Study to Evaluate the Immunogenicity and Safety of Heterologous SARS-CoV-2 Vaccine Schemes in an Elderly Population

NCT ID: NCT04983537

Last Updated: 2021-07-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-26

Study Completion Date

2021-09-26

Brief Summary

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To determine whether a heterologous vaccination regimen in individuals with no known previous history of COVID-19 is non-inferior to that observed with counterpart regimens currently in use in Argentina among a population of persons aged 66 or above.

Detailed Description

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The Covid-19 disease caused by the SARS-COV 2 virus has caused a pandemic with more than 180 million cases worldwide and more than 4 million deaths. In Argentina, this pandemic has had a significant impact, with about 4.5 million cases and about 95,000 deaths. In no more than nine months, medical science developed different vaccines to prevent new cases and mitigate this pandemic.

At the time of the presentation of this research protocol, there are four vaccines for the prevention of COVID-19 approved for emergency use by the National Administration of Medicines, Food and Medical Technology (ANMAT). Of these, three (1-3) are currently available and are part of the vaccination campaign. Of these three vaccines, two use a non-replicating viral vector platform (Gam-COVID-Vac and ChAdOx1 nCoV-19) while one uses an inactivated virus platform (BBIBP-CorV). All require the administration of two doses with an administration interval of at least 21 days.

All these vaccines were designed to be used with a homologous two-dose regimen. However, for both logistical and biomedical reasons, the need to use vaccines in heterologous regimens (one dose of one vaccine and a second dose of another vaccine) is emerging worldwide. The efficacy and safety of this type of regimen has not yet been demonstrated.

In Argentina, there are a large number of people who currently have one dose of Gam-COVID-Vac vaccine and who - even after a period of ≥21 days - have not received the second component. At the same time, the provision of the second component of the Gam-COVID-Vac vaccine is delayed due to production and distribution logistics.

As of June 2021, among the universe of people vaccinated with Gam-COVID, residents of CABA, vaccinated in establishments in the City of Buenos Aires - and excluding deceased and infected people - there were a total of 325,788 people with one dose and ≥22 and ≤90 days since the first dose was administered. In a context of high viral circulation, it is desirable to try to vaccinate as much of the population as possible with a full schedule in the shortest possible time. In addition, new variants of SARS-COV2 virus possessing the E384K genomic variant such as the gamma strain (formerly Manaus), the beta strain (known as South African) and the Delta strain (also known as Indian) have the ability to evade the immune system and therefore most laboratories that have developed vaccines recognise that the efficacy of the vaccines requires two doses.

The use of heterologous schedules is a source of active research in various parts of the world (4-6). However, most of this research is testing the combination of a combination schedule that includes an mRNA vaccine. There is an ongoing study sponsored by the Gamaleya Institute and AstraZeneca that is evaluating the immunogenicity of a scheme similar to the one proposed in this trial. Results from this joint trial would not be available until mid-October (7). No trials have evaluated the combination of rAd26-rAd5 and BBIBP-CorV.

This study will attempt to determine whether administration of a heterologous regimen combining a first dose of Gam-COVID-Vac with a second dose of ChAdOx1 nCoV-19 or BBIBP-CorV results in non-inferior immunogenicity to the homologous regimen used.

The present protocol is therefore oriented to respond to a practical management need and to guarantee the best possible protection to the population through two doses, which is what is considered worldwide as "complete vaccination" according to WHO for the vaccines used by Argentina. The proposed protocol is a pragmatic and public health oriented clinical trial, whose primary objective is to establish whether there are indicators that allow the implementation of a heterologous vaccination scheme. For this, a surrogate endpoint will be used, which is immunogenicity measured by the presence of antibodies against protein S. In addition, the safety of the combination will be evaluated in terms of monitoring self-reported and non-self-reported clinical events by patients.

Conditions

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COVID-19 Vaccines

Keywords

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COVID-19 Serological Testing

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

SINGLE

Outcome Assessors
All personnel involved in antibody determination shall remain blinded to the assigned strategy.

Study Groups

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Gam-COVID-Vac / Gam-COVID-Vac

Group Type ACTIVE_COMPARATOR

Gam-COVID-Vac / Gam-COVID-Vac

Intervention Type DRUG

A comparison of antibody levels against protein S will be performed using the Gam-COVID-Vac / Gam-COVID-Vac group as a control group and the Gam-COVID-Vac / ChAdOx1 nCoV-19 and Gam-COVID-Vac / BBIBP-CorV groups as comparators.Comparisons will be made by contrasting the geometric means of antibody levels between each of the study arms. In addition, comparisons will be made as to whether or not the median antibody values of the alternative treatment groups are lower than: a) the 25th percentile of the median antibody value of the Gam COVID combination and b) whether the lower limit of the confidence interval of the differences in the GMC rate is lower than the conventional cut-off point of non-inferiority set at 0.67.

Gam-COVID-Vac / ChAdOx1 nCoV-19

Group Type ACTIVE_COMPARATOR

Gam-COVID-Vac / Gam-COVID-Vac

Intervention Type DRUG

A comparison of antibody levels against protein S will be performed using the Gam-COVID-Vac / Gam-COVID-Vac group as a control group and the Gam-COVID-Vac / ChAdOx1 nCoV-19 and Gam-COVID-Vac / BBIBP-CorV groups as comparators.Comparisons will be made by contrasting the geometric means of antibody levels between each of the study arms. In addition, comparisons will be made as to whether or not the median antibody values of the alternative treatment groups are lower than: a) the 25th percentile of the median antibody value of the Gam COVID combination and b) whether the lower limit of the confidence interval of the differences in the GMC rate is lower than the conventional cut-off point of non-inferiority set at 0.67.

Gam-COVID-Vac / BBIBP-CorV

Group Type ACTIVE_COMPARATOR

Gam-COVID-Vac / Gam-COVID-Vac

Intervention Type DRUG

A comparison of antibody levels against protein S will be performed using the Gam-COVID-Vac / Gam-COVID-Vac group as a control group and the Gam-COVID-Vac / ChAdOx1 nCoV-19 and Gam-COVID-Vac / BBIBP-CorV groups as comparators.Comparisons will be made by contrasting the geometric means of antibody levels between each of the study arms. In addition, comparisons will be made as to whether or not the median antibody values of the alternative treatment groups are lower than: a) the 25th percentile of the median antibody value of the Gam COVID combination and b) whether the lower limit of the confidence interval of the differences in the GMC rate is lower than the conventional cut-off point of non-inferiority set at 0.67.

Interventions

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Gam-COVID-Vac / Gam-COVID-Vac

A comparison of antibody levels against protein S will be performed using the Gam-COVID-Vac / Gam-COVID-Vac group as a control group and the Gam-COVID-Vac / ChAdOx1 nCoV-19 and Gam-COVID-Vac / BBIBP-CorV groups as comparators.Comparisons will be made by contrasting the geometric means of antibody levels between each of the study arms. In addition, comparisons will be made as to whether or not the median antibody values of the alternative treatment groups are lower than: a) the 25th percentile of the median antibody value of the Gam COVID combination and b) whether the lower limit of the confidence interval of the differences in the GMC rate is lower than the conventional cut-off point of non-inferiority set at 0.67.

Intervention Type DRUG

Other Intervention Names

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Gam-COVID-Vac / ChAdOx1 nCoV-19 Gam-COVID-Vac / BBIBP-CorV

Eligibility Criteria

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Inclusion Criteria

* Persons who have received a dose of Gam-COVID-Vac more than 30 days and less than 90 days ago.
* Age \> 65 years.
* Both genders.
* Who have voluntarily agreed to participate in the clinical trial and have provided informed consent.

Exclusion Criteria

* Known history of COVID in the 6 months prior to study inclusion.
* Known or suspected immunocompromised status by the study investigator for any cause.
* Use of oral or parenteral corticosteroids in the last 30 days.
* Known history of allergy to any vaccine.
* History of anaphylaxis.
* Pregnant or lactating women.
* Known history of autoimmune diseases.
* Persons under treatment for any neoplastic disease within the last 6 months.
* Any serious illness or condition at the discretion of the study investigator (including but not limited to the presence of chronic obstructive pulmonary disease, heart failure, poorly controlled hypertension, poorly controlled diabetes, renal failure).
* Planned medical procedures within two months of randomisation.
* Previous vaccination within the last 30 days with any vaccine.
* Known participation in an ongoing clinical trial.
* Ongoing acute illness.
* Fever (≥37.8 C) at the time of randomisation.
Minimum Eligible Age

66 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Ministerio de Salud de Ciudad Autónoma de Buenos Aires

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospital Ramos Mejía

Ciudad Autonoma de Buenos Aire, CBA, Argentina

Site Status RECRUITING

Ministerio de Salud de la Ciudad Autónoma de Buenos Aires

Buenos Aires, , Argentina

Site Status RECRUITING

Countries

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Argentina

Central Contacts

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Daniel Ferrante, MD

Role: CONTACT

Phone: 5441233221

Email: [email protected]

Facility Contacts

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Marcelo Losso, MD

Role: primary

Alejandro Macchia, MD

Role: primary

Other Identifiers

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5143_2

Identifier Type: -

Identifier Source: org_study_id