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
      • Nirmal Hospital Private Limited
  • 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
      • Worthwhile Clinical Trials, 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
• Genders Eligible for Study: All

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 (from randomization)	Sustained clinical improvement is defined as improvement without subsequent worsening. Time to 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 whichever comes first, by Day 29 will be reported.	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 will be reported.	At Days 2, 8, 15, and 29
Duration of Oxygen Use	Duration of oxygen use in terms of days will be reported.	Up to Day 29
Number of Oxygen-free Days	Number of oxygen-free days will be reported.	Up to Day 29
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load	SARS-CoV-2 viral load will be determined by polymerase chain reaction (PCR) in oropharyngeal/nasal swab while hospitalized.	At Days 1, 3, 5, 8, 11, 15, and 29
Duration of Ventilation	Duration of ventilation will be reported in terms of days.	Up to Day 29
Number of Ventilation-free Days	Number of ventilation-free days will be reported.	Up to Day 29
Number of Participants with Any Form of New Ventilation Use	Number of participants with any form of new ventilation use will be reported.	Up to Day 29
Duration of New Ventilation Use	Duration of new ventilation use will be reported in terms of days.	Up to Day 29
Duration of Organ Support	Duration of organ support (e.g., including respiratory, renal, and cardiac support) will be calculated in days.	Up to Day 29
Number of Participants with Response	Response Rate will be 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) will be reported.	At Days 2, 8, 15, and 29
Time to Live Discharge From the Hospital	Time to live discharge from the hospital will be reported.	Up to Day 29
Time From Treatment Start Date to Death	Time from treatment start date to death will be reported.	Up to Day 60
Overall Mortality	Number of deaths will be reported.	At Days 15, 29, and 60
Change in the Ratio of Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2)	Change in the ratio of the oxygen saturation to fraction of inspired oxygen concentration (SpO2/FiO2) will be measured daily from randomization to Day 15, hospital discharge, or death.	From randomization to Day 15, hospital discharge, or death (Up to 90 days)
Number of Participants with Physical Examination Abnormalities	Number of participants with physical examinations (including presenting signs, height, weight) abnormalities will be reported.	Day 1
Number of Participants with Clinical Laboratory Abnormalities	Number of participants with clinical laboratory (Haematology, chemistry, liver function tests, coagulation) abnormalities will be reported.	Up to Day 29
Number of Participants with Vital Signs (blood pressure/heart rate/temperature/respiratory rate) Abnormalities	Number of participants with vital signs (blood pressure/heart rate/temperature/respiratory rate) abnormalities will be reported.	Up to Day 29
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.	From Baseline to Day 90
Duration of Intensive Care Unit (ICU) and Hospitalization	Duration of ICU and hospitalization will be evaluated.	Up to 90 days
National Early Warning Score 2 (NEWS2)	The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).	At Days 15 and 29
Time to NEWS2 of <=2, Maintained for at Least 24 Hours	The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements. The score ranges from 0 (best) to 23 (worst).	At Days 15 and 29
Ranked Trajectory	Ranked trajectory will be calculated over 29 days, with trajectory ranked of the ordinal scale.	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 14, 2021
• Last Update Submitted That Met QC Criteria: October 13, 2021
• Last Verified: October 1, 2021

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; Statistical Analysis Plan (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