A Study to Evaluate the Efficacy and Safety of Itolizumab in Subjects Hospitalized With COVID-19

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Itolizumab in Subjects Hospitalized With COVID-19

This is a randomized controlled trial to evaluate the efficacy and safety of itolizumab in subjects hospitalized with COVID-19.

This study will randomize up to 800 subjects in a 1:1 ratio; itolizumab vs. placebo. Subjects will receive either itolizumab or placebo administered intravenously on Day 1 and Day 8 with follow-up to Day 90. Two interim analyses of futility are planned. The first will take place when approximately 20% of the subjects have been evaluated for the primary endpoint, and the second will take place when approximately 50% of the subjects have been evaluated for the primary endpoint.

Inclusion Criteria:

1. Is willing and able to, or has a legally acceptable representative who is willing and able to, provide informed consent to participate and to cooperate with all aspects of the protocol.
2. Is male or female, age ≥18 years
3. Is hospitalized with COVID-19 pneumonia with a diagnosis of SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) or equivalent local test within 14 days of randomization.
4. Has PaO2/FiO2 ratio of ≤200 (or equivalent SpO2/FiO2 ratio ~235 within 24 hours before randomization. This ratio may be adjusted based on altitude.

Exclusion Criteria:

1. Has known severe allergic reactions to mAbs.

2. Has active TB or known history of inadequately treated latent or active TB.

3. Has any known active systemic or pulmonary bacterial, fungal, or viral (other than SARS-CoV-2) infection at the time of randomization.

4. Has known active, uncontrolled hepatitis B or hepatitis C or severe liver function impairment from any etiology, as defined by Child-Pugh Class C.

5. Has human immunodeficiency virus (HIV) with known CD4 counts <0.2 × 10^9/L.

6. Has a history of clinically significant cardiac abnormality within 6 months prior to randomization, such as myocardial infarction or stroke, New York Heart Association class III or IV, or clinically significant abnormalities of electrocardiogram (ECG) or cardiac function.

7. Has been on mechanical ventilation for longer than 48 hours during their first continuous episode since admission, is on their second or greater episode of mechanical ventilation at the time of randomization during the concurrent hospitalization, or has received extracorporeal membrane oxygenation (ECMO).

8. Has a declining clinical status with an expected survival <3 days in the opinion of the Investigator.

9. Has received any systemic immunomodulatory or immunosuppressant agents for any condition within 3 months prior to randomization. (Note: a stable, oral, low dose of corticosteroids [prednisone or equivalent ≤10 mg/day] for a chronic condition or any dose of systemic corticosteroids for current COVID-19 treatment are permitted. Local/topical treatments are also permitted.)

10. Has received any biologic treatment for any acute (eg, COVID-19) or chronic conditions (eg, TNFα inhibitors, anti-IL17A, tocilizumab, anti-cytokines, etc.) within 3 months prior to randomization.

11. Is participating in another clinical study of an investigational product and/or received an investigational product within 30 days or within 5 half-lives (whichever is longer) prior to randomization.

12. Is pregnant or breastfeeding, or has a positive pregnancy serum or urine test during Screening.

13. Does not agree to use contraception in the event of sexual activity for 130 days (+90 days for male subjects) after the last dose of study drug if a female of childbearing potential or a male with a partner of childbearing potential. Note: this criterion does not apply to subjects in same-sex relationships.

14. Has inadequate hematologic function during Screening defined as follows:

    • Absolute neutrophil count (ANC) <1.0 × 109/L.
    • ALC <0.5 × 109/L.

15. Requires renal dialysis, either acute or chronic, at the time of randomization.

16. Has a medical, psychiatric, or other condition or circumstance that, in the opinion of the Investigator, could affect the subject's safety, the subject's participation in the study, or the reliability of the study data.