Assessing Immune Response of Different COVID-19 Vaccines in Older Adults
- Conditions
- Prevention of COVID-19
- Interventions
- Biological: Comirnaty(BTN162b2)Biological: Comirnaty (BTN162b2)Biological: Spikevax (mRNA-1273)
- Registration Number
- NCT05160766
- Lead Sponsor
- Oliver Cornely, MD
- Brief Summary
This is a randomised controlled, adaptive, multicentre Phase II protocol evaluating different booster strategies in individuals aged 75 years and older already vaccinated against SARS-CoV-2.
Part A of this trial foresees testing of different vaccines as a 3rd vaccination dose (first booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants in the elderly, a usually neglected population.
Part B of this trial foresees testing of different vaccines as a 4th vaccination dose (second booster) for comparative assessment of their immunogenicity and safety against SARSCoV-2 wild-type and variants in the identical population.
- Detailed Description
Part A of the present trial in which individuals received a 3rd vaccination (first booster) of either BNT162b2 or mRNA-1273 was closed to further recruitment as of January 13, 2022. This was due to a change in vaccination policies, recommending a 3rd vaccination with either BNT162b2 or mRNA-1273. Therefore, Part A was supplanted by Part B that investigated a 4th COVID-19 vaccination and started on 21 Jan 2022.
The initial study protocol started the trial with Part A in which participants were randomized to a 3rd vaccination (first booster) with either BNT162b2 or mRNA-1273:
Subjects who - prior to study entry - received a vaccination series of either BNT162b2 \& BNT162b2 or mRNA-1273 \& mRNA-1273 or ChAdOx-1-S \& ChAdOx-1-S.
For the reasons mentioned above, the study protocol was amended to continue the trial with Part B in which participants were randomized to a 4th vaccination (second booster) with either BNT162b2 or mRNA-1273:
Subjects who - prior to study entry - received a vaccination series of either BNT162b2 \& BNT162b2 \& BNT162b2 or BNT162b2 \& BNT162b2 \& mRNA-1273 or mRNA-1273 \& mRNA-1273 \& mRNA-1273 or mRNA-1273 \& mRNA-1273 \& BNT162b2 or ChAdOx-1-S \& ChAdOx-1-S \& BNT162b2 or ChAdOx-1-S \& ChAdOx-1-S \& mRNA-1273.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 323
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vaxzevria-Vaxzevria-Spikevax Comirnaty(BTN162b2) Participants are already fully vaccinated with 2x Vaxzevria (ChAdOx-1-S) and 1x Spikevax (mRNA-1273) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Vaxzevria-Vaxzevria-Comirnaty Spikevax (mRNA-1273) Participants are already fully vaccinated with 2x Vaxzevria (ChAdOx-1-S) and 1x Comirnaty (BNT162b2) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Spikevax-Spikevax-Comirnaty Spikevax (mRNA-1273) Participants are already fully vaccinated with 2x Spikevax (mRNA-1273) and 1x Comirnaty (BNT162b2) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Comirnaty-Comirnaty-Spikevax Comirnaty(BTN162b2) Participants are already fully vaccinated with 2x Comirnaty (BNT162b2) and 1x Spikevax (mRNA-1273) entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Comirnaty-Comirnaty-Comirnaty Comirnaty(BTN162b2) Participants are already fully vaccinated with 3x Comirnaty (BNT162b2) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Vaxzevria-Vaxzevria-Spikevax Spikevax (mRNA-1273) Participants are already fully vaccinated with 2x Vaxzevria (ChAdOx-1-S) and 1x Spikevax (mRNA-1273) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Spikevax-Spikevax-Comirnaty Comirnaty(BTN162b2) Participants are already fully vaccinated with 2x Spikevax (mRNA-1273) and 1x Comirnaty (BNT162b2) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Comirnaty-Comirnaty-Spikevax Spikevax (mRNA-1273) Participants are already fully vaccinated with 2x Comirnaty (BNT162b2) and 1x Spikevax (mRNA-1273) entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Comirnaty-Comirnaty-Comirnaty Spikevax (mRNA-1273) Participants are already fully vaccinated with 3x Comirnaty (BNT162b2) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Spikevax-Spikevax-Spikevax Comirnaty(BTN162b2) Participants are already fully vaccinated with 3x Spikevax (mRNA-1273) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Spikevax-Spikevax-Spikevax Spikevax (mRNA-1273) Participants are already fully vaccinated with 3x Spikevax (mRNA-1273) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. Vaxzevria-Vaxzevria-Comirnaty Comirnaty(BTN162b2) Participants are already fully vaccinated with 2x Vaxzevria (ChAdOx-1-S) and 1x Comirnaty (BNT162b2) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial. BNT162b2 (Part A) Comirnaty (BTN162b2) vaccination with BNT162b2 as 3rd vaccination BNT162b2 (Part B) Comirnaty (BTN162b2) vaccination with BNT162b2 as 4th vaccination mRNA-1273 (Part A) Spikevax (mRNA-1273) vaccination with mRNA-1273 as 3rd vaccination mRNA-1273 (Part B) Spikevax (mRNA-1273) vaccination with mRNA-1273 as 4th vaccination
- Primary Outcome Measures
Name Time Method Antibody Titre Increase 14 Days After Study Vaccination Dose. From Day 0 until Day 14 Rate of 2-fold antibody titre increase 14 days after 3rd (Part A) or 4th vaccination dose (Part B) measured by qualitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wildtype virus.
- Secondary Outcome Measures
Name Time Method Change in Neutralizing Antibody Titre Against Wild-type 14 Days After Study Vaccination Dose From Day 0 until Day 14 Change in neutralizing antibody titre (Virus Neutralisation Assay) against wild-type 14 days after a 3rd (Part A) or 4th vaccination dose (Part B), to be determined in a subgroup only.
Microneutralization assay results were proposed to be reported as "change in neutralizing antibody titre (Virus Neutralisation Assay)" in the trial protocol. However, as the pandemic progressed, the need arose to assess neutralization against different variants. In our stud(ies), we evaluated not only the Wuhan strain but also 25 distinct variants of concern (VoCs) and/or variants of interest (VoIs). For VoCs and VoIs, expressing results as "change in neutralization capacity expressed as a percentage (%)" is more effective as it illustrates the impact of mutations on neutralization, thereby allowing cross-variant comparisons. This adjustment did not alter the suggested endpoint, as both reporting methods reflect the ability of patients' antibodies neutralizing capacities.Change in Neutralizing Antibody Titre Against Variants of Concern 14 Days After Study Vaccination Dose From Day 0 until Day 14 Change in neutralizing antibody titre (Virus Neutralisation Assay) against variants of concern 14 days after a 3rd (Part A) or 4th vaccination dose (Part B), to be determined in a subgroup only.
Microneutralization assay results were proposed to be reported as "change in neutralizing antibody titre (Virus Neutralisation Assay)" in the trial protocol. However, as the pandemic progressed, the need arose to assess neutralization against different variants. In our stud(ies), we evaluated not only the Wuhan strain but also 25 distinct variants of concern (VoCs) and/or variants of interest (VoIs). For VoCs and VoIs, expressing results as "change in neutralization capacity expressed as a percentage (%)" is more effective as it illustrates the impact of mutations on neutralization, thereby allowing cross-variant comparisons. This adjustment did not alter the suggested endpoint, as both reporting methods reflect the ability of patients' antibodies neutralizing capacities.Antibody Titre Level at 12 Months After a Study Vaccination Dose From Day 0 until Month 12 Antibody titre level at 12 months after a 3rd (Part A) or 4th vaccination dose (Part B) measured by a quantitative enzyme-linked immunosorbent assay (anti-RBD-ELISA assay).
Neutralizing Antibody Titre Against Wild-type at 12 Months After Study Vaccination Dose From Day 0 until Month 12 Neutralizing antibody titre (Virus Neutralisation Assay) against wild-type SARS-CoV-2 at 12 months after a 3rd (Part A) or 4th vaccination dose (Part B), to be determined in a subgroup only.
Microneutralization assay results were proposed to be reported as "change in neutralizing antibody titre (Virus Neutralisation Assay)" in the trial protocol. However, as the pandemic progressed, the need arose to assess neutralization against different variants. In our stud(ies), we evaluated not only the Wuhan strain but also 25 distinct variants of concern (VoCs) and/or variants of interest (VoIs). For VoCs and VoIs, expressing results as "change in neutralization capacity expressed as a percentage (%)" is more effective as it illustrates the impact of mutations on neutralization, thereby allowing cross-variant comparisons. This adjustment did not alter the suggested endpoint, as both reporting methods reflect the ability of patients' antibodies neutralizing capacities.Neutralizing Antibody Titre Against Variants of Concern at 12 Months After Study Vaccination Dose From Day 0 until Month 12 Neutralizing antibody titre (Virus Neutralisation Assay) against variants of concern at 12 months after a 3rd (Part A) or 4th vaccination dose (Part B), to be determined in a subgroup only.
Microneutralization assay results were proposed to be reported as "change in neutralizing antibody titre (Virus Neutralisation Assay)" in the trial protocol. However, as the pandemic progressed, the need arose to assess neutralization against different variants. In our stud(ies), we evaluated not only the Wuhan strain but also 25 distinct variants of concern (VoCs) and/or variants of interest (VoIs). For VoCs and VoIs, expressing results as "change in neutralization capacity expressed as a percentage (%)" is more effective as it illustrates the impact of mutations on neutralization, thereby allowing cross-variant comparisons. This adjustment did not alter the suggested endpoint, as both reporting methods reflect the ability of patients' antibodies neutralizing capacities.
Trial Locations
- Locations (9)
University Hospital Frankfurt
🇩🇪Frankfurt, Germany
Hannover Medical School Hospital
🇩🇪Hannover, Germany
University Hospital Cologne
🇩🇪Cologne, Germany
Reina Sofia University Hospital
🇪🇸Córdoba, Spain
La Paz University Hospital
🇪🇸Madrid, Spain
Biodonostia Health Research Institute
🇪🇸San Sebastián, Spain
Vilnius University Hospital Santaros Klinikos
🇱🇹Vilnius, Lithuania
Helse Bergen HF, Haukeland University Hospital
🇳🇴Bergen, Norway
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Spain