Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial

Inclusion Criteria:

• Confirmation of SARS-CoV2 infection by nucleic acid test (NAT) or equivalent non-NATtest [list of approved tests in the PIM] within 14 days of randomization.

• Requiring hospitalization for the management of COVID-19

• Has evidence of COVID-19 pneumonia (PNA) defined as either receiving supplementaryoxygen ≤2L of low flow oxygen with evidence of airspace disease on chest imaging (Xray, computer tomography or ultrasound) OR receiving supplementary oxygen >2L and <10 L of low flow oxygen.

• Currently receiving or planned to receive (ordered) one IM drug (for example, acorticosteroid or baricitinib) as part of treatment of COVID-19 prior torandomization.

• Has started supplemental oxygen for the treatment of COVID-19 within the past 5calendar days. Patients on home oxygen are eligible if current oxygen flow rate isincreased from baseline and other above criteria are met.

• Investigator agrees that the pneumonia is due to COVID-19.

Exclusion Criteria:

• Oxygen requirement of ≥10L or more of low flow oxygen (or equivalent if usingVenturi mask, etc), or requiring either HFNO, NIV, IMV, or ECMO.

• Participant has received more than one baseline IM for treatment of the currentCOVID-19 infection at time of trial enrollment. (Examples: corticosteroid,baricitinib, tocilizumab, anakinra, abatacept, or infliximab.)

• Participant anticipated to not meet all inclusion criteria within 24 hours ofrandomization in the opinion of the investigator.

• Allergy to investigational agent.

• Neutropenia (absolute neutrophil count <1000 cells/μL) (<1.0 x 10 3 /μL or <1.0 G/L)on most recent lab within 2 calendar days of randomization.

• Lymphopenia (absolute lymphocyte count <200 cells/μL) (<0.20 x 10 3 /μL or <0.20G/L) on most recent lab within 2 calendar days of randomization.

• Known or suspected active or recent serious infection (bacterial, fungal, viral, orparasitic infection, excepting SARS-CoV-2) that in the opinion of the investigatorcould constitute a risk when taking investigational agent. Note: Broad spectrumempiric antibiotic usage does not exclude participation.

• Known or suspected history of untreated tuberculosis (TB). TB diagnosis may besuspected based on medical history and concomitant therapies that would suggest TBinfection. Participants are also excluded if they have known, latent TB treated forless than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).

• Have received any live vaccine (or live attenuated) within 3 months before screeningor intend to receive a live vaccine (or live attenuated) during the trial. Use ofprior non-live (inactivated) vaccinations is allowed for all participants, includingany vaccine for COVID-19.

• Pre-existing immunomodulation or immunosuppression that meets any of the following:Participant has received abatacept for an indication other than COVID- 19 within 5half-lives (65 days) of enrollment (Abatacept elimination half-life is 13.1 days.)Participant is receiving immune modulatory therapy for autoimmune, transplantmanagement or another indication AND has one or more of the following: evidence ofactive infection (other than COVID-19) or has required reduction in their immunemodulatory therapy in the preceding 6 months due to infectious complication (routinereduction as SOC is not an exclusion) or has required intensification inimmunotherapy within the preceding 6 months due to organ rejection/worseningunderlying disease status (e.g., intensification with an additional agent on top ofusual immunosuppressive regimen)

• Participant has recently received or is anticipated to require immune modulatoryagents for their underlying disease including chemotherapeutic treatments likely toinduce neutropenia (&lt;1.0 x 10 9 cells/µL) or lymphopenia (&lt;1.0 x 10 9cells/µL)

• Participant has untreated advanced HIV (known CD4 &lt;200 in the past 6 months) ANDis not established on antiretroviral therapy

• Pregnancy

• Breastfeeding

• Co-enrollment in other trials not predetermined to be compatible with this trial.

• In the investigator's judgment, the patient has any advanced organ dysfunction thatwould not make participation appropriate.

• The treating clinician expects inability to participate in trial procedures orparticipation would not be in the best interests of the patient.