral, injected or implanted hormonal methods of contraception or
other forms of hormonal contraception that have comparable efficacy (failure
rate < 1%), for example hormone vaginal ring or transdermal hormone
contraception.
2. Placement of an intrauterine device (IUD) or intrauterine system (IUS);
3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
suppository;
- Female sterilization (have had prior surgical bilateral oophorectomy with or
without hysterectomy) or tubal ligation at least six weeks before taking study
treatment. In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow-up hormone level assessment;
- Male sterilization (at least 6 months prior to screening). For female subjects on
the study, the vasectomized male partner should be the sole partner for that
subject;
- In case of use of oral contraception women should have been stable for a minimum
of 3 months before taking study treatment. Women are considered post-menopausal
and not of childbearing potential if they have had 12 months of natural
(spontaneous) amenorrhea with an appropriate clinical profile (e.g. age
appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks
ago. In the case of oophorectomy alone, only when the reproductive status of the
woman has been confirmed by follow up hormone level assessment, is she considered
not of childbearing potential;
8. Regardless of their fertility status, male subjects must agree to either remain
abstinent (if this is their preferred and usual lifestyle) or use condoms as well as
one additional highly effective method of contraception (less than 1% failure rate) or
effective method of contraception with nonpregnant women of childbearing potential
partners for the duration of the study and until 90 days after the last dose. A condom
is required to be used also by vasectomized men in order to prevent delivery of the
drug via seminal fluid.
9. Agree not to participate in another clinical trial for the treatment of COVID-19
through Day 60 after first dose.
Exclusion Criteria:
Subjects are excluded from the study if any of the following criteria apply:
1. ALT/AST > 3 times the upper limit of normal.
2. Serum total bilirubin > 1.5 x ULN (upper limit of normal)
3. Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving
hemodialysis or hemofiltration).
4. Subjects with significant cardiovascular disease as following:
i. heart failure NYHA class =3 ii. left ventricular ejection fraction <50% iii. those
with a history of cardiac arrhythmias, including long QT syndrome.
5. Neutropenia (absolute neutrophil count <1000 cells/µL) (<1.0 x 10^3/µL).
6. Lymphopenia (absolute lymphocyte count <200 cells/µL) (<0.20 x 10^3/µL)
7. Pregnancy or breast feeding
8. Anticipated discharge from the hospital or transfer to another hospital which is not a
study site within 72 hours.
9. Allergy to any study medication.
10. Received monoclonal antibody, convalescent plasma, or intravenous immunoglobulin
[IVIg]) for COVID-19 withing 14 days of screening.
11. Suspected serious, active bacterial, fungal, viral, or other infection (besides
COVID-19) that in the opinion of the investigator could constitute a risk when taking
investigational product.
12. Have a history of VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within
12 weeks prior to screening or have a history of recurrent (>1) VTE (DVT/PE).
13. Subject taking or had taken an anti-androgen of any type including androgen
depravation therapy, 5-alpha reductase inhibitors, etc. within 3 months before dosing.
14. Have participated, within the last 30 days before dosing, in a clinical study
involving an investigational intervention. If the previous investigational
intervention has a long half-life, 5 half-lives or 30 days, whichever is longer,
should have passed.
15. Subjects with active myopathy
16. Is admitted to Intensive Care Units at randomization
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