Open-label, Multi-centre, Non-Inferiority study of safety and immunogenicity of BIMERVAX as heterologous booster for the prevention of coronavirus disease 2019 (COVID-19) in adolescents from 12 years to less than 18 years of age.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hipra Scientific S.L.

Participant type

Pediatric, Healthy volunteers

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

26 May 2023 → 9 Sep 2025

Decision date (initial)

2023-05-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

HIPRA SCIENTIFIC S.L.U

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

- To determine and compare the changes in immunogenicity measured by Pseudovirus Based Neutralisation Assay (PBNA) against Omicron BA.1 variant at Baseline and Day 14, after vaccination of adolescents with a heterologous booster dose of BIMERVAX® versus post heterologous booster dose in young adults (aged 18 to 25 years) from the adult booster study (HIPRA-HH-2 EudraCT 2021-005226-26).
- To assess the safety and tolerability of BIMERVAX® as a heterologous booster dose in adolescents primary vaccinated against COVID-19 with 2 doses of Comirnaty vaccine.

Secondary objectives 7

1. To determine the changes in immunogenicity measured by PBNA against Variants of Concern (VOCs) (at least Beta and Delta) at Baseline and at Days 14, 84, 168 and 336 after vaccination of adolescents with a heterologous booster dose of BIMERVAX®.
2. To determine the changes in immunogenicity analysing the Geometric Mean Fold Rise (GMFR) measured by PBNA against Omicron BA.1 and VOCs (at least Beta and Delta) at Baseline and Day 14.
3. To determine the changes in immunogenicity measured by PBNA against Omicron BA.1 variant at Days 84, 168 and 336 after vaccination of adolescents with a heterologous booster dose of BIMERVAX®.
4. To determine the immunogenicity measured by means of total antibody against RBD of the Spike protein of SARS-CoV-2 quantification, measured by electrochemiluminescence immunoassay (ECLIA) at Baseline, Day 14, 84, 168 and 336 after vaccination of adolescents with a heterologous booster dose of BIMERVAX®.
5. To determine the changes in immunogenicity measured by PBNA against Wuhan strain at Baseline and Days 14, 84, 168 and 336 after vaccination of adolescents with a heterologous booster dose of BIMERVAX®.
6. To assess T-cell mediated responses against the SARS-CoV-2 S glycoprotein at Baseline and Day 14 after vaccination of adolescents with a heterologous booster dose of BIMERVAX®. T-cell mediated responses will be performed in a subset of approximately 10% of adolescents and in selected study sites.
7. To assess CD4+ and CD8+ T-cell responses against the SARS-CoV-2 S glycoprotein at Baseline and Day 14 after vaccination of adolescents with a heterologous booster dose of BIMERVAX®. T-cell mediated responses will be performed in a subset of approximately 10% of adolescents and in selected study sites.

Conditions and MedDRA coding

SARS-CoV-2 infection

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003191-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Adolescents aged from 12 to less than 18 years at Screening.
2. Participant’s parent(s)/legal guardian(s) willing and able to sign the informed consent and can comply with all study visits and procedures. A written assent will be required for all participants in the study.
3. Participant must have received two previous doses of Comirnaty, last dose being at least 6 months before screening.
4. Participant has a body mass index at or above the third percentile according to local Child Growth Standards at Screening Visit.
5. Healthy participants and participants with pre-existing, chronic and stable diseases (non-immunocompromised), if these are stable and well-controlled according to the investigator’s judgment, are eligible for inclusion in the study.
6. Has a negative Rapid Antigen Test (RAT) at Day 0 before BIMERVAX® vaccine administration.
7. Participants biologically able to have children may be enrolled in the study if the participant fulfils all the following criteria: a. Has a negative urine pregnancy test at Screening (Day 0), only for those participants who are biologically able to become pregnant. b. Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the booster dose, only for those participants who are biologically able to become pregnant. c. Has agreed to continue adequate contraception or abstinence through 3 months following the booster dose.
8. Participant must have a body weight >50 kg at Screening visit to be eligible for the cellular immunology assays.

Exclusion criteria 15

1. Acute illness with fever ≥ 38.0°C at Screening or within 24 hours prior to vaccination. Participant can be rescheduled for Screening when they have completed 24 hours without fever. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator.
2. Received medications intended to prevent or treat COVID-19 before Screening, except for Comirnaty vaccines.
3. Previous or current diagnosis of MIS-C.
4. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
5. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of the study intervention(s).
6. Immunocompromised individuals defined as those with primary and secondary immune deficiencies and those receiving chemotherapy or immunosuppressant drugs other than steroids and glucocorticoids (maximum 1 mg/kg/day of prednisone or total dose of 20mg/day by any administration route for a maximum of 30 consecutive days), within 90 days prior to vaccination or during the study.
7. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
8. Female who is pregnant or breastfeeding.
9. Receipt of blood/plasma products, immunoglobulin, monoclonal antibodies, or receipt of any passive antibody therapy, within 90 days prior to vaccination or during the study.
10. Participation in other studies involving study intervention within 28 days prior to screening and/or during study participation.
11. Received any non-study vaccine (including seasonal Influenza vaccine) within 14 days before or after screening. For live or attenuated vaccines, 4 weeks before or after screening.
12. History of illegal substance use or alcohol abuse within the past 2 years.
13. History of a diagnosis or other conditions that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety.
14. Individuals who are family members of the Investigators.
15. Individuals with documented medical history of microbiologically confirmed COVID-19 will not be eligible for the immunogenicity group.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Neutralisation titre against Omicron BA.1 measured as inhibitory concentration 50 (IC50) by PBNA and reported as log10 concentration for each individual sample and Geometric Mean Titre (GMT) for group comparison with HIPRA-HH-2 at Baseline and Day 14.
2. Solicited local and systemic reactions through Day 7 after vaccination.
3. Unsolicited local and systemic adverse events (AEs) through Day 28 after vaccination.
4. Related adverse events (AEs) and all serious adverse events (SAEs) through the end of the study.
5. Adverse event of special interest (AESI) through the end of the study.
6. Related medically attended adverse events (MAAE) through the end of the study.
7. Grade 2, Grade 3 and Grade 4 changes from Baseline in safety laboratory parameters through Day 14 after vaccination.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hipra Scientific S.L.

Sponsor organisation

Hipra Scientific S.L.

Address

Avinguda Selva 135

City

Amer

Postcode

17170

Country

Spain

Scientific contact point

Organisation

Hipra Scientific S.L.

Contact name

Teresa Prat

Public contact point

Organisation

Hipra Scientific S.L.

Contact name

Teresa Prat

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications