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

A Phase I, Open-label, Randomized, Active-Controlled Study in Adults to Characterize the Safety and Immunogenicity of AZD9838 and AZD6563 Vaccine (ARTEMIS-C)

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2 Infection
• Intervention / Treatment: Biological: AZD9838; Biological: AZD6563; Biological: Licensed SARS-CoV-2 mRNA vaccine

Detailed Description

This is a Phase I, open-label, randomized, active-controlled study to assess the safety and immunogenicity of 2 dosages of AZD9838 and 2 dosages of AZD6563 compared with a licensed SARS-CoV-2 mRNA vaccine in approximately 240 healthy participants. AZD6563 will be assessed in adults 18 years of age and older. AZD9838 will be assessed in adults 18 to 64 years of age only.

The duration of each participant's involvement in the study will be approximately 12 months following administration of study vaccination.

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90815
      • Research Site
    • Rolling Hills Estates, California, United States, 90274
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Research Site
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Research Site
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZ BA.4/5 5µg, 18-64 years; Participants received a single intramuscular dose of AZD9838.	Biological: AZD9838; Intramuscular (IM) injection.
Experimental: AZ BA.4/5 10µg, 18-64 years; Participants received a single intramuscular dose of AZD9838.	Biological: AZD9838; Intramuscular (IM) injection.
Active Comparator: Pfizer XBB.1.5, 18-64 years; Participants received a single intramuscular dose of the Pfizer XBB.1.5 vaccine.	Biological: Licensed SARS-CoV-2 mRNA vaccine; Intramuscular (IM) injection.
Experimental: AZ XBB.1.5 5µg, 18-64 years; Participants received a single intramuscular dose of AZD6563.	Biological: AZD6563; Intramuscular (IM) injection.
Experimental: AZ XBB.1.5 10µg, 18-64 years; Participants received a single intramuscular dose of AZD6563.	Biological: AZD6563; Intramuscular (IM) injection.
Experimental: AZ XBB.1.5 5µg, >=65 years; Participants received a single intramuscular dose of AZD6563.	Biological: AZD6563; Intramuscular (IM) injection.
Experimental: AZ XBB.1.5 10µg, >=65 years; Participants received a single intramuscular dose of AZD6563.	Biological: AZD6563; Intramuscular (IM) injection.
Active Comparator: Pfizer XBB.1.5, >=65 years; Participants received a single intramuscular dose of the Pfizer XBB.1.5 vaccine.	Biological: Licensed SARS-CoV-2 mRNA vaccine; Intramuscular (IM) injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean fold rise (GMFR) for SARS-CoV-2 ancestral strain neutralizing antibodies	GMFR for SARS-CoV-2 ancestral strain neutralizing antibodies by visit.	Day 1 to Day 360
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 by visit.	Day 1 to Day 360
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 by visit.	Day 1 to Day 360
Geometric mean titer (GMT) for SARS-CoV-2 Omicron subvariant S protein binding antibodies	GMT for SARS-CoV-2 Omicron subvariant S protein binding antibodies by visit.	Day 1 to Day 360
Geometric mean fold rise (GMFR) for SARS-CoV-2 ancestral strain S protein binding antibodies	GMFR for SARS-CoV-2 ancestral strain S protein binding antibodies by visit.	Day 1 to Day 360
Geometric mean fold rise (GMFR) for SARS-CoV-2 Beta variant S protein binding antibodies	GMFR for SARS-CoV-2 Beta variant S protein binding antibodies by visit.	Day 1 to Day 360
Geometric mean fold rise (GMFR) for SARS-CoV-2 Delta variant S protein binding antibodies	GMFR for SARS-CoV-2 Delta variant S protein binding antibodies by visit.	Day 1 to Day 360
Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron subvariant S protein binding antibodies	GMFR for SARS-CoV-2 Omicron subvariant S protein binding antibodies by visit.	Day 1 to Day 360
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 by visit.	Day 1 to Day 360
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 by visit.	Day 1 to Day 360
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 by visit.	Day 1 to Day 360
Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 ancestral strain	Seroresponse was defined as GMFR >=4 from baseline by visit.	Day 1 to Day 360
Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron BA.4/5	Seroresponse was defined as GMFR >=4 from baseline by visit.	Day 1 to Day 360
Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron XBB.1.5	Seroresponse was defined as GMFR >=4 from baseline by visit.	Day 1 to Day 360
Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 ancestral strain S protein binding antibodies	Model-adjusted GMTs and 95% CIs for SARS-CoV-2 ancestral strain S protein binding antibodies by visit.	Day 1 to Day 360
Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Beta variant S protein binding antibodies	Model-adjusted GMTs and 95% CIs for SARS-CoV-2 Beta variant S protein binding antibodies by visit.	Day 1 to Day 360
Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Delta variant S protein binding antibodies	Model-adjusted GMTs and 95% CIs for SARS-CoV-2 Delta variant S protein binding antibodies by visit.	Day 1 to Day 360
Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 ancestral strain	Seroresponse was defined as GMFR >=4 from baseline by visit.	Day 1 to Day 360
Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Beta variant	Seroresponse was defined as GMFR >=4 from baseline by visit.	Day 1 to Day 360
Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Delta variant	Seroresponse was defined as GMFR >=4 from baseline by visit.	Day 1 to Day 360
Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Omicron subvariant	Seroresponse was defined as GMFR >=4 from baseline by visit.	Day 1 to Day 360
Geometric mean response of S-specific CD4+ T-cells expressing Th1 cytokines	Geometric mean response of S-specific T cells by phenotype as measured by an intracellular cytokine staining assay over time.	Day 1 to Day 180
Geometric mean response of S-specific CD4+ T-cells expressing Th2 cytokines	Geometric mean response of S-specific T cells by phenotype as measured by an intracellular cytokine staining assay over time.	Day 1 to Day 180
Geometric mean response of S-specific CD8+ T-cells expressing cytokines	Geometric mean response of S-specific T cells by phenotype as measured by an intracellular cytokine staining assay over time.	Day 1 to Day 180
Incidence of H. pylori anti-ferritin antibodies	Incidence of H. pylori anti-ferritin antibodies.	Day 1 to Day 360
Titer of H. pylori anti-ferritin antibodies	Titer of H. pylori anti-ferritin antibodies.	Day 1 to Day 360
Incidence of human anti-ferritin antibodies (light and/or heavy)	Incidence of human anti-ferritin antibodies (light and/or heavy).	Day 1 to Day 360
Titer of human anti-ferritin antibodies (light and/or heavy)	Incidence of human anti-ferritin antibodies (light and/or heavy).	Day 1 to Day 360

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• CSR Synopsis (redacted)

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): March 27, 2025

Study Registration Dates

• First Submitted: November 24, 2023
• First Submitted That Met QC Criteria: November 24, 2023
• First Posted (Actual): November 27, 2023

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: August 27, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Vaccine; Coronavirus; COVID-19; mRNA vaccine
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronaviridae Infections; Nidovirales Infections; COVID-19; Coronavirus Infections
• Other Study ID Numbers: D8670C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No