PROphylaxis for paTiEnts at Risk of COVID-19 infecTion -V (PROTECT-V)
Covid19
About this trial
This is an interventional prevention trial for Covid19 focused on measuring dialysis, solid organ transplant, vasculitis, glomerulonephritis, systemic lupus erythematosus, haematopoietic stem cell transplant, oncology or haematology patient who is or has received chemotherapy or who is immunocompromised as a result of their disease or treatment, diagnosis of an autoimmune/inflammatory disease currently receiving immunosuppression, primary immunodeficiency
Eligibility Criteria
Core protocol
Inclusion Criteria:
- Be aged 18 years or older
- Have given written informed consent
Be a member of one of the following vulnerable patients populations ○ Dialysis - including in centre haemodialysis, home haemodialysis and peritoneal dialysis
- Kidney transplant receiving at least one of the immunosuppressive medications listed below
- Vasculitis (according to Chapel Hill Consensus Conference 2012 definitions) or systemic lupus erythematosus (SLE) receiving at least one of the immunosuppressive medications listed below
- Glomerulonephritis (includes prior histological confirmation of any of the following conditions - minimal change nephropathy, focal segmental glomerulosclerosis (FSGS), IgA nephropathy, primary membranous nephropathy, membranoproliferative glomerulonephritis or lupus nephritis) receiving at least one of the immunosuppressive medications listed below Ciclosporin Tacrolimus Azathioprine Mycophenolate Mofetil or Mycophenolic Acid Belatacept Methotrexate Tocilizumab Abatacept Leflunomide Sirolimus Prednisolone (current dose) > 20mg daily for 8 weeks Anti-TNF (infliximab, adalimumab, etanercept) Belimumab Cyclophosphamide (within the last 6 months) Rituximab (in the last 12 months) or Rituximab in the last 5 years and IgG level <5g/l Alemtuzumab (in the last 12 months)
Exclusion Criteria:
- Inability to provide informed consent or to comply with trial procedures
- COVID-19 at time of enrolment - either positive SARS CoV-2 swab (PCR) or symptoms highly suggestive of COVID-19 infection
- Known chronic liver disease or hepatic dysfunction as evidenced by ALT or AST > 3x upper limit of the normal range
- Allergy or hypersensitivity to any of the active IMPs, or to any of the excipients used
- Pregnant, trying to conceive, unwilling to use contraception or breastfeeding
Current participation in another interventional prophylactic or vaccine trial* against COVID-19.
- Patients remain eligible for enrolment if they have received SARS-COV-2 vaccination as part of routine care.
NICLOSAMIDE ARM Additional exclusion criteria
- Significant structural nasal disease in the opinion of the investigator
- Prior participation in the niclosamide arm of the trial (if being re-screened for participation in a second interventional arm).
CICLESONIDE ARM Additional Exclusion Criteria
In addition to the core exclusion criteria in the master protocol, the presence of any of the following will preclude participant inclusion:
- Significant structural nasal disease in the opinion of the investigator
- Prior participation in the ciclesonide arm of the trial (if being re-screened for participation in a second interventional arm).
- Currently taking inhaled corticosteroids - beclometasone dipropionate (aerosol inhaler and dry powder inhaler), budesonide (dry powder inhaler and single-dose units for nebulization), ciclesonide (aerosol inhaler), fluticasone propionate (dry powder inhaler, aerosol inhaler, and single-dose units for nebulization), mometasone furoate (dry powder inhaler).
- Received a live vaccine within last 14 days - ciclesonide increases risk of generalised infection: influenza, MMR, rotavirus, typhoid, varicella-zoster (shingles), yellow fever.
Taking one of the following medications
○ Systemic Ketoconazole, itraconazole, ritanovir, nelfinavir
SOTROVIMAB ARM Additional Inclusion Criteria
• Absent or suboptimal response (Roche Elecsys® Anti-SARS-CoV-2 assay result <400 AU/mL) to COVID-19 vaccination (sub-optimal/absent vaccination response to be confirmed via centralised COVID-19 antibody assay as part of screening visit prior to randomisation; central lab will report the result of the assay to site as either 'positive' or 'negative' using the pre-specified threshold)
AND
• Be a member of an immunocompromised population, which includes but is not limited to those groups listed in the core protocol as well as the following:
- Primary immunodeficiency
- Any Oncology, Haematology-Oncology or Haematology patient who is currently receiving or has received chemotherapy or who is immunocompromised as a result of their disease or treatment
- Have a diagnosis of an autoimmune/inflammatory disease currently receiving immunosuppression including those individuals currently on Prednisolone ≥20mg daily for at least 4 weeks. Those who have received Rituximab or Alemtuzumab within the last 12 months would also be eligible.
- Solid organ and haematopoietic stem cell transplant recipients
Additional Exclusion Criteria
In addition to the core exclusion criteria in the master protocol, the presence of any of the following will preclude participant inclusion:
- Antibody response to COVID-19 vaccination above the pre-specified threshold, as measured by the central laboratory antibody assay
- If in the opinion of the PI it is not in the best interests of the participant to take part in the study - for example due to limited life expectancy (≤12 months) due to pre-existing co-morbidities
- History of hypersensitivity reaction to sotrovimab, one of its excipients or any other monoclonal antibody targeting SARS CoV-2
- History of receiving any monoclonal antibody targeting SARS CoV-2 within the last 6 months
- Admission to hospital for acute, unplanned care at the time of randomisation or in the two weeks prior to screening
- History of receiving chimeric antigen receptor T-cell (CAR-T) therapy less than 4 weeks prior to consenting to take part in the study
Sites / Locations
- Cambridge University Hospitals NHS Foundation TrustRecruiting
- University Hospitals Birmingham NHS Foundation TrustRecruiting
- Betsi Cadwaladr University Health BoardRecruiting
- Brighton and Sussex University Hospitals NHS TrustRecruiting
- North Bristol NHS TrustRecruiting
- East Kent Hospitals University NHS Foundation TrustRecruiting
- Cardiff & Vale University Health BoardRecruiting
- Epsom and St Helier University Hospitals NHS TrustRecruiting
- Ayrshire & Arran NHS TrustRecruiting
- Dartford and Gravesham NHS TrustRecruiting
- University Hospitals of Derby and Burton NHS TrustRecruiting
- Dorset County Hospital NHS Foundation TrustRecruiting
- NHS TaysideRecruiting
- The Royal Devon and Exeter NHS Foundation TrustRecruiting
- James Paget University Hospital NHS Foundation TrustRecruiting
- Hull University Teaching Hospitals NHS TrustRecruiting
- Queen Elizabeth Hospital, King's Lynn, NHS Foundation TrustRecruiting
- University Hospitals of Leicester NHS TrustRecruiting
- Royal Liverpool and Broadgreen University Hospitals NHS TrustRecruiting
- Barts Health NHS TrustRecruiting
- Guy's and St Thomas' NHS Foundation TrustRecruiting
- Imperial College Healthcare NHS TrustRecruiting
- King's College Hospital NHS Foundation TrustRecruiting
- Royal Free NHS Foundation TrustRecruiting
- St George's University Hospitals NHS Foundation TrustRecruiting
- Nottingham University Hospitals NHS TrustRecruiting
- Oxford University Hospitals NHS Foundation TrustRecruiting
- Royal Berkshire NHS FoundationRecruiting
- Salford Royal NHS FoundationRecruiting
- Sheffield Teaching Hospitals NHS Foundation TrustRecruiting
- East and North Hertfordshire NHS TrustRecruiting
- South Tyneside and Sunderland NHS Foundation TrustRecruiting
- Wirral University Teaching Hospital NHS Foundation TrustRecruiting
- The Royal Wolverhampton NHS TrustRecruiting
- York Teaching Hospital NHS Foundation TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Active Comparator
Placebo Comparator
Active Comparator
Placebo Comparator
Experimental
Placebo Comparator
Niclosamide
Placebo niclosamide
Ciclesonide
Placebo ciclesonide
Sotrovimab
Placebo sotrovimab
INN: Niclosamide Ethanolamine Chemical name (IUPAC): 5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide.2 aminoethanol CAS registry number: 1420-04-8 Lab code: UNI911 The IMPs niclosamide Nasal Spray 1% and matching Nasal Spray Placebo will be provided in 20 mL amber glass vials with nasal spray pumps, containing 8.5 mL of the respective solution, delivering 140 μL per spray shot. It is an isotonic and euhydric aqueous solution with red colour.
Placebo to match niclosamide will be supplied, stored, labelled, dispensed and dosed as for the active formulation. The placebo product is formulated to have the same appearance as the active solution.
Chemical name (IUPAC): 2-[(1S,2S,4R,8S,9S,11S,12S,13R)-6-cyclohexyl-11-hydroxy-9,13-dimethyl-16-oxo-5,7-dioxapentacycloicosa-14, 17-dien-8-yl]- 2-oxoethyl 2-methylpropanoate CAS registry number: 141845-82-1 It is a pressurised solution, intended for inhalation use and commercialised under the brand Alvesco. The recommended dose of ciclesonide is 160μg once daily, which leads to asthma control in the majority of patients. However, this may be increased if necessary to 320μg twice daily, in severe asthma.
Matched placebo contains the same solvent and propellant as the active product but no drug substance.
Sotrovimab, VIR-7831, GSK4182136 Sterile solution for intravenous infusion, 62.5 mg/mL, intravenous infusion Colourless or yellow to brown, liquid solution 20 mM histidine, 7% sucrose (w/v), 0.04% PS80 (w/v), 5 mM L-methionine at pH 6.0
This will be in the form of 0.9% sodium chloride 50mL for infusion and will be sourced from commercially available stock by the site. It may be procured and stored as per sites usual procedures and only requires handling as an IMP upon dispensing and labelling.