Efficacy and Safety of AXL-Inhibitor bemcentinib for the Treatment of Moderate COVID-19 (AXL-SolidAct)

The primary objective of this study is to evaluate the **efficacy** of bemcentinib combined with standard of care compared to placebo combined with standard of care on the disease state in hospitalized patients with moderate COVID-19. This is clinically relevant as it aims to determine whether bemcentinib can improve outcomes in patients with moderate COVID-19, potentially reducing disease severity and improving recovery rates.

Secondary objectives include:

• Examining the effect of bemcentinib and standard of care versus placebo and standard of care on disease progression within 14 days in hospitalized patients with moderate COVID-19 pulmonary disease.
• Comparing the time to any disease progression by WHO-scale from baseline status between bemcentinib or placebo.
• Comparing the effect of bemcentinib and standard of care versus standard of care and placebo on disease state for up to 28 days after study enrolment.
• Examining the effect of bemcentinib versus placebo on respiratory dysfunction within 7 days in hospitalized COVID-19 patients receiving oxygen at study entry.
• Comparing the efficacy of bemcentinib versus placebo on the occurrence of death.
• Comparing the efficacy of bemcentinib versus placebo on time to sustained recovery.
• Comparing the efficacy of bemcentinib versus placebo on time to first hospital discharge.
• Comparing bemcentinib versus placebo on major serious adverse events.
• Comparing the efficacy of bemcentinib versus placebo on viral clearance.
• Comparing the efficacy of bemcentinib versus placebo on markers of systemic inflammation.
• Comparing the efficacy of bemcentinib versus placebo on patient-reported outcomes (PROM).
• Comparing the general safety and tolerability of bemcentinib versus placebo.

The clinical trial focuses on evaluating the efficacy of bemcentinib combined with standard care versus a placebo in **hospitalised patients** with moderate **COVID-19**. The study population includes both male and female participants over the age of 18, who have a documented laboratory-confirmed SARS-CoV-2 infection, either new or as a reinfection, confirmed by PCR or antigen test within the last 10 days. Participants are required to be admitted to the hospital and present with a moderate disease state, characterized by the absence of oxygen therapy or the need for oxygen by mask or nasal prongs. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. Key inclusion criteria include informed consent and moderate pulmonary COVID-19 disease, defined by lower respiratory symptoms and either the need for oxygen or radiologic evidence of new pulmonary infiltrates consistent with COVID pneumonitis.

The clinical trial is designed to evaluate the **efficacy** and safety of **bemcentinib**, a receptor tyrosine kinase inhibitor, in combination with standard care versus placebo and standard care in hospitalized patients with moderate **COVID-19**. This is a randomized, double-blind, controlled trial, classified as a Phase 4 study. The trial is expected to run from August 29, 2022, to March 29, 2024. Participants will be randomly assigned to receive either bemcentinib or a placebo, both administered orally in capsule form. The maximum daily dose of bemcentinib is 400 mg, with a total maximum dose of 3200 mg over a treatment period of 14 days.

The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 18, documented SARS-CoV-2 infection, and moderate disease state without the need for oxygen therapy. Following randomization, participants will undergo regular follow-up visits to monitor disease progression and safety outcomes. The primary endpoint is the disease state on the 11-point WHO progression scale at Day 8. Secondary endpoints include disease progression, occurrence of death, and various clinical and laboratory measures assessed at Days 15 and 29, and up to 90 days post-randomization.

Participants are expected to be involved in the study for a period of up to 90 days, with the possibility of early termination if serious adverse events occur or if the participant withdraws consent. The end-of-study visit will conclude the trial for each participant, ensuring all necessary data is collected and any remaining health concerns are addressed. The trial aims to provide valuable insights into the potential benefits of bemcentinib in treating moderate COVID-19, contributing to the broader understanding of therapeutic options for this condition.

The clinical trial involves the administration of **Bemcentinib**, a receptor tyrosine kinase inhibitor, as the experimental medication. Bemcentinib is provided in a **capsule** form, with each capsule containing 100 mg of the active substance. The medication is administered **orally**. The dosing regimen allows for a maximum daily dose of 400 mg, with a total maximum dose of 3200 mg over a treatment period of up to 14 days. The chemical origin of the active substance ensures its purity and consistency in formulation. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, the study includes a **placebo** group. The placebo is presented as capsules containing a blend of excipients inside size 0 Swedish Orange Hypromellose capsules. These placebo capsules are designed to match the appearance of the Bemcentinib capsules, ensuring blinding of the study. The placebo is administered in the same manner as the experimental medication, maintaining consistency in the route and frequency of administration. The use of a placebo control allows for the evaluation of the efficacy and safety of Bemcentinib in comparison to standard-of-care therapy in hospitalised patients with moderate COVID-19.

The efficacy of bemcentinib in the treatment of moderate COVID-19 will be assessed using several parameters. The primary endpoint is the disease state on the 11-point WHO progression scale at Day 8. Secondary endpoints include the occurrence of disease progression, defined as a progression from moderate (WHO score 4-5) to severe/critical (WHO score 6-9) or death (WHO score 10) within 14 days, and the occurrence of disease progression by at least a 1-point increase on the 11-point WHO clinical progression scale from baseline within 14 and 28 days of enrollment. Additional secondary endpoints include the disease state on the 11-point WHO scale at Day 15 and Day 29, SaO2/FiO2 ratio at Day 8, occurrence of death within 28 and 60 days, and time from randomization to sustained recovery, defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days within 90 days.

Further assessments involve the time from randomization to first hospital discharge within 90 days, occurrence of serious adverse events leading to study treatment discontinuation or death, viral clearance as assessed by SARS-CoV-2 PCR in naso/oropharyngeal specimens and saliva during hospitalization, and inflammatory biomarkers such as CRP, ferritin, LDH, leukocyte subsets, D-dimer, suPAR, and cytokine panels during hospitalization. Patient-related outcome measures (PROM) will be evaluated using the Oslo COVID-19 QLQ-PW80 questionnaire after 90 days. The occurrence of any treatment-emerging adverse events, including adverse events of special interest, will also be monitored. These efficacy parameters will be measured and collected at specified timepoints, including Day 8, Day 15, Day 29, and up to 90 days post-randomization, using validated scales and laboratory tests.