Patients with immunosuppressive conditions who are highly vulnerable to COVID-19 (SARS-CoV-2 infection) and have one of the following diseases: haematological malignancies, solid tumours, renal and hepatic disorders, inflammatory disease Infections and Infestations
Conditions
Interventions
All the participants in the study will receive a 600 mg single dose of AZD7442 administered intramuscularly into the upper arm at the time of registration. Participants will then be randomised using a
Sponsors
Cardiff University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent 2. Previous completed SARS-CoV-2 vaccinations given as part of standard care at the time of enrolment 3. Able and willing (in the Investigator’s opinion) to comply with all trial requirements 4. Willingness to practice continuous effective contraception during the first 3 months of the trial and if appropriate, a negative pregnancy test on the day of screening 5. Provide access to all medical records with respect to current and past medical treatments 6. Have one or more of the eligible conditions specified in the protocol (haematological malignancies, solid tumours, renal and hepatic disorders, inflammatory disease) 7. Adults =18 years
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 18/11/2022: 1. Significant infection or other acute illness, including fever >100°F (>37.8°C) on the day prior to or day of screening 2. Prognosis of fewer than 6 months 3. Eastern Cooperative Oncology Group (ECOG) Performance status of >2 4. Planned receipt of any vaccine other than the trial intervention within 30 days before and after each trial intervention (day 0 and day 28) with the exception of the seasonal influenza vaccination, and non-COVID vaccinations in the case of patients receiving a haemopoietic stem cell transplant 5. History of reactions likely to be exacerbated by any component of AZD7442 and SARS-CoV2 vaccine 6. Anaphylactic reaction following administration of a vaccine 7. Known history of allergy or reaction to any component of the trial drug formulation 8. Patients who are pregnant or lactating at trial entry or planning to become pregnant within 3 months after AZD7442 administration 9. Previous hypersensitivity, clinically significant infusion-related reaction, or severe adverse reaction following administration of a mAb 10. Any prior receipt of other mAb indicated for the prevention or treatment of SARS-CoV-2 or COVID-19 11. Clinically significant bleeding disorder (in the opinion of the investigator e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture 12. Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the trial, affect the ability of the participant to participate in the trial, or impair interpretation of the trial data 13. Receipt of any IMP in the preceding 90 days or expected receipt of IMP during the period of trial follow-up, or concurrent participation in another interventional trial unless IMP is essential to clinical care 14. Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to randomization 15. A history of hypersensitivity reactions including anaphylaxis and angioedema following administration of a COVID-19 vaccine 16. A history of thrombocytopenia, including immune thrombocytopenia (ITP) following administration of a COVID-19 vaccine 17. A history of Guillain-Barré Syndrome 18. Patients with acute promyelocytic leukaemia 19. Individuals with a known history of capillary leak syndrome (CLS) _____ Previous exclusion criteria: 1. Significant infection or other acute illness, including fever >100°F (>37.8°C) on the day prior to or day of screening 2. Prognosis of fewer than 6 months 3. Eastern Cooperative Oncology Group (ECOG) Performance status of >2 4. Planned receipt of any vaccine other than the trial intervention within 30 days before and after each trial intervention (day 0 and day 28) with the exception of the seasonal influenza vaccination, and non-COVID vaccinations in the case of patients receiving a haemopoietic stem cell transplant 5. History of reactions likely to be exacerbated by any component of AZD7442 and SARS-CoV2 vaccine 6. History of laboratory-confirmed SARS-COV-2 within the last 3 months 7. Anaphylactic reaction following administration of a vaccine 8. Known history of allergy or reaction to any component of the trial drug formulation 9. Patients who are pregnant or lactating at trial entry or planning to become pregnant within 3 months after AZD7442 administration 10. Previous hypersensitivity, clinically signific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The pharmacokinetics of AZD7442 will be assessed using serum samples taken on Day 0 (Predose AZD7442), and days 28, 112, 180, 273 and 364 post AZD7442 treatment 2. Safety and tolerability of a single IM dose of AZD7442 followed by a SARS-CoV2 vaccine booster 28 days later, assessed by monitoring the SAE reporting using CTCAE v5.0 throughout the trial 3. Levels of serum spike (S) and the nucleocapsid (N) antigens and specific antibody and T cell responses will be measured from serum samples taken on Day 0 (Predose AZD7442), and days 28, 42, 56, 112, 180, 273 and 364 post AZD7442 treatment to assess humoral and cellular immune response against SARS-CoV-2 variants 4. Levels of SARS-CoV-2 neutralizing antibodies will be measured using serum samples taken on Day 0 (Predose AZD7442) and post AZD7442 treatment to assess the effect of a SARS-CoV-2 vaccine on AZD7442 monoclonal antibody titres | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Incidence of a subset of participants who have a post-treatment response (negative/low at baseline to positive at any time post-baseline) for SARS-CoV-2 nucleocapsid antibodies will be assessed using serum samples taken on Day 0 (Predose AZD7442), and days 28, 112, 180, 273 and 364 post AZD7442 treatment 2. The incidence of SARS-CoV-2 infection in trial participants will be measured by ad-hoc PCR testing in symptomatic patients throughout the trial and by routine (asymptomatic) nasal PCR swabs taken from a subset of participants on Day 0 (Predose AZD7442), and days 28, 112, 180, 273 and 364 post AZD7442 treatment 3. PCR testing of all nasal swabs taken by participants will undergo sequencing to identify SARS-CoV2 variants and potential AZD7442 escape variants at baseline and if they are positive for COVID following dosing with AZD7442 4. Behaviour of trial participants assessed using validated behavioural questionnaires (risk behaviour changes, PROMIS 10, EQ-5D-5L) completed by participants at baseline and on days 112, 180 and 364 5. The humoral and/or T cell responses in participants randomised to receive different SARS-CoV-2 vaccines will be compared using serum samples taken on Day 0 (Predose AZD7442), and days 28, 42, 56, 112, 180, 273 and 364 post AZD7442 treatment 6. Disease severity in participants contracting SARS-CoV-2 within the duration of the trial assessed using the WHO Clinical Progression Scale as and when patients get infections | — |
Countries
England, United Kingdom, Wales
Outcome results
None listed