Study of Efficacy and Safety of DV890 in Patients With COVID-19 Pneumonia

Phase 2, Randomized, Controlled, Open Label Multi-center Study to Assess Efficacy and Safety of DFV890 for the Treatment of SARS-CoV-2 Infected Patients With COVID-19 Pneumonia and Impaired Respiratory Function

This clinical study was designed to assess the efficacy and safety of DFV890 for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infected patients with coronavirus disease 2019 (COVID-19) pneumonia and impaired respiratory function.

This was a Phase II, randomized, controlled, open label multi-center study to assess the efficacy and safety of DFV890 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function.

The study consisted of four distinct study periods:

Screening / Baseline visit (Day -1 to 1): lasted up to a maximum of 24 hours and comprised a screening / baseline assessment. This visit was used to confirm that the study inclusion and exclusion criteria were met and served as baseline assessment prior to randomization.

Treatment period (Day 1-15): Participants were randomized as soon as possible, but within a maximum of 24 hours after screening in a 1:1 ratio receiving either DFV890 in addition to standard of care (SoC) or SoC alone. Participants in the investigational treatment arm received DFV890 administered for a total of 14 days in addition to SoC. Participants in the control arm received SoC alone. Study assessments were conducted every 2 days for hospitalized participants.

The End of Treatment (EOT) visit took place on Day 15. If participants were discharged from the hospital prior to Day 15, assessments on the day of discharge were performed according to the schedule listed under Day 15; participants continued to take the investigational treatment at home to complete the 14-day treatment period and the participants returned to the site for the Day 15/EOT assessment. If a hospital visit was not possible at Day 15, then home nursing services were used to support the last visit.

Follow-up (Day 16-29): After completion of the treatment period, participants were observed until Day 29 or discharged from hospital, whichever was sooner. Study assessments were conducted every 2 days for hospitalized participants. If participants were discharged from hospital prior to Day 29, a study visit conducted by telephone was performed on Day 29.

30-day safety follow-up assessment (Day 45): A follow-up visit for safety was conducted by telephone.

Inclusion Criteria:

• Male and female patients aged 18-80 years inclusive at screening.
• Clinically diagnosed with the SARS-CoV-2 virus by polymerase chain reaction (PCR) or by other approved diagnostic methodology within 7 days prior to randomization.
• Hospitalized with COVID-19-induced pneumonia evidenced by chest X-ray, computed tomography scan (CT scan) or magnetic resonance scan (MR scan), taken within 5 days prior to randomization (within 24 hours in patients in the Netherlands).
• Impaired respiratory function, defined as peripheral oxygen saturation (SpO2) ≤93% on room air or partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) <300 millimeter of mercury (mmHg) at screening. For cities located at altitudes greater than 2500 m above sea level, these will be substituted with SpO2 <90% and PaO2/FiO2 <250 mmHg.
• APACHE II score of ≥10 at screening.
• C-reactive protein (CRP) ≥20 mg/L and/or ferritin level ≥600 μg/L at screening.
• Body mass index of ≥18 to <40kg/m2 at screening.

Exclusion Criteria:

• Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal, viral, or other infection (besides SARS-CoV-2).
• In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment.
• Intubated prior to randomization.
• Previous treatment with anti-rejection and immunomodulatory drugs within the past 2 weeks, or within the past 30 days or 5 half-lives (whichever is the longer) for immunomodulatory therapeutic antibodies or prohibited drugs, with the exception of hydroxychloroquine, chloroquine or corticosteroids:

For COVID-19 infection, ongoing corticosteroid treatment is permitted at doses as per local SoC.For non-COVID-19 disorders, ongoing corticosteroid treatment is permitted at doses up to and including prednisolone 10 mg daily or equivalent.

In patients in the Netherlands only, the use of hydroxychloroquine and/or chloroquine in the past 2 weeks are exclusionary.

• Serum alanine transaminase (ALT) or aspartate transaminase (AST) >5 times upper limit of normal detected within 24 hours at screening or at baseline (according to local laboratory reference ranges) or other evidence if severe hepatic impairment (Child-Pugh Class C).
• Absolute peripheral blood neutrophil count of ≤1000/mm3.
• Estimated GFR (eGFR) ≤30 mL/min/1.73m2 (based on CKD-EPI formula).
• Patients currently being treated with drugs known to be strong or moderate inducers of isoenzyme CYP2C9 and/or strong inhibitors of CYP2C9 and/or strong inducers of cytochrome P450, family 3, subfamily A (CYP3A) and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment.
• Patients with innate or acquired immunodeficiencies.
• Patients who have undergone solid organ or stem cell transplantation.