Clinical trial NCT06147063: A Randomized Trial Evaluating a mRNA-VLP Vaccine's Immunogenicity and Safety for COVID-19
Official title: A Phase I, Open-label, Randomized, Active-Controlled Study in Adults to Characterize the Safety and Immunogenicity of AZD9838 and AZD6563 Vaccine (ARTEMIS-C)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: COVID-19
SARS-CoV-2 Infection
Keywords: COVID-19
Coronavirus
Vaccine
SARS-CoV-2
mRNA vaccine
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-11-27
Enrollment: 243
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Incidence of immediate unsolicited adverse events (AE)
timeFrame: Within 30 minutes post vaccination
measure: Incidence of solicited adverse reactions (AR)
timeFrame: Through 7 days post vaccination.
measure: Incidence of unsolicited adverse events (AE)
timeFrame: Through 28 days post vaccination.
measure: Incidence of serious adverse events (SAE)
timeFrame: Through 12 months post vaccination
measure: Incidence of medically attended adverse events (MAAE)
timeFrame: Through 12 months post vaccination
measure: Incidence of adverse events of special interest (AESI)
timeFrame: Through 12 months post vaccination
measure: Geometric mean titer (GMT) for SARS-CoV-2 ancestral strain neutralizing antibodies
timeFrame: Day 29
measure: Geometric mean titer (GMT) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies
timeFrame: Day 29
measure: Geometric mean titer (GMT) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies
timeFrame: Day 29
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 ancestral strain neutralizing antibodies
timeFrame: Day 1 to Day 29
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies
timeFrame: Day 1 to Day 29
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies
timeFrame: Day 1 to Day 29
measure: Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 ancestral strain
timeFrame: Day 1 to Day 29
measure: Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron BA.4/5
timeFrame: Day 1 to Day 29
measure: Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron XBB.1.5
timeFrame: Day 1 to Day 29
Secondary outcomes:
measure: Geometric mean titer (GMT) for SARS-CoV-2 ancestral strain neutralizing antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean titer (GMT) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean titer (GMT) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 ancestral strain neutralizing antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies
timeFrame: Day 1 to Day 360
measure: Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 ancestral strain
timeFrame: Day 1 to Day 360
measure: Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron BA.4/5
timeFrame: Day 1 to Day 360
measure: Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron XBB.1.5
timeFrame: Day 1 to Day 360
measure: Geometric mean titer (GMT) for SARS-CoV-2 ancestral strain S protein binding antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean titer (GMT) for SARS-CoV-2 Beta variant S protein binding antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean titer (GMT) for SARS-CoV-2 Delta variant S protein binding antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean titer (GMT) for SARS-CoV-2 Omicron subvariant S protein binding antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 ancestral strain S protein binding antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 Beta variant S protein binding antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 Delta variant S protein binding antibodies
timeFrame: Day 1 to Day 360
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron subvariant S protein binding antibodies
timeFrame: Day 1 to Day 360
measure: Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 ancestral strain
timeFrame: Day 1 to Day 360
measure: Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Beta variant
timeFrame: Day 1 to Day 360
measure: Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Delta variant
timeFrame: Day 1 to Day 360
measure: Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Omicron subvariant
timeFrame: Day 1 to Day 360
measure: Geometric mean response of S-specific Th1 and Th2 by cytokine-producing T cells by phenotype
timeFrame: Day 1 to Day 180
measure: Incidence and titer of H. pylori and human anti-ferritin antibodies
timeFrame: Day 1 to Day 360
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Research Site
state: California
city: Rolling Hills Estates
country: United States
facility: Research Site
state: California
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: North Charleston
country: United States
facility: Research Site
state: South Carolina
Study officials:
References: