Safety and Immunogenicity of Omicron Variant-Matched Vaccine Booster in Adults

NCT05383560 | Completed Phase 2 DMC

• 1 other identifier: Sheba-22-9312
• Study Type: interventional
• Target: 179
• Locations: 1 country
• Sites: 1

Brief Summary

Under protocol versions 1.01-1.06: The five recently emerged SARS-CoV2 variants that were designated as VOCs are the Alpha variant, Beta variant, Gamma variant, Delta variant and the Omicron variant. The current dominant Omicron variant was designated a VOC by WHO on Nov 26, 2021, and was found to comprise 85% of reported variants in late January 2022. Studies have shown that the prevalent Omicron mutations in the S1 subunit RBD region and NTD region could dramatically change the antigenic features of the viral spike, leading to significantly reduced neutralization Omicron harbors 30 signature mutations (\>50% prevalence) of which 15 are in the S1 subunit RBD region and 8 are in the S1 subunit NTD region. Omicron is a highly contagious variant with threatening immune evasion capabilities even despite robust immune response. Initial modeling showed the Omicron variant being 2.8 times more infectious than the Delta variant. While current vaccines are losing protection against Omicron with respect to infection and mild disease, there is still considerable protection from hospitalisation and severe COVID-19, especially after a booster dose. The International Coalition of Medicines Regulatory Authorities (ICMRA) COVID-19 Omicron Variant Workshop encouraged the international scientific community and vaccine developers to look at alternative approaches to monovalent vaccines. In ICMRA's view, companies should also explore the feasibility of developing bivalent or multivalent variant vaccines to determine if they offer advantages to monovalent vaccines. As advised by ICMRA, the investigated vaccine, mRNA-1273.214 is a bivalent vaccine containing the ancestral SARS-CoV-2 and the Omicron variant spike sequences that will be evaluated as a heterologous boost. Under protocol version 1.07:The study will also investigate the safety, reactogenicity and immune response of the mRNA-1273.222 administered as a boost vaccine after primary series vaccination comprising 3 doses of an mRNA vaccine . This study hypothesizes that the peak level of antibodies against SARS CoV-2, will be at two weeks after the first study dose is administered, which is similar to other recent findings (Anderson et al., 2022).2.2.1. The bivalent mRNA-1273.222 vaccine contains mRNA encoding for the spike protein of BA.4/BA.5 as well as mRNA encoding for the original (ancestral Wuhan-Hu-1) strain of the SARS-CoV-2 virus.

Conditions

COVID-19 Pandemic; Immunogenicity; SARS CoV 2 Infection; COVID-19

Keywords

mRNA1273.214; Omicron; Immunogenicity; COVID-19; Safety; mRNA1273.222

Outcome Measures

Primary Outcomes (3)

• Safety of the study vaccines after each dose

  Safety of the study vaccines will be measured by solicited and unsolicited adverse injection site reactions and systemic reactions from the time of each vaccination through 7 days post each vaccination/placebo administrations. AEs will be collected up to 29 days after injection. Unsolicited non-serious AEs, SAEs, NOCMCs, and MAAEs will be collected through 6 months after the first vaccine dose.

  6 Months

• Reactogenicity of the study vaccines after each dose

  Reactogenicity of the study vaccines will be measured by solicited and unsolicited adverse injection site reactions and systemic reactions from the time of each vaccination through 7 days post each vaccination/placebo administrations. AEs will be collected up to 29 days after injection. Unsolicited non-serious AEs, SAEs, NOCMCs, and MAAEs will be collected through 6 months after the first vaccine dose. The study will also assess reactogenicity using "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" Guide, via an electronic diary the participants would be required to complete every day for 7 consecutive days starting the day of each vaccine.

  6 Months

• Immune response to mRNA-1273.214, given as a fourth and fifth dose to participants who previously received mRNA primary series vaccination and one booster dose (third dose).

  Primary immunogenicity outcome will be measured by changes in geometric titers (GMTs) and geometric fold raise (GMFRs) of IgG and neutralizing antibodies (nAb), using a pseudovirus assay during all visits. Blood for immunogenicity will be collected at all visits (total of 6 visits).

  6 Months

Secondary Outcomes (2)

• Immunogenicity

  6 Months

• Investigational Product's Efficacy

  6 Months

Other Outcomes (5)

• Exploratory Immunogenicity

  6 Months

• Describe the immune response to mRNA-1273.214 and mRNA-1273.222 by assessment of Changes in Neutralizing Antibodies.

  Under protocol version 1.07: 6 Months

• Describe the immune response to mRNA-1273.214 and mRNA-1273.222 by Comparison of Neutralizing Antibodies against SARS-CoV-2 Wild Type and newly emerged variants

  Under protocol version 1.07: 6 Months

Study Arms (5)

mRNA-1273.214 + mRNA-1273.214

EXPERIMENTAL

Fourth \& Fifth doses of an investigational mRNA vaccine, 56 days apart N ≈ 60 Under protocol versions 1.01-1.06

Biological: mRNA-1273.214 Vaccine

mRNA-1273.214 + Placebo

EXPERIMENTAL

Fourth dose of an investigational mRNA vaccine followed by a fifth dose of placebo, 56 days apart N ≈ 60 Under protocol versions 1.01-1.06

Biological: mRNA-1273.214 Vaccine; Biological: Placebo

mRNA-1273 + Placebo

ACTIVE COMPARATOR

Fourth dose of the commercial mRNA vaccine, followed by a fifth dose of placebo, 56 days apart N ≈ 30 Under protocol versions 1.01-1.06

Biological: MRNA-1273 Vaccine; Biological: Placebo

mRNA-1273.214

EXPERIMENTAL

A booster dose of an investigational mRNA vaccine at Visit 1 (Day 1). N ≈ 30 Under protocol versions 1.07

Biological: mRNA-1273.214 Vaccine

mRNA-1273.222

ACTIVE COMPARATOR

A booster dose of the commercial mRNA vaccine at Visit 1 (Day 1). N ≈ 30 Under protocol versions 1.07

Biological: MRNA-1273.222 Vaccine

Interventions

mRNA-1273.214 Vaccine BIOLOGICAL

Omicron Variant-Matched Vaccine

mRNA-1273.214; mRNA-1273.214 + Placebo; mRNA-1273.214 + mRNA-1273.214

MRNA-1273 Vaccine BIOLOGICAL

Moderna's commercial COVID-19 Vaccine

Also known as: Spikevax

mRNA-1273 + Placebo

Placebo BIOLOGICAL

Normal Saline for injection

mRNA-1273 + Placebo; mRNA-1273.214 + Placebo

MRNA-1273.222 Vaccine BIOLOGICAL

Moderna's commercial COVID-19 Vaccine

Also known as: Spikevax Bivalent

mRNA-1273.222

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants 21 years of age, inclusively.
• Protocol versions 1.01-1.06:Individuals who previously received mRNA primary series vaccination AND a booster dose at least 4 months prior to Day 1. Documented confirmation of prior mRNA series vaccination receipt must be obtained prior to randomization. Protocol version 1.07:Individuals who had previously received mRNA primary series vaccination comprising at least 3 vaccine doses with the last one at least 6 months prior to Day 1. Documented confirmation of prior mRNA series vaccination receipt must be obtained prior to randomization. Note: subjects who had received 4 vaccine doses (i.e., a primary series of 3 doses and an additional boost) may also be enrolled under protocol version 1.07).
• Females and males of childbearing potential must be willing to use effective methods of contraception such as hormones (OCP, oral contraceptive pill), condom or occlusive cap with spermicidal agents, intrauterine device (IUD), or intrauterine system (IUS) as well as to refrain from donating sperm through 28 days following the last vaccination.
• Participant who is willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
• For Women of Child Bearing Potential (WOCBP): a negative pregnancy test on the day of vaccination (Visit 1 and Visit 4).
• Participant who is willing and able to operate an electronic diary.
• Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the six (6) weeks before enrollment, can be included.
• Capable of giving signed informed consent as described which includes understanding and compliance with the study procedures, requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Must agree not to enroll in another study of an investigational agent prior to completion of the study.

You may not qualify if:

• 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).
• Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19 or positive antigen test for SARS-CoV-2 at baseline.
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• Has known or suspected allergy or history of anaphylaxis, urticaria, or other significant AR to the vaccine or its excipients.
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• Inability to observe possible local reactions at the injection sites due to a physical condition or permanent body art.
• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Pregnant or breastfeeding women.
• Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), e.g., for cancer or an autoimmune disease, or planned receipt throughout the study. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study.
• Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention.

Sponsors & Collaborators

• Sheba Medical Center: lead
• ModernaTX, Inc.: collaborator

Study Sites (1)

Sheba Medical Center

Ramat Gan, 5265601, Israel

Location

Related Publications (1)

• Lustig Y, Barda N, Weiss-Ottolenghi Y, Indenbaum V, Margalit I, Asraf K, Doolman R, Chalkias S, Das R, Elfatarany G, Harats D, Kreiss Y, Regev-Yochay G. Humoral response superiority of the monovalent XBB.1.5 over the bivalent BA.1 and BA.5 mRNA COVID-19 vaccines. Vaccine. 2024 Sep 17;42(22):126010. doi: 10.1016/j.vaccine.2024.05.058. Epub 2024 May 27.

  PMID: 38806352 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

mRNA-1273.214 COVID-19 vaccine; 2019-nCoV Vaccine mRNA-1273

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

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Study Officials

• Gili Regev-Yochay, MD

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Pharmacy will be responsible for all IPs masking, using a masking sleeve on ready to use each injection.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Infection Prevention & Control Unit

Model Details: Protocol versions 1.01-1.06:Randomized, Observer-Blinded (2:2:1 ratio) Protocol version 1.07:Randomized, Observer-Blinded (1:1 ratio)

Study Record Dates

• First Submitted: May 15, 2022
• First Posted: May 20, 2022
• Study Start: September 5, 2022
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: February 21, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: will be available upon publication of results
• Access Criteria: Upon request. Requires collaborator's approval as well.

Locations

IL (1)