Trial Outcomes & Findings for A Study of Bemcentinib for the Treatment of COVID-19 in Hospitalised Patients (NCT NCT04890509)

A Study of Bemcentinib for the Treatment of COVID-19 in Hospitalised Patients

Sustained clinical improvement is defined as improvement without subsequent worsening. Time to sustained clinical improvement (in days) from randomization is defined as the number of days to a sustained improvement of at least 2 points on a 9-point category ordinal scale, or live discharge from the hospital, or fit for discharge, whichever occurs first by Day 29. 9-point category ordinal scale: 0-Uninfected, no clinical or virological evidence of infection; 1-Ambulatory, no limitation of activities; 2-Ambulatory, limitation of activities; 3-Hospitalised - mild disease, no oxygen therapy; 4-Hospitalized - mild disease, oxygen by mask or nasal prongs; 5-Hospitalized - severe disease, non-invasive ventilation or high-flow oxygen; 6-Hospitalized - severe disease, intubation and mechanical ventilation; 7-Hospitalized - severe disease, ventilation and additional organ support - vasopressors, renal replacement therapy, extracorporeal membrane oxygenation; 8-Death.

Percentage of participants not deteriorating according to the 9-point category Ordinal Scale (0= uninfected and 8= Death), by 1, 2, or 3 points was reported. Deterioration by 1, 2 or 3 points at days 2, 8, 15 and 29 is defined as an increase in ordinal scale score of at least 1, 2 or 3 points respectively compared to baseline. Participants who had no ordinal score measured at a Day and who were discharged from hospital prior to that Day had their ordinal score used from the most recent value recorded prior to the Day. Participants who died prior to a Day have a score of 8 used for all Days after death. All other participants with no ordinal score measured at a day are considered to have deterioration at that Day.

In this outcome measure percentage of hospitalization days during which oxygen was used is reported. The duration of each occurrence of oxygen use was derived based on the start date and time, and end date and time of the use of any type of supplemental oxygen (including mechanical ventilation) as captured in the electronic case report form (eCRF). For each participant, the duration in days of oxygen use was derived as the sum of the duration (in minutes) of each occurrence of oxygen use, divided by 1440 (24\*60).

In this outcome measure percentage of hospitalization days which were oxygen-free days was reported.

SARS-CoV-2 viral load was determined by polymerase chain reaction (PCR) in oropharyngeal and nasal swab while hospitalized. Baseline is defined as the non-missing measurement taken prior to or on randomization day (including unscheduled measurements, if any).

In this outcome measure percentage of hospitalization days during which ventilation was used. Duration of ventilation use by hospital survival status was reported in terms of days. Alive is defined as a participant who did not die whilst in hospital and died is defined as a participant who died whilst in hospital. The duration of ventilation was derived based on the start date and time, and end date and time of either invasive mechanical ventilation or non-invasive mechanical ventilation as the type of supplemental oxygen captured in the eCRF.

In this outcome measure percentage of hospitalization days which were ventilation-free by hospital survival status was reported. Alive is defined as a participant who did not die whilst in hospital and died is defined as a participant who died whilst in hospital.

Number of participants with any form of new ventilation use was reported. New ventilation was defined as either Invasive Mechanical Ventilation or Non-Invasive Mechanical Ventilation as the type of supplemental oxygen captured in the eCRF that was not occurring at the time of randomization.

In this outcome measure percentage of hospitalization days during which new ventilation was used. The duration of new ventilation was derived based on the start date and time, and end date and time of either invasive mechanical ventilation or non-invasive mechanical ventilation as the type of supplemental oxygen captured in the eCRF that was not occurring at the time of randomization. Alive is defined as a participant who did not die whilst in hospital and died is defined as a participant who died whilst in hospital.

In this outcome measure percentage of hospitalization days during which organ support (e.g., including respiratory, renal, and cardiac support) was provided is reported in days. Organ support was approximated from the following adverse events of special interests (AESIs) when treatment was received: Cardiovascular organ failure; Renal organ failure requiring renal replacement therapy; Liver organ failure. For each participant the duration of AESIs was summed, noting that if there are any overlapping dates of AESIs, days were only counted once for a participant.

Response rate was assessed on a 9-point category ordinal scale. Number of participants with response (defined as sustained clinical improvement of at least 2 points (from randomization) on a 9-point category ordinal scale, live discharge from the hospital, or considered fit for discharge (a score of 0, 1, or 2 on the ordinal scale), whichever comes first) was reported. Participants who were not discharged or who had no ordinal scale assessment on a particular study day (including participants who have died prior to that study day) were considered non-responders.

Time to live discharge from the hospital (in days) was calculated from randomization. It was derived as: (date of discharge - date of randomization) +1. Participants who were alive and still in hospital at the time of analysis had their time to discharge censored at the data cut-off date for the analysis. Participants who died at the time of analysis, without having been discharged from hospital, had their time to live discharge censored at Day 29.

Time to death (in days) was calculated from randomization. Participants who were not known to have died at the time of analysis had their time to death censored at the last date the participant was known to be alive.

Number of participants who died were reported.

Change from baseline in the ratio of the oxygen saturation to fraction of inspired oxygen concentration (SpO2/FiO2) was measured daily from randomization to Day 15. Baseline is defined as the last non-missing measurement taken prior to randomization (including unscheduled measurements, if any).

An AE is any untoward medical occurrence in participants, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

In this outcome measure percentage of hospitalization days for which participant was in ICU is reported. Duration of ICU was derived based on start/stop date of admission and start/stop date of ICU stay in the eCRF. Duration of ICU is the sum of duration (days) of each episode of ICU/HDU stay. If a participant died and the stop date of admission is missing, the date of death was used instead.

Duration of hospitalization (days) was derived based on start/stop date of admission and start/stop date of HDU stay in the eCRF. Duration of hospitalization is derived as stop date of admission minus start date of admission +1. If a participant died and the stop date of admission is missing, the date of death was used instead.

NEWS2 is based on 6 physiological measurements (respiration rate, oxygen saturation \[SpO2\], systolic blood pressure, pulse rate, level of consciousness or new confusion, and temperature). Each of these physiological parameters is rated using a 4-point Likert scale (0= no risk to 3 = high risk). The NEWS2 score is obtained by summing the 6 physiological parameter individual scores, with higher score indicating higher risk of deterioration and need for escalation in clinical care, including transfer of the participant to a higher level of care hospital unit. The NEWS2 score is set to missing if at least 1 physiological parameter individual score is missing, and the overall score is uplifted by 2 points for patients requiring supplemental oxygen to maintain their recommended SpO2. The range of NEWS2 score, taking into account this potential 2 point uplifting, is 0 (best) to 20 (worst).

The NEWS2 is based on is based on 6 physiological measurements. The range of NEWS2 score, is from 0 (best) to 20 (worst). Time to NEWS2 \<=2 maintained for at least 24 hours (in days) was calculated from randomization as: The date of the first post-Baseline assessment where NEWS2 is \<= 2 and sustained for at least 24 hours ) - date of randomization +1.

Ranked trajectory is not a scale outcome measure and does not have a validated scale range. It is an evaluation of dynamic changes over time in the ordinal scale (9-point; 0= uninfected to 8= death; higher scores = more severity) of severity based on individual rank. It was calculated over 29 days. Each participant ranks were assigned based on the following order of the ordinal scale, \[1\] The worst (highest) score, Ascending; \[2\] The last recorded score, Ascending; \[3\] The number of days at worst score, Ascending; \[4\] The best(lowest) score that occurred after the worst score, Ascending; \[5\] The number of days the participant was at \[4\], Descending. Orderings performed at steps \[2\], \[3\], \[4\] and \[5\] were used to resolve any tied ranks resulting from previous step. Each participant had one overall rank for their trajectory. There was no rank range associated, however lower rank = better trajectory.