Vaccination With COMIRNATY in Subjects With a VAXZEVRIA First Dose

Study Overview
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Brief Summary
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CombiVacS is a phase 2 randomized, adaptive trial developed to evaluate the immunogenicity of a dose of COMIRNATY after a previous single dose of VAXZEVRIA. A stratification will be made based on the following factors: study site, sex and age. This protocol allows to test the immunogenicity and safety of a heterologous vaccination strategy after a previous single dose of VAXZEVRIA.

Detailed Description
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This is a randomized, non-blinded, controlled, adaptive, multicenter, Phase II study in subjects aged ≥18 years and in good health or stable clinical situation that have received a previous single dose of VAXZEVRIA. Subjects will be randomized to immediately receive or not a dose of COMIRNATY in a ratio of 2:1. If primary analysis at day 14th confirms the starting hypothesis, subjects randomized to no vaccination will be considered for administration of one dose of COMINARTY at day 28th according to Public Health Department of the Ministry of Health recommendations on heterologous vaccination. In case the primary analysis does not confirm the starting hypothesis, subjects will be followed at the time points defined in the flow-chart without administration of COMIRNATY. Other heterologous vaccination strategies could be incorporated if deemed necessary for public health reasons. This could include the use of different vaccination strategies including those already marketed vaccines for comparative assessment of their safety and efficacy on SARS-CoV-2 and its variants.

Official Title
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A Phase 2, Comparative, Randomised, Adaptive Trial to Evaluate the Safety and Immunogenicity of One Dose of Comirnaty® in Subjects That Had Received One Dose of Vaxzevria®

Conditions
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Covid19

Intervention / Treatment
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* Drug: COMIRNATY


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects (18 years old) having received a prime VAXZEVRIA vaccination between 8 and 12 weeks before the screening visit Participants must provide consent indicating that he or she understands the purpose, procedures and potential risks and benefits of the study, and is willing to participate in the study. Subjects in good health or stable clinical situation. Participant is willing and able to adhere to the procedures specified in this protocol. Exclusion Criteria: Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC within 24 hours prior to the planned dose of study vaccine. Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse reactions to COMIRNATY excipients. Subjects with any contraindication to the administration of COMIRNATY, included pregnancy. Subjects with prior documented COVID19 since VAXZEVRIA vaccination. Subjects have symptoms or signs compatible with COVID19. Subjects participating in a clinical trial in the last three months. Any condition or situation precluding or interfering the compliance with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized to immediately receive or not a dose of COMIRNATY in a ratio of 2:1. If primary analysis at 14 days confirms the starting hypothesis, subjects randomized to no vaccination will be considered for administration of one dose of COMINARTY at day 28th according to Public Health Department of the Ministry of Health recommendations on heterologous vaccination.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VACCINATION<br>One standard dose of COMIRNATY in adult subjects (18 years old) having received prior VAXZEVRIA vaccination. | Drug: COMIRNATY<br>* One dose of COMIRNATY<br>* Other names: COVID-19, mRNA vaccine;|
| No Intervention: NO INTERVENTION<br>No vaccination in adult subjects (18 years old) having received prior VAXZEVRIA vaccination. If primary analysis at day 14th confirms the starting hypothesis, subjects randomized to this arm will be considered for administration of one dose of COMINARTY at day 28th according to Public Health Department of the Ministry of Health recommendations on heterologous vaccination. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the humoral immune response against SARS-CoV-2, 14 days after vaccination with COMIRNATY in subjects that received a previous single dose of VAXZEVRIA, as compared with no dosing. | Antibodies against SARS-CoV-2 spike protein. Measure: BAU/mL | 14 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the humoral immune response against SARS-CoV-2, 28 days after vaccination with COMIRNATY in subjects that received a previous single dose of VAXZEVRIA. | Antibodies against SARS-CoV-2 spike protein. Measure: BAU/mL | 28 days after randomization | 
| To assess the long-term (up to 1 year) humoral immune response against SARS-CoV-2 of a dose of COMIRNATY in subjects that received a previous single dose of VAXZEVRIA. | Antibodies against SARS-CoV-2 spike protein (BAU/mL) | 3, 6 and 12 months after randomization | 
| To assess the occurrence of symptomatic molecularly confirmed COVID-19 and severity of COVID-19 signs and symptoms after the administration of a dose of COMIRNATY in subjects that received a prior single dose of VAXZEVRIA. | Number of participants with molecularly confirmed COVID-19 and presence and severity of COVID-19 signs and symptoms as measured by Symptoms of Infection with Coronavirus-19 | Month 1 - 12 | 
| To evaluate the safety of a dose of COMIRNATY in subjects that received a previous single dose of VAXZEVRIA (solicited adverse events) | Number of solicited local and systemic adverse events (AEs) for 7 days after vaccine | Day 1-7 | 
| To evaluate the safety of a dose of COMIRNATY in subjects that received a previous single dose of VAXZEVRIA (unsolicited adverse events) | Number of unsolicited local and systemic adverse events (AEs) for 28 days after vaccine | Day 1-28 | 
| To evaluate the safety of a dose of COMIRNATY in subjects that received a previous single dose of VAXZEVRIA (serious adverse events) | Number of Serious adverse events (SAEs) throughout the study (from randomization until end of the study). | Month 1-12 | 
| To evaluate the safety of a dose of COMIRNATY in subjects that received a previous single dose of VAXZEVRIA (Medically-attended adverse events) | Number of Medically-attended adverse events (MAAEs) from the day of vaccination until 6 months after the last vaccination | Month 1-6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heterologous vaccination