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

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

Detailed Description
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This is a Phase I, open-label, randomized, active-controlled study to assess the safety and immunogenicity of 2 dosages of AZD9838 compared with a licensed SARS-CoV-2 mRNA vaccine in approximately 90 healthy participants at least 18 years of age and less than 65 years of age. The duration of each participant's involvement in the study will be approximately 12 months following administration of study vaccination.

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

Conditions
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COVID-19, SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: AZD9838
* Biological: Licensed mRNA vaccine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Adults ≥ 18 to 64 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 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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: dosage 1 of AZD9838 18 to 64 years of age<br>Participants will receive 1 intramuscular dose of AZD9838. | Biological: AZD9838<br>* Intramuscular (IM) injection.<br>|
| Experimental: Arm 2: dosage 2 of AZD9838 18 to 64 years of age<br>Participants will receive 1 intramuscular dose of AZD9838. | Biological: AZD9838<br>* Intramuscular (IM) injection.<br>|
| Active Comparator: Arm 3: licensed mRNA vaccine 18 to 64 years of age<br>Participants will receive 1 intramuscular dose of the licensed mRNA vaccine. | Biological: Licensed mRNA vaccine<br>* Intramuscular (IM) injection.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, COVID-19, Coronavirus, SARS-CoV-2, mRNA vaccine