Created at Source Raw Value Validated value
June 25, 2024, noon usa

* 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: 1. significant structural nasal disease in the opinion of the investigator 2. prior participation in the ciclesonide arm of the trial (if being re-screened for participation in a second interventional arm). 3. 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). 4. received a live vaccine within last 14 days - ciclesonide increases risk of generalised infection: influenza, mmr, rotavirus, typhoid, varicella-zoster (shingles), yellow fever. 5. taking one of the following medications ○ systemic ketoconazole, itraconazole, ritanovir, nelfinavir sotrovimab arm additional inclusion criteria • 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: * 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

* 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: 1. significant structural nasal disease in the opinion of the investigator 2. prior participation in the ciclesonide arm of the trial (if being re-screened for participation in a second interventional arm). 3. 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). 4. received a live vaccine within last 14 days - ciclesonide increases risk of generalised infection: influenza, mmr, rotavirus, typhoid, varicella-zoster (shingles), yellow fever. 5. taking one of the following medications ○ systemic ketoconazole, itraconazole, ritanovir, nelfinavir sotrovimab arm additional inclusion criteria • 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: * 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

March 19, 2024, 4 p.m. usa

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 • 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: 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

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 • 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: 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

March 12, 2022, midnight usa

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

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

May 5, 2021, 11:25 a.m. usa

- 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 to niclosamide or history of significant adverse reaction to niclosamide or related compounds, or to any of the excipients used - significant structural nasal disease in the opinion of the investigator - pregnant, trying to conceive, unwilling to use contraception or breastfeeding - 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.

- 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 to niclosamide or history of significant adverse reaction to niclosamide or related compounds, or to any of the excipients used - significant structural nasal disease in the opinion of the investigator - pregnant, trying to conceive, unwilling to use contraception or breastfeeding - 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.