A Phase IIb/III, Double-Blind, Randomised, Active-Controlled, Multi-Center, Non-Inferiority Clinical Trial, to assess the safety and immunogenicity of a booster vaccination with an adapted recombinant protein RBD fusion homodimer candidate (PHH-1V81) against SARS-CoV-2, in adults vaccinated against COVID-19.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hipra Scientific S.L., Hipra Scientific S.L.

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

13 Nov 2023 → 17 Jun 2024

Decision date (initial)

2023-11-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

1. To assess the safety and tolerability of a PHH-1V81 booster in adults who previously received primary vaccination and at least one booster dose of an EU-approved mRNA vaccine.
2. To determine and compare the changes in immunogenicity measured by pseudovirus neutralisation assay (PBNA) against Omicron XBB.1.16 variant at Baseline and Day 14 in the PHH-1V81 vaccine arm versus the Comirnaty arm.

Secondary objectives 5

1. To determine and compare the changes in immunogenicity measured by PBNA against Wuhan, Omicron BA.1 and Omicron XBB.1.5 at Baseline and at Days 14, 91 and 182, and Omicron XBB.1.16 at Days 91 and 182, after vaccination in the PHH-1V81 vaccine arm vs. the Comirnaty arm.
2. To evaluate and compare the immunogenicity measured by means of total antibody against Receptor Binding Domain of the Spike protein of SARS-CoV-2, measured by an electrochemiluminescence immunoassay (ECLIA) at Baseline and at Days 14, 91 and 182 in the PHH-1V81 vaccine arm vs the Comirnaty arm.
3. To assess the number of adults with SARS-CoV-2 infections ≥14 days in both vaccine arms.
4. To assess the number of COVID-19 severe infections ≥14 days in both vaccine arms.
5. To evaluate T-cell mediated responses against the SARS-CoV-2 S glycoprotein at Baseline and at Day 14 for descriptive analysis in a subset of participants from both vaccine arms.

Conditions and MedDRA coding

COVID-19 disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adults aged 18 or older at Day 0.
2. Are willing and able to sign the informed consent and can comply with all study visits and procedures.
3. Participant must have received a primary scheme of an EU-approved mRNA vaccine (2 doses) and at least one booster dose with an EU-approved mRNA vaccine. Last booster dose must have been administered at least 6 months before Day 0.
4. Having a negative Rapid Antigen Test for COVID-19 at Day 0 prior to vaccination.
5. Adults determined by clinical assessment, including medical history and clinical judgement, to be eligible for the study, including adults with pre-existing chronic and stable diseases (non-immunocompromised), if these are stable and well-controlled according to the investigator’s judgment.
6. Participants biologically able to have children may be enrolled in the study if the participant fulfils all the following criteria: • Has a negative urine pregnancy test at Day 0, only for those participants who are biologically able to become pregnant. • Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the study treatment, only for those participants who are biologically able to become pregnant. • Has agreed to continue adequate contraception or abstinence through 3 months following the booster dose. - Participants with female reproductive system: i. Hormonal contraception (progestogen-only or combined: oral, injectable or transdermal (patch)) ii. Intrauterine device. iii. Vasectomized partner (the vasectomized partner should be the sole partner for that participant). iv. Condom. - Participants with male reproductive system: i. Vasectomized participants. ii. Agree to use a condom in partners biologically able to become pregnant.

Exclusion criteria 12

1. Acute illness with fever ≥ 38.0°C at Day 0 or within 24 hours prior to vaccination. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator.
2. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Note: This includes both conditions that may increase the risk associated with study intervention administration or a condition that may interfere with the interpretation of study results.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of the study intervention.
4. Immunocompromised individuals defined as those with primary and secondary immune deficiencies and those receiving chemotherapy or immunosuppressant drugs other than steroids and glucocorticoids (maximum 30mg/day of prednisone, or equivalent, by any administration route for a maximum of 30 consecutive days), within 90 days prior to vaccination.
5. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
6. Receipt of blood-derived immune globulins, blood, or blood-derived products in the past 3 months.
7. Participation in other studies involving study intervention if last dose is within 28 days prior to screening and/or it is planned to receive during study participation.
8. Received any non-study vaccine within 14 days before or after screening. For live or attenuated vaccines, 4 weeks before or after screening.
9. Received any COVID-19 vaccines other than EU-approved mRNA vaccines.
10. Received any Omicron XBB adapted vaccine before Day 0.
11. COVID-19 infection diagnosed in the previous 6 months before Day 0. History of COVID-19 infections is allowed.
12. History of a diagnosis or other conditions that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Number, percentage, and characteristics of solicited local and systemic reactions through Day 7 after vaccination.
2. Number, percentage, and characteristics of unsolicited local and systemic adverse events (AEs) through Day 28 after vaccination.
3. Number and percentage of serious adverse events (SAEs) through the end of the study.
4. Number and percentage of adverse events of special interest (AESI) through the end of the study.
5. Number and percentage of medically attended adverse events (MAAE) through Day 28 and related MAAEs through the end of the study.
6. Grade 3 and 4 changes from baseline in safety laboratory parameters through the end of the study.
7. Neutralisation titre against Omicron XBB.1.16 variant measured as inhibitory concentration 50 (IC50) by PBNA and reported as reciprocal concentration for each individual sample and geometric mean titre (GMT) for treatment group comparison at Baseline and at Day 14.

Secondary endpoints 9

1. Neutralisation titre against Wuhan, Omicron BA.1 and Omicron XBB.1.5 variants measured as inhibitory concentration 50 (IC50) by PBNA and reported as reciprocal concentration for each individual sample and GMT for treatment group comparison at Baseline and at Days 14, 91 and 182.
2. Neutralisation titre against Omicron XBB.1.16 variant measured as inhibitory concentration 50 (IC50) by PBNA and reported as reciprocal concentration for each individual sample and GMT for treatment group comparison at Days 91 and 182.
3. Percentage of subjects experiencing an increase ≥4-fold in neutralizing antibody titres against Wuhan, Omicron BA.1, Omicron XBB.1.5 and Omicron XBB.1.16 variants measured as inhibitory concentration 50 (IC50) by PBNA for descriptive analysis, from Baseline to Day 14 in both vaccine arms.
4. Geometric mean fold rise (GMFR) in neutralising antibodies titres against Wuhan, Omicron BA.1, Omicron XBB.1.5 and Omicron XBB.1.16 variants for descriptive analysis, from Baseline to Day 14 in both vaccine arms.
5. Binding antibodies titre measured for each individual sample and GMT for treatment group comparison at Baseline and Days 14, 91 and 182.
6. Percentage of subjects experiencing an increase of ≥2-fold in total binding antibody titres against SARS-CoV-2 measured by ECLIA from Baseline to Day 14 for descriptive analysis in both vaccine arms.
7. Number of confirmed COVID-19 cases from ≥14 days after vaccination and through the end of the study for descriptive analysis in both vaccine arms.
8. Number of confirmed COVID-19 severe cases from ≥14 days after vaccination and through the end of the study for descriptive analysis in both vaccine arms.
9. T-cell-mediated response to the SARS-CoV-2 S glycoprotein as measured by whole PBMC stimulation by ELISpot at Baseline and at Day 14 for descriptive analysis in a subset of participants from both vaccine arms 2.

Investigational products

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

Test 1

Comparator 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

Hipra Scientific S.L.

Sponsor organisation

Hipra Scientific S.L.

Address

Avinguda Selva 135

City

Amer

Postcode

17170

Country

Spain

Locations

1 EU/EEA country · 10 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 2 files

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

Application history

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