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

A Multicentre, Phase 2, Randomised Study to Assess the Efficacy and Safety of Bemcentinib for the Treatment of COVID-19 in Hospitalised Patients

The primary objective of the study is to evaluate the efficacy of bemcentinib as an add-on therapies to standard of care (SoC) in participants hospitalized with coronavirus disease 2019 (COVID-19).

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Bemcentinib; Other: SoC

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • New Delhi, India, 110002
    • Maulana Azad Medical College
  • Gujarat
    • Surat, Gujarat, India, 395002
      • Unity Trauma Center and ICU, Unity Hospital
  • Karnataka
    • Mangalore, Karnataka, India, 575001
      • Kasturba Medical College
    • Mysuru, Karnataka, India, 570 004
      • JSS Hospital
  • Maharashtra
    • Nashik, Maharashtra, India, 422005
      • Chopda Medicare & Research Centre Pvt. Ltd (CMARC) - Magnum Heart Institute
  • Maharastra
    • Pune, Maharastra, India, 411004
      • Sahyadri Specialty Hospital
  • Telangana
    • Secunderabad, Telangana, India, 500003
      • Krishna Institute of Medical Sciences (KIMS Hospitals)
• South Africa
  • Worcester, South Africa
    • Clinical Projects Research
  • Benoni
    • Mowbray, Benoni, South Africa
      • Lakeview Hospital
  • Cape Town
    • Bellville, Cape Town, South Africa
      • Tiervlei Trial Centre
    • Somerset West, Cape Town, South Africa
      • Vergelegen Mediclinic
  • Pretoria
    • Groenkloof, Pretoria, South Africa
      • Into Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults (greater than or equal to [>=] 18 years) with SARS-CoV-2 infection.
• Participants with symptoms and/or signs consistent with COVID-19, requiring treatment.
• A score of Grade 3 to 5 on the 9-point ordinal scale. In India; only Participants with a score of Grade 4 or 5 will be enrolled.
• a) Male Participants:

• A male Participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.

  b) Female Participants:

• A female Participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:

  1. Not a woman of childbearing potential. OR
  2. A woman of childbearing potential who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• Women who are lactating who agree not to breastfeed their child during the study and for at least 120 days after termination of study therapy (they may continue to express milk away from the child during this period, but this milk must be discarded).
• Ability to provide informed consent signed by the study Participant or legally authorized representative.

Exclusion Criteria:

• Participants who have previously had a score of 6 or 7 on the 9-point ordinal scale.
• Inability to swallow capsules (administration via nasogastric tube is permitted in Participants who become unable to swallow after starting the study drug).

• History of the following cardiac conditions:

  1. Myocardial infarction within 3 months prior to the first dose
  2. Unstable angina
  3. History of clinically significant dysrhythmias (long QT features on electrocardiogram [ECG], sustained bradycardia [less than or equal to {<=} 55 beats per minute {bpm}]), left bundle branch block, or ventricular arrhythmia) or history of familial long QT. Participants with an implantable cardioverter defibrillator device in place, will be allowed to enroll. Atrial fibrillation will not be a reason for exclusion.
• Screening 12-lead ECG with a measurable QT interval according to Fridericia correction (QTcF) greater than (>) 470 msec.
• Clinically significant hypokalaemia.
• Therapeutic anticoagulation with vitamin K antagonists.
• Previous bowel resection that would interfere with drug absorption.
• Any participant whose interests are not best served by study participation, as determined by a senior attending clinician.
• Alanine aminotransferase/aspartate aminotransferase >5 × the upper limit of normal.
• Current treatment for human immunodeficiency virus (HIV) or tuberculosis (TB).
• Positive serologic assay at screening for hepatitis B virus (Hep B surface antigen) or hepatitis C virus (hepatitis C PCR or hepatitis C core antigen) at local laboratory.
• Stage 4 severe chronic kidney disease.
• Anticipated transfer to another hospital that is not a study center within 72 hours.
• Allergy to any study treatment.
• Experimental off-label usage of medicinal products as treatments for COVID-19 at the time of enrolment.
• Participants participating in another clinical study of an investigational medicinal product.
• Current or planned treatment for TB.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard of Care + Bemcentinib; Bemcentinib will be administered for up to 15 days, or until discharge from hospital, whichever comes sooner. SoC will be administered based on local guidelines.	Drug: Bemcentinib; Bemcentinib capsules will be administered orally.; Other: SoC; The SoC will be administered based on local guidelines.
Active Comparator: Standard of Care; The SoC will be administered based on local guidelines in place at the time of treatment during the study.	Other: SoC; The SoC will be administered based on local guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Sustained Clinical Improvement of at Least 2 Points	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.	From randomization up to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Not Deteriorating According to the Ordinal Scale by 1, 2, or 3 Points	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.	At Days 2, 8, 15, and 29
Duration of Oxygen Use (in Percentage)	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).	Up to Day 29
Duration of Oxygen-free Days (in Percentage)	In this outcome measure percentage of hospitalization days which were oxygen-free days was reported.	Up to Day 29
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load	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).	Day 1 (Baseline), 3, 5, 8, 11, 15, and 29
Duration of Ventilation Use (in Percentage) by Hospital Survival Status	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.	Up to Day 29
Duration of Ventilation-free Days (in Percentage)- by Hospital Survival Status	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.	Up to Day 29
Number of Participants With Any Form of New Ventilation Use	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.	Up to Day 29
Duration of New Ventilation Use (in Percentage) by Hospital Survival Status	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.	Up to Day 29
Duration of Organ Support (in Percentage)	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.	Up to Day 29
Number of Participants With Response	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.	At Days 2, 8, 15, and 29
Time to Live Discharge From the Hospital	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.	Up to Day 29
Time to Death	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.	Up to Day 60
Overall Mortality	Number of participants who died were reported.	At Days 15, 29, and 60
Change From Baseline in the Ratio of Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2)	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).	Baseline, Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Number of Participants With Adverse Events (AEs)	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.	Up to Day 90
Duration of Intensive Care Unit (ICU)- (in Percentage)	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.	Up to 90 days
Duration of Hospitalization	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.	Up to 90 days
National Early Warning Score 2 (NEWS2)	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).	At Days 15 and 29
Time to NEWS2 of <=2, Maintained for at Least 24 Hours	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.	Up to Day 29
Ranked Trajectory Over 29 Days	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.	29 days

Collaborators and Investigators

• Sponsor: BerGenBio ASA
• Investigators: Study Chair: Hani Gabra, BerGenBio ASA

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2020
• Primary Completion (Actual): May 25, 2021
• Study Completion (Actual): May 25, 2021

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: BGBC020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the article, after deidentification [text, tables, figures and appendices].
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication
• IPD Sharing Access Criteria: Proposal should be directed to HYPERLINK "mailto:clinical@bergenbio.com" clinical@bergenbio.com. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No