Phase 3 Inhaled Novaferon Study in Hospitalized Patients With Moderate to Severe COVID-19

NOVATION-1: A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate the Safety and Efficacy of Aerosolized Novaferon + SOC vs. Placebo + SOC in Hospitalized Adult Patients With Moderate to Severe COVID-19

This study is a randomized, double-blind, multicenter, placebo-controlled trial to evaluate the safety and efficacy of a novel therapeutic agent, Novaferon, in hospitalized adult patients diagnosed with COVID-19. The study is comprised of two cohorts:

• Cohort A: This is a blinded safety lead-in comprising two arms. 40 patients will be randomized on a 1:1 basis to receive either Novaferon or matched placebo via a commercial nebulizer, plus Standard of Care (SOC)
• Cohort B: This is the main portion of the study, which comprises two arms. Up to 874 patients will be randomized on a 1:1 basis to receive either Novaferon or matched placebo via a commercial nebulizer, plus SOC

Inclusion Criteria:

Inclusion Criteria:

1. 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 legal/authorized representatives prior to initiation of any study procedures.

2. Men and women, ≥18 years of age at time of enrollment.

3. Laboratory-confirmed diagnosis of SARS-CoV-2 infection as determined by PCR, or other health authority-approved commercial assay or other validated public health assay in any specimen within 72 hours prior to randomization (point-of-care viral infection test allowable if RT-PCR test result not available only at the time of screening).

4. Less than or equal to 9 days from COVID-19 symptom onset to starting treatment.

   • Symptoms are defined as one or more of the following: cough, fever, shortness of breath, chest pain, abdominal pain, nausea/vomiting, diarrhea, body aches, weakness/fatigue, chills/sweating, headache, confusion, sore throat, runny nose/congestion, loss of taste or smell, or any other COVID-19 symptoms as determined by the Investigator.

5. Hospitalized and i) requiring supplemental oxygen by face mask or nasal prongs, or ii) non-invasive ventilation or iii) high-flow oxygen (WHO category 4 or 5)

6. Female patients participating in this study must agree to avoid becoming pregnant and have a negative pregnancy test prior to randomization. Male and female patients of reproductive potential must use a highly effective, protocol-specified method of contraception during the study and up to post 30 days after the last dose of study drug. For a list of protocol-specified contraceptive methods, and the definition of reproductive potential, refer to Appendix 1.

Exclusion Criteria:

Exclusion Criteria:

1. Known hypersensitivity or intolerance to Interferon (IFN) or Novaferon or any excipient(s) of Novaferon, including pre-existing allergy or hypersensitivity to ampicillin.
2. Currently undergoing invasive mechanical ventilation (including venous ECMO).
3. Inability to use a nebulizer with a mouthpiece.
4. ALT/AST > 5 times the Upper Limit of Normal (ULN) or a history of decompensated cirrhosis.
5. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR < 30 mL/min/ 1.73m2).
6. In the opinion of the Investigator, progression to death is imminent and inevitable within the next 48 - 72 hours, irrespective of the provision of treatment.
7. In the opinion of the Investigator, progression to mechanical ventilation is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment.
8. Possibility of the patient being discharged from hospital within 24 hours.
9. Concurrent participation in other anti-COVID-19 therapeutic or interventional trials. Patients may, at the discretion of the Investigator, concurrently participate in other non-interventional COVID-19 studies.
10. Prior or concurrent use of experimental antiviral therapy for COVID-19 (see Appendix 2.
11. Prior or concurrent use of any interferons other than the investigational product (see Appendix 2)
12. Other known active infections or other clinical conditions (e.g., severe chronic obstructive pulmonary disease) that contraindicate aerosolized inhalation.
13. Patients with current or prior psychiatric illness, seizure disorders, retinal autoimmune disorders, pre-existing severe cardiovascular disease, or patients with prior transplants.
14. Females who are breast-feeding, lactating, pregnant or intending to become pregnant.
15. The subject has any medical condition that in the opinion of the investigator would compromise subject's safety or compliance with study procedures.