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

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 (Estimated): 240
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90815
      • Recruiting
      • Research Site
    • Rolling Hills Estates, California, United States, 90274
      • Recruiting
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Recruiting
      • Research Site
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Recruiting
      • Research Site
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Recruiting
      • 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: Arm 1: dosage 1 of AZD9838 18 to 64 years of age; Participants will receive 1 intramuscular dose of AZD9838.	Biological: AZD9838; Intramuscular (IM) injection.
Experimental: Arm 2: dosage 2 of AZD9838 18 to 64 years of age; Participants will receive 1 intramuscular dose of AZD9838.	Biological: AZD9838; Intramuscular (IM) injection.
Active Comparator: Arm 3: licensed mRNA vaccine 18 to 64 years of age; Participants will receive 1 intramuscular dose of the licensed mRNA vaccine.	Biological: Licensed mRNA vaccine; Intramuscular (IM) injection.
Experimental: Arm 4: dosage 1 of AZD6563 18 to 64 years of age; Participants will receive 1 intramuscular dose of AZD6563.	Biological: AZD6563; Intramuscular (IM) injection.
Experimental: Arm 5: dosage 2 of AZD6563 18 to 64 years of age; Participants will receive 1 intramuscular dose of AZD6563.	Biological: AZD6563; Intramuscular (IM) injection.
Experimental: Arm 6: dosage 1 of AZD6563 65 years of age and older; Participants will receive 1 intramuscular dose of AZD6563.	Biological: AZD6563; Intramuscular (IM) injection.
Experimental: Arm 7: dosage 2 of AZD6563 65 years of age and older; Participants will receive 1 intramuscular dose of AZD6563.	Biological: AZD6563; Intramuscular (IM) injection.
Active Comparator: Arm 8: licensed mRNA vaccine 65 years of age and older; Participants will receive 1 intramuscular dose of the licensed mRNA vaccine.	Biological: Licensed mRNA vaccine; Intramuscular (IM) injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of immediate unsolicited adverse events (AE)	Number of participants who experienced immediate unsolicited AEs within 30 minutes post vaccination.	Within 30 minutes post vaccination
Incidence of solicited adverse reactions (AR)	Number of participants who experienced injection site and systemic solicited ARs through 7 days post vaccination.	Through 7 days post vaccination.
Incidence of unsolicited adverse events (AE)	Number of participants who experienced unsolicited AEs through 28 days post vaccination.	Through 28 days post vaccination.
Incidence of serious adverse events (SAE)	Number of participants who experienced SAEs through 12 months post vaccination.	Through 12 months post vaccination
Incidence of medically attended adverse events (MAAE)	Number of participants who experienced MAAEs through 12 months post vaccination.	Through 12 months post vaccination
Incidence of adverse events of special interest (AESI)	Number of participants who experience AESIs through 12 months post vaccination.	Through 12 months post vaccination
Geometric mean titer (GMT) for SARS-CoV-2 ancestral strain neutralizing antibodies	GMT for SARS-CoV-2 ancestral strain neutralizing antibodies	Day 29
Geometric mean titer (GMT) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies	GMT for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies	Day 29
Geometric mean titer (GMT) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies	GMT 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	Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 ancestral strain, 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	Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron BA.4/5, 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	Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron XBB.1.5, defined as GMFR >=4 from baseline	Day 1 to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titer (GMT) for SARS-CoV-2 ancestral strain neutralizing antibodies	GMT for SARS-CoV-2 ancestral strain neutralizing antibodies by visit.	Day 1 to Day 360
Geometric mean titer (GMT) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies	GMT for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies by visit.	Day 1 to Day 360
Geometric mean titer (GMT) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies	GMT for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies by visit.	Day 1 to Day 360
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
Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 ancestral strain	Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 ancestral strain, 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	Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron BA.4/5, 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	Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron XBB.1.5, defined as GMFR >=4 from baseline by visit.	Day 1 to Day 360
Geometric mean titer (GMT) for SARS-CoV-2 ancestral strain S protein binding antibodies	GMT for SARS-CoV-2 ancestral strain S protein binding antibodies by visit.	Day 1 to Day 360
Geometric mean titer (GMT) for SARS-CoV-2 Beta variant S protein binding antibodies	GMT for SARS-CoV-2 Beta variant S protein binding antibodies by visit.	Day 1 to Day 360
Geometric mean titer (GMT) for SARS-CoV-2 Delta variant S protein binding antibodies	GMT for SARS-CoV-2 Delta variant S protein binding 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
Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 ancestral strain	Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 ancestral strain by visit.	Day 1 to Day 360
Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Beta variant	Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Beta variant by visit.	Day 1 to Day 360
Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Delta variant	Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Delta variant by visit.	Day 1 to Day 360
Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Omicron subvariant	Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Omicron subvariant by visit.	Day 1 to Day 360
Geometric mean response of S-specific Th1 and Th2 by cytokine-producing T cells by phenotype	Geometric mean response of S-specific Th1 and Th2 by cytokine-producing T cells by phenotype as measured by an intracellular cytokine staining assay over time.	Day 1 to Day 180
Incidence and titer of H. pylori and human anti-ferritin antibodies	Incidence and titer of H. pylori and human anti-ferritin antibodies over time.	Day 1 to Day 360

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Estimated): May 6, 2024
• Study Completion (Estimated): April 11, 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): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

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