Adult Who Received a First Dose of an mRNA Vaccine (Pfizer-BioNTech or Moderna) and Need to Receive a Second DoseARNCOMBINCT04900467
Compare Immunological Efficacy of a Vaccine Regimen Combining Two Covid19 mRNA Vaccines (Pfizer-BioNTech and Moderna) With That of a Homologous Vaccination of Each Covid19 mRNA Vaccine
A study testing Pfizer and Moderna in people with Adult Who Received a First Dose of an mRNA Vaccine (Pfizer-BioNTech or Moderna) and Need to Receive a Second Dose, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
As part of the COVID 19 vaccine campaign, the two mRNA vaccines, BNT162b2 (COMIRNATY®) and mRNA-1273 COVID-19 vaccine Moderna, are administered in two doses in subjects without a history of SARS-CoV-2 infection . Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Adult Who Received a First Dose of an mRNA Vaccine (Pfizer-BioNTech or Moderna) and Need to Receive a Second Dose
- What is being tested?
- Pfizer and Moderna
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 418 participants
- Where
- 1 siteFrance
- Study dates
- 28 May 2021to Jan 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Having received a first dose of one of the two mRNA vaccines (Pfizer-BioNTech or Moderna) as recommended.
- For whom a 2nd dose of mRNA vaccine is planned within 4 to 6 weeks (according to the recommendations of the HAS and the ANSM).
- Without a history of SARS-CoV-2 infection (negative PCR, negative antigen test or negative chest CT or SARS-CoV-2 serology)
- Healthy or in stable health if pre-existing medical history. Stable health is defined as an existing disease that has not required a significant change in treatment or hospitalisation for worsening in the 3 months prior to inclusion, and for which neither a significant change in treatment or hospitalisation for worsening of the disease is envisaged in the near future
- Able to understand and comply with the research procedures as judged by the investigator
- Informed consent signed by the participant and the investigator.
- Person affiliated to a social security scheme.
Who cannot join
- History of SARS-CoV-2 infection at the inclusion visit or between the 2 vaccine doses (documented by positive PCR, positive antigen test or positive chest CT or positive SARS-CoV-2 serology.
- Acute febrile infection (body temperature ≥ 38.0°C) within the previous 72 hours and/or with symptoms suggestive of COVID-19 or case contact within the last 14 days prior to the inclusion visit. Sick or febrile subjects may be re-invited for a new inclusion visit during the inclusion period when they no longer have these symptoms)
- Immunosuppressive medications such as corticosteroids at a dosage > 10 mg prednisone equivalent/day (excluding topical preparations and inhalers) within 3 months prior to inclusion or within 6 months for chemotherapy.
- Treatment with immunoglobulin or other blood product within 3 months prior to inclusion or with planned administration of immunoglobulin or blood product before the end of the study.
- Known HIV, HCV or HBV infection.
- Any immunosuppressive condition, such as cancer, that may reduce the immune response.
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- The use of experimental Ig, experimental monoclonal antibodies or convalescent serum is not permitted during the study.
- Pregnant or breastfeeding.
- Participation in any other research involving humans (Jardé 1 or Jardé 2) within 4 weeks prior to the inclusion visit
- Person subject to a legal protection measure (guardianship, curatorship or safeguard measure).
- History of severe adverse reactions after vaccine administration including anaphylactic reaction and associated symptoms such as rash, difficulty breathing, angiodema and abdominal pain, or a history of allergic reaction that may be exacerbated by a component of the SARS-COV-2 vaccine at the time of the first vaccine injection
- Participant who has been vaccinated against BCG in the previous year.
- Having received a vaccination within 4 weeks prior to the first injection or scheduled to receive a licensed vaccine 4 weeks after the last injection.
- History of severe allergic manifestations
- Any bleeding disorder considered to be a contraindication to intramuscular injection or having had a phlebotomy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multicenter, Randomized, Open-label Trial Comparing the Immunological Efficacy of a Vaccine Regimen Combining Two Covid19 mRNA Vaccines (Pfizer-BioNTech and Moderna) With That of a Homologous Vaccination of Each Covid19 mRNA Vaccine: Non-inferiority Trial
As part of the COVID 19 vaccine campaign, the two mRNA vaccines, BNT162b2 (COMIRNATY®) and mRNA-1273 COVID-19 vaccine Moderna, are administered in two doses in subjects without a history of SARS-CoV-2 infection . In accordance with the marketing authorization for vaccines, HAS recommends that subjects who have received one dose of an mRNA vaccine receive a second dose of the same vaccine with an interval between the 2 doses of 4 to 6 weeks. These two vaccines are based on very similar technologies but were developed independently. Given the similarities between these two vaccines, the choice between the two, for the moment, is based solely on the availability of doses and on logistical constraints. Since April 14, the interval between the two doses of the mRNA vaccines is 42 days.
WHO has announced that in the absence of available data, vaccine interchangeability cannot be recommended. However, to facilitate the organization of the vaccination campaign and allow faster vaccination of the population, it would be desirable to be able to use either one or the other mRNA vaccine for the 2nd dose.
In order to be able to recommend the interchangeability of the 2 mRNA vaccines, it is proposed to evaluate the immunogenicity of a scheme combining the two Covid 19 mRNA vaccines (i.e. a 2nd dose of vaccine with the Moderna vaccine after a first dose of the Pfizer vaccine or 2nd dose of Pfizer vaccine after a first dose of Moderna vaccine) compared to that of a standard vaccination schedule with two doses of the same Covid 19 mRNA vaccine.
Read the detailed description
Covid 19 has infected more than 132 million people around the world (https://covid19.who.int/, data from 04/07/21). In record time, effective vaccines were developed allowing the start of the vaccination campaign less than a year after the outbreak was declared by WHO.
To date, more than 604 million vaccine doses have been administered worldwide (https://covid19.who.int/, data from 04/07/21).
On December 21, 2020, the first mRNA vaccine developed by Pfizer and BioNTech obtained a marketing authorization (conditional AMM) in Europe for the active immunization of people 16 years of age and over to prevent Covid-19 due to SARS -CoV-2. Then, on January 6, 2021 Moderna in turn obtained a conditional Marketing Authorization for the indication of active immunization to prevent Covid-19 due to SARS-CoV-2 in subjects 18 years of age and over.
In France, more than 7 million injections have been performed with the Pfizer / BioNTech vaccine and more than 617,000 doses of the Moderna vaccine.
The two mRNA vaccines, BNT162b2 (COMIRNATY®) from Pfizer / BioNTech and mRNA-1273 COVID-19 vaccine Moderna, are given on a two-dose schedule in subjects without a history of SARS-CoV-2 infection. In accordance with the AMM for vaccines, HAS recommends that subjects who have received one dose of an mRNA vaccine receive a second dose of the same vaccine. The recommended interval between the 2 doses is 4 to 6 weeks. These two vaccines are based on very similar technologies but were developed independently. Given the similarities between these two vaccines, the choice between the two, for the moment, is based solely on the availability of doses and on logistical constraints.
Since 14 April, the interval between the two doses of mRNA vaccines is 42 days. In order to facilitate the organisation of the vaccination campaign and to enable the population to be vaccinated more quickly, it would seem desirable to be able to use either COVID 19 RNA vaccine for the 2nd vaccine dose. However, the WHO has announced that, in the absence of available data, the interchangeability of vaccines cannot be recommended.
In order to be able to recommend the interchangeability of the 2 mRNA vaccines, the ARN Combi trial aims to compare the immunogenicity of a standard vaccine regimen (second dose of the same Covid 19 mRNA vaccine) to that of a regimen combining the two Covid 19 mRNA vaccines (i.e. either a 2nd dose of vaccine with Moderna vaccine after a first dose of Pfizer vaccine or a 2nd dose of Pfizer vaccine after a first dose of Moderna vaccine)
- Being tested
- Pfizer, Moderna
- Keywords
- COVID 19, mRNA vaccines, Immunology, mRNA-1273, BNT162b2
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PfizerBiological
BNT162b2 (Comirnaty®), Pfizer/BioNTech, mARN vaccine,
ModernaBiological
mRNA-1273, COVID-19 Vaccine Moderna, mARN vaccine, administrated by intramuscular
| Study group | Role | What they receive |
|---|---|---|
| Pfizer-Pfizer | Active comparator | Pfizer-Pfizer Length of use : 1 day Receives: Biological: Pfizer |
| Pfizer-Moderna | Experimental | Pfizer-Moderna Length of use : 1 day Receives: Biological: Pfizer; Biological: Moderna |
| Moderna- Moderna | Active comparator | Moderna- Moderna Length of use : 1 day Receives: Biological: Moderna |
| Moderna - Pfizer | Experimental | Moderna - Pfizer Length of use : 1 day Receives: Biological: Pfizer; Biological: Moderna |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti-Spike IgG titer
Anti-Spike IgG titer measured by ELISA and neutralising antibodies to European SARS-CoV-2 and SARS-CoV-2 variants 28 days after the second injection.
Measured: 28 days
Secondary outcomes (1)
Adverse events
Any adverse events, local and systemic reactions occurring up to 180 days (6 months) after the second injection.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2021
- Study start28 May 2021
- Primary completion2 Jul 2021
- Study completionJan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult Who Received a First Dose of an mRNA Vaccine (Pfizer-BioNTech or Moderna) and Need to Receive a Second DoseStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 418 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- COVIREIVAC
- Responsible party
- Sponsor
- Investigators
- Odile LAUNAY, Principal investigator, Assistance Publique - Hôpitaux de ParisCécile JANSSEN, Principal investigator, Centre Hospitalier Annecy Genevois
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04900467
- Sponsor's protocol ID
- APHP210605
- Other IDs
- 2021-002174-52
- Acronym
- ARNCOMBI
- Status last verified
- Jul 2021
- First submitted
- 21 May 2021
- Last updated
- 3 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Janssen C, Cachanado M, Ninove L, Lachatre M, Michon J, Epaulard O, Maakaroun-Vermesse Z, Chidiac C, Laviolle B, Aumaitre H, Assaf A, Lacombe K, Schmidt-Mutter C, Botelho-Nevers E, Briere M, Boisson T, Loubet P, Bienvenu B, Bouchaud O, Touati A, Pereira C, Rousseau A, Berard L, Montil M, de Lamballerie X, Simon T, Launay O; ARNCOMBI Study Group. Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial. EClinicalMedicine. 2022 Jun;48:101444. doi: 10.1016/j.eclinm.2022.101444. Epub 2022 May 12.
PubMed 35582124
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Randomized, Open-label Trial Comparing the Immunological Efficacy of a Vaccine Regimen Combining Two Covid19 mRNA Vaccines (Pfizer-BioNTech and Moderna) With That of a Homologous Vaccination of Each Covid19 mRNA Vaccine: Non-inferiority Trial
- ClinicalTrials.gov ID
- NCT04900467
- Acronym / sponsor ID
- ARNCOMBI / APHP210605
- Keywords
- COVID 19, mRNA vaccines, Immunology, mRNA-1273, BNT162b2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 418 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- COVIREIVAC
- Study start
- 28 May 2021 (actual)
- Primary completion
- 2 Jul 2021 (actual)
- Study completion
- Jan 2022 (estimated)
- First posted
- 25 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
As part of the COVID 19 vaccine campaign, the two mRNA vaccines, BNT162b2 (COMIRNATY®) and mRNA-1273 COVID-19 vaccine Moderna, are administered in two doses in subjects without a history of SARS-CoV-2 infection . In accordance with the marketing authorization for vaccines, HAS recommends that subjects who have received one dose of an mRNA vaccine receive a second dose of the same vaccine with an interval between the 2 doses of 4 to 6 weeks. These two vaccines are based on very similar technologies but were developed independently. Given the similarities between these two vaccines, the choice between the two, for the moment, is based solely on the availability of doses and on logistical constraints. Since April 14, the interval between the two doses of the mRNA vaccines is 42 days.
WHO has announced that in the absence of available data, vaccine interchangeability cannot be recommended. However, to facilitate the organization of the vaccination campaign and allow faster vaccination of the population, it would be desirable to be able to use either one or the other mRNA vaccine for the 2nd dose.
In order to be able to recommend the interchangeability of the 2 mRNA vaccines, it is proposed to evaluate the immunogenicity of a scheme combining the two Covid 19 mRNA vaccines (i.e. a 2nd dose of vaccine with the Moderna vaccine after a first dose of the Pfizer vaccine or 2nd dose of Pfizer vaccine after a first dose of Moderna vaccine) compared to that of a standard vaccination schedule with two doses of the same Covid 19 mRNA vaccine.
Detailed description
Covid 19 has infected more than 132 million people around the world (https://covid19.who.int/, data from 04/07/21). In record time, effective vaccines were developed allowing the start of the vaccination campaign less than a year after the outbreak was declared by WHO.
To date, more than 604 million vaccine doses have been administered worldwide (https://covid19.who.int/, data from 04/07/21).
On December 21, 2020, the first mRNA vaccine developed by Pfizer and BioNTech obtained a marketing authorization (conditional AMM) in Europe for the active immunization of people 16 years of age and over to prevent Covid-19 due to SARS -CoV-2. Then, on January 6, 2021 Moderna in turn obtained a conditional Marketing Authorization for the indication of active immunization to prevent Covid-19 due to SARS-CoV-2 in subjects 18 years of age and over.
In France, more than 7 million injections have been performed with the Pfizer / BioNTech vaccine and more than 617,000 doses of the Moderna vaccine.
The two mRNA vaccines, BNT162b2 (COMIRNATY®) from Pfizer / BioNTech and mRNA-1273 COVID-19 vaccine Moderna, are given on a two-dose schedule in subjects without a history of SARS-CoV-2 infection. In accordance with the AMM for vaccines, HAS recommends that subjects who have received one dose of an mRNA vaccine receive a second dose of the same vaccine. The recommended interval between the 2 doses is 4 to 6 weeks. These two vaccines are based on very similar technologies but were developed independently. Given the similarities between these two vaccines, the choice between the two, for the moment, is based solely on the availability of doses and on logistical constraints.
Since 14 April, the interval between the two doses of mRNA vaccines is 42 days. In order to facilitate the organisation of the vaccination campaign and to enable the population to be vaccinated more quickly, it would seem desirable to be able to use either COVID 19 RNA vaccine for the 2nd vaccine dose. However, the WHO has announced that, in the absence of available data, the interchangeability of vaccines cannot be recommended.
In order to be able to recommend the interchangeability of the 2 mRNA vaccines, the ARN Combi trial aims to compare the immunogenicity of a standard vaccine regimen (second dose of the same Covid 19 mRNA vaccine) to that of a regimen combining the two Covid 19 mRNA vaccines (i.e. either a 2nd dose of vaccine with Moderna vaccine after a first dose of Pfizer vaccine or a 2nd dose of Pfizer vaccine after a first dose of Moderna vaccine)
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Pfizer-Pfizer | Active comparator | Biological: PfizerPfizer-Pfizer Length of use : 1 day |
| Pfizer-Moderna | Experimental | Biological: Pfizer, Biological: ModernaPfizer-Moderna Length of use : 1 day |
| Moderna- Moderna | Active comparator | Biological: ModernaModerna- Moderna Length of use : 1 day |
| Moderna - Pfizer | Experimental | Biological: Pfizer, Biological: ModernaModerna - Pfizer Length of use : 1 day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years
- Having received a first dose of one of the two mRNA vaccines (Pfizer-BioNTech or Moderna) as recommended.
- For whom a 2nd dose of mRNA vaccine is planned within 4 to 6 weeks (according to the recommendations of the HAS and the ANSM).
- Without a history of SARS-CoV-2 infection (negative PCR, negative antigen test or negative chest CT or SARS-CoV-2 serology)
- Healthy or in stable health if pre-existing medical history. Stable health is defined as an existing disease that has not required a significant change in treatment or hospitalisation for worsening in the 3 months prior to inclusion, and for which neither a significant change in treatment or hospitalisation for worsening of the disease is envisaged in the near future
Key exclusion criteria (15 listed)
- History of SARS-CoV-2 infection at the inclusion visit or between the 2 vaccine doses (documented by positive PCR, positive antigen test or positive chest CT or positive SARS-CoV-2 serology.
- Acute febrile infection (body temperature ≥ 38.0°C) within the previous 72 hours and/or with symptoms suggestive of COVID-19 or case contact within the last 14 days prior to the inclusion visit. Sick or febrile subjects may be re-invited for a new inclusion visit during the inclusion period when they no longer have these symptoms)
- Immunosuppressive medications such as corticosteroids at a dosage > 10 mg prednisone equivalent/day (excluding topical preparations and inhalers) within 3 months prior to inclusion or within 6 months for chemotherapy.
- Treatment with immunoglobulin or other blood product within 3 months prior to inclusion or with planned administration of immunoglobulin or blood product before the end of the study.
- Known HIV, HCV or HBV infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PfizerBNT162b2 (Comirnaty®), Pfizer/BioNTech, mARN vaccine, | Biological | Moderna - Pfizer, Pfizer-Moderna, Pfizer-Pfizer |
| ModernamRNA-1273, COVID-19 Vaccine Moderna, mARN vaccine, administrated by intramuscular | Biological | Moderna - Pfizer, Moderna- Moderna, Pfizer-Moderna |
Primary outcome
Anti-Spike IgG titer
Time frame: 28 days
Anti-Spike IgG titer measured by ELISA and neutralising antibodies to European SARS-CoV-2 and SARS-CoV-2 variants 28 days after the second injection.
1 secondary outcome
Adverse events
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2021.
- Derived from this study: PubMed 35582124Janssen C, Cachanado M, Ninove L, Lachatre M, Michon J, Epaulard O, Maakaroun-Vermesse Z, Chidiac C, Laviolle B, Aumaitre H, Assaf A, Lacombe K, Schmidt-Mutter C, Botelho-Nevers E, Briere M, Boisson T, Loubet P, Bienvenu B, Bouchaud O, Touati A, Pereira C, Rousseau A, Berard L, Montil M, de Lamballerie X, Simon T, Launay O; ARNCOMBI Study Group. Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial. EClinicalMedicine. 2022 Jun;48:101444. doi: 10.1016/j.eclinm.2022.101444. Epub 2022 May 12.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Odile LAUNAY principal investigator
Assistance Publique - Hôpitaux de Paris
Cécile JANSSEN principal investigator
Centre Hospitalier Annecy Genevois
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pfizer and Moderna in people with Adult Who Received a First Dose of an mRNA Vaccine (Pfizer-BioNTech or Moderna) and Need to Receive a Second Dose, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anti-Spike IgG titer (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04900467, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2021; AzTrials last refreshed its copy on 8 Nov 2026.