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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital Hf, Oslo University Hospital Hf

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

24 Aug 2022 → 8 Dec 2023

Decision date (initial)

2022-07-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

BerGenBio ASA · European Union’s Horizon 2020 Research and Innovation Program under grant agreement No 101015736

External identifiers

EU CT number

2022-500363-12-00

WHO UTN

U1111-1278-1806

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is to evaluate the efficacy of bemcentinib and standard of care versus placebo and standard of care on disease state in hospitalised patients with moderate COVID-19.

Secondary objectives 12

1. The core secondary objective is to examine 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.
2. To compare the time to any disease progression by WHO-scale from baseline status between bemcentinib or placebo.
3. To compare 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.
4. To examine the effect of bemcentinib versus placebo on respiratory dysfunction within 7 days in hospitalised COVID19 patients receiving oxygen at study entry.
5. To compare the efficacy of bemcentinib versus placebo on occurrence of death.
6. To compare the efficacy of bemcentinib versus placebo on time to sustained recovery.
7. To compare the efficacy of bemcentinib versus placebo on time to first hospital discharge.
8. To compare bemcentinib versus placebo on major serious adverse events.
9. To compare the efficacy of bemcentinib versus placebo on viral clearance.
10. To compare the efficacy of bemcentinib versus placebo on markers of systemic inflammation.
11. To compare the efficacy of bemcentinib versus placebo on patient reported outcomes (PROM).
12. To compare the general safety and tolerability of bemcentinib vs. placebo

Conditions and MedDRA coding

SARS CoV-2 (COVID-19)

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. GI1. Over 18 years of age
2. GI2. Documented laboratory-confirmed SARS-CoV-2 infection (new infection or reinfection) as determined by PCR or antigen test in any specimen not more than 10 days old.
3. GI3. Admitted to hospital.
4. GI4. Informed consent by the participant.
5. GI5. Moderate disease state defined as hospitalised patients without oxygen therapy or oxygen by mask or nasal prongs needed.
6. SI-01. Moderate pulmonary COVID19 disease defined as mainly lower respiratory symptoms and either: i) need of oxygen by mask or nasal prongs, or ii) current radiologic evidence of new pulmonary infiltrates consistent with COVID pneumonitis.

Exclusion criteria 20

1. GE1. Anticipated transfer to another non-trial hospital within 72 hours.
2. SE-09. Severe chronic kidney disease. Subjects with estimated glomerular filtration rate (eGFR) <30 millilitre/minute/1.73 meters squared are excluded.
3. SE-10. Individuals with clinically significant hypokalaemia (<3.0 mmol/l) are excluded. Note: Individuals who do not meet this criterion may be rescreened once, after correction of electrolyte abnormality.
4. SE-11: Patients on current or planned pharmaceutical treatment for tuberculosis.
5. SE-12. Are pregnant or breastfeeding, or intend to become pregnant or breastfeed during the study. Note: Women of childbearing potential (WOCBP) can only be included based on a negative pregnancy test and WOCBP must comply with requirements regarding highly effective contraception. Refer to section 10.1 for contraception requirements for women and men.
6. SE-13. Participation in other therapeutic clinical trial for COVID-19.
7. SE-14. Allergy to any component of the study treatment. Note: Bemcentinib or placebo capsules contain Capsule core: lactose monohydrate, microcrystalline cellulose, crosspovidone, polyvinylpyrrolidone, colloidal silicon dioxide and magnesium stearate. Capsule: hypromellose, red iron oxide, titanium dioxide Note: Participants who are lactose intolerant should not be included.
8. SE-15. Severe COVID-19, defined as SaO2 < 90% on room air, and/or need of high flow oxygen, non-invasive ventilation, mechanical ventilation or ECMO.
9. SE-16. Had COVID-related symptoms > 10 days or hospitalised with COVID-19 > 4 days.
10. SE-01. Unable to swallow capsules.
11. SE-02 Hospitalised for reasons other than pulmonary COVID19 disease, unless developing nosocomial pulmonary COVID-19 during hospitalisation
12. SE-03. History any of the following cardiac conditions: Myocardial infarction within 3 months prior to the first dose; Unstable angina; History of clinically significant dysrhythmias (long QT features on ECG, sustained bradycardia [≤55 bpm]), left bundle branch block, or ventricular arrhythmia) or history of familial long QT. Note: Patients with an implantable cardioverter defibrillator device in place, will be allowed to enrol. Atrial fibrillation will not be a reason for exclusion.
13. SE-04. Screening 12-lead ECG with a measurable QT interval according to Fridericia correction (QTcF) >470 msec (triplicate at baseline).
14. SE-05. Treatment with a concomitant medication with increased risk of Torsade-de-Pointes arrhythmia or significant electrocardiographic QT prolonging effect that cannot be safely discontinued. Note: The list includes but is not limited to (in alphabetical order) Amiodarone, Astemizole, Azithromycin, Chloroquine, Citalopram, Clarithromycin, Cocaine, Disopyramide, Droperidol, Erythromycin, Escitalopram, Fluconazole, Haloperidol, Ketoconazole, Methadone, Moxifloxacin, Ondansetron, Petamidine, Pimozide, Procainamide, Quinidine, Sotalol, Terfenadine, Thioridazine, Voriconazole. Concomitant treatment with CYP 3A4 substrates that have a narrow therapeutic window should also be discontinued (with the exception of fluticasone detailed below). The following should be discontinued (in alphabetical order) Alfentanyl, Cisapride, Cyclosporine, Ergotamine/ Dihydroergotamine, Fentanyl , Sirolimus, Tacrolimus. Fluticasone may continue without interruption when administered either nasally or inhaled. Note: If a medication can be safely discontinued, the 2-day bemcentinib loading regime may be started as long as the QTcF on prior therapy is not prolonged above that required for eligibility (470 ms).
15. SE-06. Therapeutic anticoagulation with vitamin K antagonists.
16. SE-07. Previous bowel resection/ bowel dysfunction that would interfere with drug absorption.
17. SE-08. Alanine aminotransferase/aspartate aminotransferase ≥ 5 × the upper limit of normal.
18. SE-17. Experimental off-label usage of medicinal products as treatments for COVID-19 at the time of enrolment unless these are defined as SOC.
19. SE-18. Neutrophil count <500 cells/uL
20. SE-19. Known uncontrolled chronic viral infection (including HIV, HBV, HCV). Note: Screening for viral infections is not mandatory.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease state on the 11-point WHO progression scale at Day 8.

Secondary endpoints 12

1. Occurrence of disease progression, defined as a progression of disease state from moderate (WHO score 4-5) to severe/critical (WHO score 6-9) or death (WHO score 10) within 14 days.
2. Occurrence of disease progression by at least 1 point increase on the 11-point WHO clinical progression scale from baseline within 14 days and 28 days of enrolment.
3. Disease state on the 11-point WHO scale at Day 15 and Day 29.
4. SaO2/FiO2 ratio at day 8.
5. Occurrence of death within 28 and 60 days.
6. 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.
7. Time from randomization to first hospital discharge within 90 days.
8. Occurrence of serious adverse events leading to study treatment discontinuation or death.
9. Viral clearance as assessed by SARS-CoV2 PCR in naso/oropharyngeal specimens and saliva during hospitalization.
10. Inflammatory biomarkers (CRP, ferritin, LDH, leukocyte subsets, D-dimer, suPAR, cytokine panels) during hospitalisation.
11. Patient related outcome measures (PROM) by the Oslo COVID-19 QLQ-PW80 questionnaire after 90 days.
12. Occurrence of any treatment emerging adverse events, including adverse events of special interest.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital Hf

Sponsor organisation

Oslo University Hospital Hf

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital Hf

Contact name

Inge C. Olsen

Public contact point

Organisation

Oslo University Hospital Hf

Contact name

Thale Patrick-Brown

Third parties 1

Oslo University Hospital Hf

Sponsor organisation

Oslo University Hospital Hf

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital Hf

Contact name

Inge C. Olsen

Public contact point

Organisation

Oslo University Hospital Hf

Contact name

Thale Patrick-Brown

Third parties 1

Locations

10 EU/EEA countries · 50 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 9 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications