Difficulty in COVID-19 subject enrollment

This is a multiregional, randomized, double-blind, placebo-controlled Phase 2 study in patients with confirmed symptomatic COVID-19, designed to evaluate the safety, tolerability, efficacy, and PK of XW001 (IL-29 analog) inhalation solution. The purpose of this study is to evaluate whether treatment with XW001 reduces the likelihood of worsening disease in patients with severe COVID-19. Hospitalized patients on oxygen therapy by mask or nasal prongs (WHO-OSCI score 4) will be enrolled.

Treatment arm patients will receive inhaled XW001 1 mg and placebo arm patients will receive volume-matching placebo 1 mL, once daily, using a commercially available nebulizer for up to 14 days. Treatment should be continued until discharge or progression to score 6 or higher but maximum up to 14 days. Dosing must be started within 48 hours of hospitalization. In addition, both the treatment groups will receive SoC.

The present study is a pilot in the development phase and comprising approximately 120 patients. An independent, external Data Monitoring Committee (DMC) will review all the preliminary clinical data available, including safety, tolerability, efficacy, and PK for the first 20 patients. The decision to recruit the subsequent 100 patients will solely depend on safety and tolerability.

Inclusion Criteria:

1. Male or nonpregnant or nonlactating female, aged 18 to 70 years at the time of consenting

2. Hospitalized due to infection with SARS-CoV-2 confirmed on validated local RT-PCR or other equivalent assays within 48 hours prior to screening and within 96 hours prior to randomization

3. Assessed to be hospitalized cases (rated at WHO-OSCI score 4 [on oxygen therapy by mask or nasal prongs]) within 24 hours prior to randomization

4. Admitted to hospital as clinically indicated for management of severe COVID-19 defined by the following criteria:

   • Positive RT-PCR test for SARS-CoV-2 or an equivalent test

   • Symptom suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness or shortness of breath at rest, or respiratory distress

   • Clinical signs indicative of severe illness with COVID-19, being given oxygenation and meeting one of the following:

     • Respiratory rate ≥30 breaths per minute
     • Heart rate ≥125 beats per minute
     • Oxygen saturation (SpO2) <94% on room air at sea level
     • Arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) <300 mmHg or SpO2/FiO2 <315 mmHg
     • Lung infiltrates >50%

   • No criteria for critical severity

5. Female of childbearing potential must be postmenopausal for 1 year or longer, surgically sterile or having used a medically effective method of contraception for at least 3 months prior to hospitalization

6. Willing and able to provide a signed and dated or electronic informed consent for participation in this study.

Exclusion Criteria:

Patients will be excluded from the study if they satisfy any of the following criteria at the screening visit unless otherwise stated:

1. Having become symptomatic (fever, cough, and other likely symptoms) or positive on virologic test for more than 8 days prior to hospitalization
2. Diagnosed with SARS-CoV-2 confirmed more than 48 hours prior to hospitalization, otherwise reconfirmed positive on repeated RT-PCR (local laboratory) or other equivalent assays within 48 hours prior to randomization
3. Having been hospitalized for more than 48 hours, or showing a worsening medical condition within 48 hours after hospitalization in the opinion of the investigator
4. Known to have received any approved or investigational COVID-19 vaccines within 6 months prior to randomization. Vaccination records can be self-reported by the patient if there is no recorded history
5. Known to have received any approved or investigational therapeutic agents against SARS-CoV-2 including convalescent plasma, monoclonal antibodies, except for remdesivir, dexamethasone, or IL-6 inhibitors as a part of SoC
6. Having received any investigational medicinal products within 90 days of randomization
7. On noninvasive ventilation, eg, continuous positive airway pressure or bilevel positive airway pressure or high-flow oxygen therapy (at WHO-OSCI score 5)
8. Intubated, ventilated (invasively), on any advanced organ/life support (pressors, renal replacement therapy, ECMO), or remaining in the intensive care unit (at WHO-OSCI score 6 and 7)
9. Known to be hypersensitive or allergic to any natural or recombinant protein products
10. Inability to utilize nebulized drugs, or history of bronchospasm with inhaled medications
11. Patients with cardiac disease (New York Heart Association III/IV), liver cirrhosis (>5 x upper limit of normal [ULN]), on chemotherapy, dialysis patients with estimated glomerular filtration rate <30 mL/min/1.73m2, or have other debilitating condition or any other clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, would jeopardize the safety of the patient or non- COVID-19 irreversible underlying condition with projected fatal course within 6 months or with high-risk of mortality
12. Female patients are pregnant or lactating, or male or female patients have a childbearing plan within 30 days prior to randomization until 90 days after the last dosing.