Evaluating a full or fractional third dose of COVID-19 vaccines in previously vaccinated adults

Phase 4

• Conditions: The administration of fractional dose of Pfizer/Wyeth or AstraZeneca/Fiocruz vaccines for prevention of COVID-19 when used as an additional dose in adults aged 18 years or older who have received 2 doses of Sinovac/Butantan, at least 4 months (120 days) prior to administration of booster.; Infections and Infestations

• Registration Number: ISRCTN47074508
• Lead Sponsor: niversity of Oxford

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-03-17
• Last Update Posted: 28 March 2022
• Study Completion: 2022-12-01

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 700

Inclusion Criteria

1. Males or females aged 18 years old or above.
2. Participants willing and able to comply with the study procedure.
3. Participants willing and able to provide informed consent prior to screening.
4. Participants who received two Sinovac/Butantan vaccine doses at least 4 months (120 days) prior to enrolment in this study, with a dose interval between each Sinovac/Butantan dose of 14-28 days (+ 7 days).
5. For females of childbearing potential: willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of screening and vaccination.

Exclusion Criteria

1. Participants with fever >37.5 °C (axillary) or any acute disease at baseline (Day 1) or within the 3 days prior to randomization. Febrile participants with mild diseases may be enrolled at the investigator’s discretion.
2. Participants with a recent history of COVID-19 (= 4 weeks prior to visit 1), laboratory confirmed.
3. Participants with a history of serious vaccine-related adverse reaction or serious allergic reaction (e.g., anaphylaxis) to any study vaccine component, as described in the last summary of product characteristics for Sinovac/Butantan, AstraZeneca/Fiocruz or Pfizer/Wyeth.
4. Participants with a known bleeding disorder that, in the investigator’s opinion, would contraindicate intramuscular injection.
5. Participants with any progressive or serious neurological disorder, seizure disorder or history of Guillian-Barré syndrome.
6. Participants given treatment with immunosuppressant therapy within the last 90 days, including cytotoxic agents or systemic corticosteroids or planned receipt during the study period. If a short-term cycle of immunosuppressant systemic corticosteroid dose has been used to treat acute disease, the participant should not be enrolled in the study until corticosteroid therapy has been discontinued for at least 15 days prior to the first study vaccination. In case the participant has been on an immunosuppressant dose of a depot, intramuscular or intra-articular corticosteroid, 60 days should be waited for their enrolment in the study. Inhaled/nebulized, intra-articular, intrabursal or topical (skin or eyes) corticosteroids are allowed.
7. Participants with autoimmune diseases, other than: Hashimoto thyroiditis, vitiligo, psoriasis, discoid lupus and the like; HIV-positive participants and/or in treatment for HIV;
8. Participants given any other investigational product within the 30 days prior to Day 1 or who intend to take part in another clinical trial at any time during this study conduction.
9. Participants given any other licensed vaccine within 14 days prior to enrolment in this study or who plan to receive any vaccine up to 28 days after vaccination.
10. Participants given treatment with Rituximab or any other anti-CD20 monoclonal antibody within 9 months prior to Day 1 or planned during the study period.
11. Administration of intravenous immunoglobulins and/or any blood products within 3 months prior to enrolment or planned dosing during the study period.
12. Participants with any condition that, in the investigator’s opinion, could interfere with the status primary objectives or represent an additional risk for the participant.
13. Participants who have received any other vaccine for Covid-19 other than two Sinovac/Butantan doses.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. Sororesponse is measured using anti-Spike IgG seroresponse rate (SRR)* in the fractional and full dose arms. *SRR is defined as: 4-fold rise in GMTs at 28 days post study vaccine from baseline among participants with detectable Ab titers pre-booster; OR detectable Ab titres at 28 days post study vaccine among participants with no pre-dose detectable titres.<br> 2. Safety and reactogenicity are measured using an electronic diary completed by participants in the 7 days following visit 1and up to 28 days if unsolicited adverse events occur. Solicited systemic adverse events include fever, chills, joint pains, muscle pains, fatigue, headache, nausea, and loss of appetite. Occurrence of SAEs and AESIs will be followed throughout the Trial.<br>

Secondary Outcome Measures

Name	Time	Method
<br> 1. Humoral immune response measured using geometric mean titre (GMT) and geometric mean fold rise (GMFR) for binding neutralizing antibody titres at day 0, day 28 and day 182.<br> 2. Humoral immune response measured using seroresponse rate (SRR) based on neutralising antibody titres at day 0, day 28 and day 182.<br> 3. Cellular immune responses measured by ELISpot and ICS (Th1/Th2) at day 0, day 28 and day 182.<br>