Ensayos clínicos

Inclusion Criteria:

• Signed Informed Consent Form by any patient capable of giving consent or, when the patient is not capable of giving consent, by his or her legally authorized representative.
• Age ≥ 18 years at time of signing Informed Consent Form.
• Ability to comply with the study protocol.
• Hospitalization with COVID-19 pneumonia confirmed by a positive PCR of any specimen [e.g., respiratory, blood, urine, stool, and other bodily fluids]) and evidence of pneumonia on chest X-ray or CT scan.
• For severe patients, SpO2 ≤93% or PaO2/FiO2 < 300 mmHg:
  • If a patient is on supplemental oxygen with SpO2 > 93%, but desaturation to ≤ 93% on lower supplemental oxygen or ambient air is documented during screening, the inclusion criterion is met.
• For moderate patients (those who do not qualify as severe based oxygen requirements):
  • CRP > 2 x ULN is required.
• For women of childbearing potential:
  • agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below:
    • Women must remain abstinent or use contraceptive methods with a failure rate of <1 % per year during the treatment period and for 90 days after the final dose of TCZ;
    • Women must refrain from donating eggs during this same period;
    • A woman is considered to be of childbearing potential if she is postmenarchal,;
    • has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.
• Examples of contraceptive methods with a failure rate of 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:
  • With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 60 days after the final dose of TCZ to avoid exposing the embryo;
  • Men must refrain from donating sperm during this same period;
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.
  • Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure.
• If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded from study entry:
  • Known severe allergic reactions to TCZ or other monoclonal antibodies;
  • Active TB infection;
  • Suspected active bacterial, fungal, viral, or other infection (besides SARS-CoV-2);
  • Patients who are on a mechanical ventilator > 24 hours or ECMO, in shock, or a combination thereof with other organ failure requiring treatment in an ICU;
  • In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments;
  • Receipt of oral anti-rejection or immunomodulatory drugs (including TCZ) within the past 3 months;
  • Participation in other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if confirmed by the Medical Monitor).
• ALT or AST > 10 x ULN detected within 24 hours at screening or at baseline (according to local laboratory reference ranges).
• ANC < 1000/uL at screening and baseline (according to local laboratory reference ranges).
• Platelet count 50,000/uL at screening and baseline (according to local laboratory reference ranges).
• Pregnancy or breastfeeding, or positive pregnancy test at a predose examination.
• Treatment with an investigational drug within 5 drug-elimination half-lives or 30 days (whichever is longer) of randomization (investigational SARS-CoV-2 [COVID-19]) anti-viral agents may be permitted after consultation with the Medical Monitor).
• Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study.