A Randomized Trial Evaluating a mRNA-VLP Vaccine's Immunogenicity and Safety for COVID-19

NCT06147063 | Completed Phase 1 FDA Drug

• 1 other identifier: D8670C00001
• Study Type: interventional
• Target: 243
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to characterize the safety and immunogenicity of AZD9838 and AZD6563 when administered as a single dose vaccination against SARS-CoV-2 in adults.

Conditions

COVID-19; SARS-CoV-2 Infection

Keywords

COVID-19; Coronavirus; Vaccine; SARS-CoV-2; mRNA vaccine

Outcome Measures

Primary Outcomes (13)

• Number of participants with immediate unsolicited adverse events (AE)

  Immediate unsolicited AEs were defined as having an onset within 30 minutes post vaccination.

  Within 30 minutes post vaccination

• Number of participants with injection site and systemic solicited adverse reactions (ARs)

  Injection site solicited ARs included injection site pain, injection site erythema (redness), and injection site swelling. Systemic solicited ARs included fever, chills, headache, myalgia (muscle aches and pains), and fatigue (physical or mental tiredness).

  Through 7 days post vaccination

• Number of participants with any unsolicited adverse events (AEs)

  Unsolicited AEs were any AEs reported in addition to predefined solicited ARs.

  Through 28 days post vaccination

• Number of participants with serious adverse events (SAEs), Medically-attended adverse events (MAAEs), and Adverse Events of Special Interest (AESIs)

  An SAE is an AE meeting one or more of: resulted in death; was immediately life-threatening; required or prolonged in-patient hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or was an important medical event that may have jeopardized the participant or required intervention to prevent the above. MAAEs are AEs leading to medically attended visits that were not routine physical examination or vaccination visits (eg, urgent care, emergency room, or unscheduled visits to/from medical personnel, including telemedicine). An AESI was an event of scientific and medical interest, specific to understanding the safety profile of the investigational vaccine, requiring close monitoring and rapid communication by Investigators to the Sponsor.

  Through 12 months post vaccination

• Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 ancestral strain neutralizing antibodies

  Model-adjusted GMTs and 95% CIs for SARS-CoV-2 ancestral strain neutralizing antibodies

  Day 29

• Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies

  Model-adjusted GMTs and 95% CIs for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies

  Day 29

• Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies

  Model-adjusted GMTs and 95% CIs for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies

  Day 29

• Geometric mean fold rise (GMFR) for SARS-CoV-2 ancestral strain neutralizing antibodies

  GMFR for SARS-CoV-2 ancestral strain neutralizing antibodies

  Day 1 to Day 29

• Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies

  GMFR for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies

  Day 1 to Day 29

• Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies

  GMFR for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies

  Day 1 to Day 29

• Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 ancestral strain

  Seroresponse was defined as GMFR \>=4 from baseline

  Day 1 to Day 29

• Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron BA.4/5

  Seroresponse was defined as GMFR \>=4 from baseline

  Day 1 to Day 29

• Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron XBB.1.5

  Seroresponse was defined as GMFR \>=4 from baseline

  Day 1 to Day 29

Secondary Outcomes (28)

• Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 ancestral strain neutralizing antibodies

  Day 1 to Day 360

• Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies

  Day 1 to Day 360

• Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies

  Day 1 to Day 360

• Geometric mean fold rise (GMFR) for SARS-CoV-2 ancestral strain neutralizing antibodies

  Day 1 to Day 360

• Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies

  Day 1 to Day 360

Study Arms (8)

AZ BA.4/5 5µg, 18-64 years

EXPERIMENTAL

Participants received a single intramuscular dose of AZD9838.

Biological: AZD9838

AZ BA.4/5 10µg, 18-64 years

EXPERIMENTAL

Participants received a single intramuscular dose of AZD9838.

Biological: AZD9838

Pfizer XBB.1.5, 18-64 years

ACTIVE COMPARATOR

Participants received a single intramuscular dose of the Pfizer XBB.1.5 vaccine.

Biological: Licensed SARS-CoV-2 mRNA vaccine

AZ XBB.1.5 5µg, 18-64 years

EXPERIMENTAL

Participants received a single intramuscular dose of AZD6563.

Biological: AZD6563

AZ XBB.1.5 10µg, 18-64 years

EXPERIMENTAL

Participants received a single intramuscular dose of AZD6563.

Biological: AZD6563

AZ XBB.1.5 5µg, >=65 years

EXPERIMENTAL

Participants received a single intramuscular dose of AZD6563.

Biological: AZD6563

AZ XBB.1.5 10µg, >=65 years

EXPERIMENTAL

Participants received a single intramuscular dose of AZD6563.

Biological: AZD6563

Pfizer XBB.1.5, >=65 years

ACTIVE COMPARATOR

Participants received a single intramuscular dose of the Pfizer XBB.1.5 vaccine.

Biological: Licensed SARS-CoV-2 mRNA vaccine

Interventions

AZD9838 BIOLOGICAL

Intramuscular (IM) injection.

AZ BA.4/5 10µg, 18-64 years; AZ BA.4/5 5µg, 18-64 years

AZD6563 BIOLOGICAL

Intramuscular (IM) injection.

AZ XBB.1.5 10µg, 18-64 years; AZ XBB.1.5 10µg, >=65 years; AZ XBB.1.5 5µg, 18-64 years; AZ XBB.1.5 5µg, >=65 years

Licensed SARS-CoV-2 mRNA vaccine BIOLOGICAL

Intramuscular (IM) injection.

Pfizer XBB.1.5, 18-64 years; Pfizer XBB.1.5, >=65 years

Eligibility Criteria

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

You may qualify if:

• Adults ≥ 18 years at the time of signing informed consent.
• Self-reported History of SARS-CoV-2 infection at least 6 months prior to study vaccination AND/OR prior completion of primary series vaccination against COVID-19, with the final dose received at least 6 months prior to study vaccination
• Negative SARS-CoV-2 RT-PCR test at Visit 1
• Body mass index (BMI) of \<35 kg/m2 at screening
• Medically stable - according to the judgement of the investigator, hospitalization within the study is not anticipated and participant is likely to remain in the study through the end of the protocol specified follow-up.

You may not qualify if:

• Acute illness/infection on day prior or day of dosing
• History of hypersensitivity to any component of the study vaccination, severe adverse reaction associated with a vaccine and/or severe allergic reaction
• Positive COVID-19 test result within 6 months of Visit 1
• Receipt of licensed, authorized, or investigational COVID-19 vaccines in the 6 months prior to administration of study intervention or expected receipt through completion of Visit 5.
• Receipt of any COVID-19 monoclonal antibody (licensed or investigational) within 3 months or receipt of immunoglobulin (non-COVID related) or blood products within 6 months prior to administration of study intervention, or expected receipt during the study
• Receipt of any licensed or investigational vaccine (other than licensed influenza vaccines or non-study COVID-19 vaccines) within 30 days prior to Visit 1 or expected receipt prior to completion of Visit 4. Licensed influenza vaccines are permitted beginning \> 14 days before and \> 14 days after administration of study intervention.
• Previous history of myocarditis or pericarditis
• Woman who are pregnant, lactating, or of child-bearing potential and not using a contraception or abstinence from at least 4 weeks prior to study vaccination and until at least 6 months after study vaccination
• Lab values above ULN (Serum creatinine, AST, ALT), below LLN (hemoglobin, WBC, Platelet count) or any lab value that in the opinion of the investigator is clinically significant or might confound analysis of the study results. Participants with laboratory values outside of the normal range may have the abnormal test repeated within the screening window and if the values are normal, then the participant can be randomized. If the repeated value remains outside of the normal range but it is not felt to be clinically significant by the Investigator, the case can be discussed with the AstraZeneca study physician and if they both agree the value is not clinically significant, the participant can be randomized
• History of malignancy within 5 years (treated non-melanoma skin cancer and locally treated cervical cancers allowed)
• Known or suspected congenital or acquired immunodeficiency
• Known or suspected autoimmune conditions as determined by history and /or physical examination
• Active infection with hepatitis B or C
• Troponin I levels above the normal range at the screening visit
• History of hypersensitivity to kanamycin or any aminoglycoside antibiotics (eg, neomycin, streptomycin, tobramycin, and gentamicin).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (5)

Research Site

Long Beach, California, 90815, United States

Location

Research Site

Rolling Hills Estates, California, 90274, United States

Location

Research Site

Chicago, Illinois, 60640, United States

Location

Research Site

Wichita, Kansas, 67207, United States

Location

Research Site

North Charleston, South Carolina, 29405, United States

Location

Related Links

• CSR Synopsis (redacted)

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: November 24, 2023
• First Posted: November 27, 2023
• Study Start: November 27, 2023
• Primary Completion: April 30, 2024
• Study Completion: March 27, 2025
• Last Updated: August 31, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (5)