sponsor strategy change

This is a randomized, multicenter, placebo-controlled, double-blind clinical study in patients hospitalized due to severe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

Eligible 300 hospitalized patients with confirmed severe SARS-CoV-2 infection will be randomly assigned (1:1) to receive 14 days treatment of 400 mg carrimycin and standard of care (SOC) or placebo and SOC.

Inclusion Criteria:

• Patient with SARS-CoV-2 infection as determined by real time polymerase chain reaction (RT- PCR) or other commercial or public health assay in any specimen taken ≤ 4 days prior to randomization. Onset of symptoms of COVID-19 must be 14 or fewer days prior to randomization. Patient with a second SARS-CoV-2 episode after resolution of the initial infection may be enrolled if the initial infection had clearly resolved, re-infection is reconfirmed by RT-PCR and all other eligibility criteria are met
• Hospitalized patient who requires oxygen supplementation via either low-flow oxygen device (such as nasal cannula or face mask), high flow oxygen therapy (including high-flow nasal cannula), or non invasive ventilation to maintain peripheral oxygen saturation of at least 94%. The patient must have had such an oxygen requirement for 2 days or fewer at the time of Screening, and the oxygen requirement must be non-improving (worsening or stable) in the Investigator's judgement at the time of Screening and randomization
• Female patient of childbearing potential and male patient with female partner of childbearing potential must agree to use at least one primary form of contraception for the duration of the study
• Ability to provide informed consent personally, or by a legally acceptable representative if the patient is unable to do so
• Patient is willing and able to comply with all required study visits and follow up required by the protocol
• Patient must agree not to enroll in another study of an investigational agent prior to completion of Day 60 of study

Exclusion Criteria:

• Non-hospitalized patients, including those requiring home oxygen support

• Patient has a creatinine clearance < 50 mL/min/1.73m^2 using the modification of diet in renal disease formula

• Patient cannot take the study drug by mouth and needs to be administered by nasogastric tube at Screening.

• Patient has a known allergy to any study medication or macrolides

• Patient with known medical history of hepatitis B or, if tested, presence of hepatitis B surface antigen at Screening

• Patient has a known medical history of hepatitis C or positive hepatitis C antibody test result at Screening (if obtained)

• Patient has a positive hepatitis C RNA test result at Screening

• Patient has a known medical history of human immunodeficiency virus (HIV) infection or was seropositive for human immunodeficiency virus (if tested)

• Patient has been treated with anti-tumor therapy with immunosuppressive effects, which includes chemotherapy, biologics and hormonal therapy in the past 30 days prior to Screening

• Patient has used a macrolide in the week prior to Screening

• Patient has used antiviral drugs which are not part of SOC < 24 hours prior to Day 1

• Patient receiving hemoperfusion or with anticipated use of hemoperfusion (including when hemoperfusion is a part of SOC)

• Patient has used the following types of medications < 2 days prior to Day 1 and/or plans to initiate such medications during the treatment period without an appropriate alternative therapy:

  1. Narrow therapeutic index substrates of cytochrome P450 (CYP) enzymes
  2. Narrow therapeutic index substrates of major transporters: organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1, OATP1B3), organic anion transporter 1 and 3 (OAT1, OAT3), organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 and 2-K (MATE1, MATE2K)
  3. Strong inhibitors and/or inducers of enzymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5
  4. Strong inhibitors of transporters OATP1B1 and OATP1B3
  5. Note: strong inhibitors of OAT1/OAT3, OCT2 and MATE1/MATE2K should be avoided when possible, but when unavoidable investigators may assess the risks and benefits and to continue treatment with such medications under close observation for adverse events

• Patient has consumed foods and/or used herbal medicines with strong CYP3A4 or CYP3A5 effects

• Patient who, in the judgment of the Investigator, will be unlikely or unable to comply with the requirements of this protocol through Day 60

• Female patient who is pregnant or breastfeeding

• Critical patient with a life expectancy < 48 hours

• Patient who has received an organ transplant in the past 6 months prior to Screening or is on the waiting list for organ transplantation

• Patient with evidence of multiorgan failure (defined as two or more organs failing) or septic shock

• Patient requiring mechanical ventilation or extracorporeal membrane oxygenation at Screening

• Patient has a mean corrected QT interval using Fridericia's formula (QTcF) of > 450 msec (for male patients) and > 470 msec (for female patients) at Screening

• Patient who has a history of alcohol abuse within 3 months prior to the study as judged by the Investigator