Safety and Tolerability of COVID-19 Vaccine (ABNCoV2)

NCT04839146 | Completed Phase 1 Results

• 1 other identifier: NL76192.000.20
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1 trial aims to assess the safety and tolerability of two doses of ABNCoV2, formulated with and without the adjuvant MF59, in healthy adult volunteers and to identify the dosage and formulation that optimizes the immunogenicity-tolerability ratio 14 days following first vaccination with ABNCoV2.

Conditions

Covid19; Severe Acute Respiratory Syndrome; SARS-CoV-2 Infection

Outcome Measures

Primary Outcomes (2)

• Number of at Least Possibly Related Grade 3 Adverse Events (AE) and Serious Adverse Events (SAE)

  Primary safety endpoint: Number of at least possibly related Grade 3 adverse events (AE) and serious adverse events (SAE)

  up to 28 weeks

• Concentration of ABNCoV2-specific Antibodies 14 Days Following First Vaccination

  Primary immunogenicity endpoint: Concentration of ABNCoV2-specific antibodies 14 days following first vaccination

  14 days following first vaccination.

Secondary Outcomes (1)

• Number of Participants With at Least Possibly Related Solicited AEs

  one week after each vaccination with of ABNCoV2.

Other Outcomes (4)

• Concentration of ABNCoV2-specific Antibodies at Baseline and During Immunization and Follow up.

  up to 28 weeks

• Inhibitory Titre in Invasion Inhibition Assay at Baseline and During Immunization and Follow up.

  up to 28 weeks

• Cellular Immune Responses (T and B Cell) at Baseline and During Immunization and Follow up.

  up to 28 weeks

Study Arms (7)

Group 1: 6 microgram ABNCoV2 with/without MF59 adjuvant

EXPERIMENTAL

In Group 1 (n=6), subjects will receive 6 μg ABNCoV2 intramuscularly, half of whom (n=3) will receive the non-adjuvanted vaccine formulation and the other half (n=3) will receive the MF59-adjuvanted vaccine formulation. All subjects will receive a second vaccination with the same dose and formulation 4 weeks following the first vaccination.

Biological: ABNCoV2 Vaccine

Group 2: 12 microgram ABNCoV2 with/without MF59 adjuvant

EXPERIMENTAL

In Group 2 (n=6), subjects will receive 12 μg ABNCoV2 intramuscularly, half of whom (n=3) will receive the non-adjuvanted vaccine formulation and the other half (n=3) will receive the MF59-adjuvanted vaccine formulation. All subjects will receive a second vaccination with the same dose and formulation 4 weeks following the first vaccination.

Biological: ABNCoV2 Vaccine

Group 3: 25 microgram ABNCoV2 with/without MF59 adjuvant

EXPERIMENTAL

In Group 3 (n=6), subjects will receive 25 μg ABNCoV2 intramuscularly, half of whom (n=3) will receive the non-adjuvanted vaccine formulation and the other half (n=3) will receive the MF59-adjuvanted vaccine formulation. All subjects will receive a second vaccination with the same dose and formulation 4 weeks following the first vaccination.

Biological: ABNCoV2 Vaccine

Group 4: 50 microgram ABNCoV2 with/without MF59 adjuvant

EXPERIMENTAL

In Group 4 (n=6), subjects will receive 50 μg non-adjuvanted or MF59-adjuvanted ABNCoV2 intramuscularly. All subjects will receive a second vaccination with the same dose and formulation 4 weeks following the first vaccination.

Biological: ABNCoV2 Vaccine

Group 5: 70 microgram ABNCoV2 with/without MF59 adjuvant

EXPERIMENTAL

In Group 5 (n=6), subjects will receive 70 μg non-adjuvanted or MF59-adjuvanted ABNCoV2 intramuscularly. All subjects will receive a second vaccination with the same dose and formulation 4 weeks following the first vaccination.

Biological: ABNCoV2 Vaccine

Group 6: t.b.d. microgram ABNCoV2 with/without MF59 adjuvant

EXPERIMENTAL

The subjects in Group 6 (n=6) will receive the next lower dosage of the highest non-adjuvanted or MF59-adjuvanted ABNCoV2 dose achieved intramuscularly. All subjects will receive a second vaccination with the same dose and formulation 4 weeks following the first vaccination.

Biological: ABNCoV2 Vaccine

Group 7: t.b.d. microgram ABNCoV2 with/without MF59 adjuvant

EXPERIMENTAL

The subjects in Group 7 (n=6) will receive the highest non-adjuvanted or MF59-adjuvanted ABNCoV2 dose achieved intramuscularly. All subjects will receive a second vaccination with the same dose and formulation 4 weeks following the first vaccination.

Biological: ABNCoV2 Vaccine

Interventions

ABNCoV2 Vaccine BIOLOGICAL

SARS-CoV-2 vaccine

Also known as: cVLP-RBD, RBDn-CLP, ABNCoV2

Group 1: 6 microgram ABNCoV2 with/without MF59 adjuvant; Group 2: 12 microgram ABNCoV2 with/without MF59 adjuvant; Group 3: 25 microgram ABNCoV2 with/without MF59 adjuvant; Group 4: 50 microgram ABNCoV2 with/without MF59 adjuvant; Group 5: 70 microgram ABNCoV2 with/without MF59 adjuvant; Group 6: t.b.d. microgram ABNCoV2 with/without MF59 adjuvant; Group 7: t.b.d. microgram ABNCoV2 with/without MF59 adjuvant

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must sign written informed consent to participate in the trial.
• Subject is able to understand planned study procedures and demonstrate comprehension of the protocol procedures and knowledge of the study by passing a quiz (assessment of understanding). Subjects must score at least 80% correct on a multiple-choice quiz. If they do not score 80% on the initial quiz, the protocol information will be reviewed with them, and they will have the opportunity to retest.
• In the opinion of the investigator, the subject can and will comply with the requirements of the protocol.
• Subjects are available to attend all study visits and are reachable by phone throughout the entire study period from day -1 until 24 weeks following last vaccination (end of study).
• Subject is a male or non-pregnant and non-lactating female age ≥ 18 and ≤ 55 years and in good health at time of ABNCoV2 administration.
• Subject agrees to their general practitioner (GP) being informed about participation in the study and agrees to sign a form to request the release by their GP, and medical specialist when necessary, of any relevant medical information concerning possible contra-indications for participation in the study to the investigator(s).
• The subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period according to current Sanquin guidelines.

You may not qualify if:

• Any clinically significant abnormal finding on clinical examination or laboratory screening tests according to the US Food and Drug Administration (FDA) Toxicity Grading Scale for Healthy Adult and Adolescent Subjects Enrolled in Preventative Vaccine Clinical Trials \[30\].
• \. History of COVID-19 infection. 3. Chronic use of immunosuppressive drugs or other immune modifying drugs within six months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period.
• \. Screening tests positive for SARS-CoV-2, SARS-CoV-2 antibodies, Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV).
• \. Receipt of any investigational or non-registered product (drug or vaccine) other than the study product in the 30 days preceding enrolment or during the study period.
• \. Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
• \. Immunization with any vaccines within the past four weeks or planned receipt of a vaccine during the study period with the exception of a licensed SARS-CoV-2 vaccine, given within the framework of the national SARS-CoV-2 vaccination campaign. The time between last vaccination with ABNCoV2 and a SARS-CoV-2 vaccine provided by the campaign shall be at least 4 weeks.
• \. Known hypersensitivity to any of the vaccine components (adjuvant or protein).
• \. Administration of immunoglobulins and/or any blood products within the three months prior to the first dose of ABNCoV2 or planned administration during the study period.
• \. Previous participation in a COVID-19 vaccine study. 12. Body Mass Index (BMI) \>35 kg/m2. 13. Pregnancy, lactation or intention to become pregnant during the study period.
• \. History of drug or alcohol abuse interfering with normal functioning in the five years preceding enrolment.
• \. Being an employee or student of the department of Medical Microbiology of the Radboudumc, or a person otherwise related to the investigator other than a professional relationship for clinical trial purpose only.
• \. Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Sponsors & Collaborators

• European Union: collaborator
• Radboud University Medical Center: lead

Study Sites (1)

Radboud univserity medical center

Nijmegen, Gelderland, 6525GA, Netherlands

Location

Related Publications (1)

• Smit MJ, Sander AF, Ariaans MBPA, Fougeroux C, Heinzel C, Fendel R, Esen M, Kremsner PG, Ter Heine R, Wertheim HF, Idorn M, Paludan SR, Underwood AP, Binderup A, Ramirez S, Bukh J, Soegaard M, Erdogan SM, Gustavsson T, Clemmensen S, Theander TG, Salanti A, Hamborg M, de Jongh WA, McCall MBB, Nielsen MA, Mordmuller BG; COUGH-1 trial study group. First-in-human use of a modular capsid virus-like vaccine platform: an open-label, non-randomised, phase 1 clinical trial of the SARS-CoV-2 vaccine ABNCoV2. Lancet Microbe. 2023 Mar;4(3):e140-e148. doi: 10.1016/S2666-5247(22)00337-8. Epub 2023 Jan 18.

  PMID: 36681093 RESULT

MeSH Terms

Conditions

COVID-19; Severe Acute Respiratory Syndrome

Interventions

ABNCoV2 vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Benjamin Mordmüller (Principal investigator)
• Organization: Radboudumc

benjamin.mordmueller@radboudumc.nl

+31 (0)24 3619499

Study Officials

• Benjamin Mordmüller, Prof

  Stichting Radboud university medical center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: ABNCoV2 is a virus-like particle vaccine. It will be administered as two intramuscular injections in groups of up to 9 volunteers. All subjects will receive a second vaccination with the same dose and formulation 4 weeks following the first vaccination. The pre-defined escalation schedule will start with 6 μg ABNCoV2, followed by 12, 25 and 50 μg with a maximum dose of 70 μg. MF59-adjuvanted and non-adjuvanted formulations will be tested in parallel to detect superiority or futility of the MF59-adjuvanted against the non-adjuvanted formulation at the 6, 12 and 25 μg dosage. Approval for further dose escalation and choice of adjuvant use will be provided by a safety monitoring committee (SMC), supported by pre-defined analyses of safety, tolerability and immunogenicity data at day 14 post-first-vaccination. Recruitment for the two best (safe, tolerable and most immunogenic) regimens will continue until 12 volunteers per regimen have been immunized.

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: April 9, 2021
• Study Start: March 11, 2021
• Primary Completion: December 30, 2021
• Study Completion: February 25, 2022
• Last Updated: February 17, 2026
• Results First Posted: February 12, 2024

Record last verified: 2022-03

Locations

NL (1)