Clinical trial NCT05378191: Vaccination With COMIRNATY in Subjects With a VAXZEVRIA First Dose
Official title: 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®
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Covid19
Keywords: heterologous vaccination
Lead sponsor: Instituto de Investigación Hospital Universitario La Paz
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
name: Spanish Clinical Research Network - SCReN
First posted: 2022-05-18
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 14 days after randomization
Secondary outcomes:
measure: 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.
timeFrame: 28 days after randomization
measure: 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.
timeFrame: 3, 6 and 12 months after randomization
measure: 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.
timeFrame: Month 1 - 12
measure: To evaluate the safety of a dose of COMIRNATY in subjects that received a previous single dose of VAXZEVRIA (solicited adverse events)
timeFrame: Day 1-7
measure: To evaluate the safety of a dose of COMIRNATY in subjects that received a previous single dose of VAXZEVRIA (unsolicited adverse events)
timeFrame: Day 1-28
measure: To evaluate the safety of a dose of COMIRNATY in subjects that received a previous single dose of VAXZEVRIA (serious adverse events)
timeFrame: Month 1-12
measure: To evaluate the safety of a dose of COMIRNATY in subjects that received a previous single dose of VAXZEVRIA (Medically-attended adverse events)
timeFrame: Month 1-6
Other outcomes:
measure: To evaluate the relationship between the immune response measured as NAV (Neutralizing antibodies) and antibodies against SARS-CoV-2 spike protein measured by immunoassay.
timeFrame: Month 1-12
Locations:
city: Baracaldo
country: Spain
facility: Hospital Universitario de Cruces
state: Bizkaia
city: Barcelona
country: Spain
facility: Hospital Vall d´Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Instituto de Salud Carlos III
name: Cristobal Belda Iniesta, MD, PhD
role: STUDY_CHAIR
affiliation: Spanish Clinical Research Network - SCReN
name: Jesús Frías Iniesta, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Paz
name: Jose R Arribas, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Garcia-Perez J, Gonzalez-Perez M, Castillo de la Osa M, Borobia AM, Castano L, Bertran MJ, Campins M, Portoles A, Lora D, Bermejo M, Conde P, Hernandez-Gutierrez L, Carcas A, Arana-Arri E, Tortajada M, Fuentes I, Ascaso A, Garcia-Morales MT, Erick de la Torre-Tarazona H, Arribas JR, Imaz-Ayo N, Mellado-Pau E, Agusti A, Perez-Ingidua C, Gomez de la Camara A, Ochando J, Belda-Iniesta C, Frias J, Alcami J, Perez-Olmeda M; CombiVacS study Group. Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study. EClinicalMedicine. 2022 Jul 1;50:101529. doi: 10.1016/j.eclinm.2022.101529. eCollection 2022 Aug.
citation: Borobia AM, Carcas AJ, Perez-Olmeda M, Castano L, Bertran MJ, Garcia-Perez J, Campins M, Portoles A, Gonzalez-Perez M, Garcia Morales MT, Arana-Arri E, Aldea M, Diez-Fuertes F, Fuentes I, Ascaso A, Lora D, Imaz-Ayo N, Baron-Mira LE, Agusti A, Perez-Ingidua C, Gomez de la Camara A, Arribas JR, Ochando J, Alcami J, Belda-Iniesta C, Frias J; CombiVacS Study Group. Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet. 2021 Jul 10;398(10295):121-130. doi: 10.1016/S0140-6736(21)01420-3. Epub 2021 Jun 25.