COVID-19, SARS-CoV-2 Infection
Conditions
Keywords
COVID-19, Coronavirus, Vaccine, SARS-CoV-2, mRNA vaccine
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.
Interventions
BIOLOGICALAZD9838
Intramuscular (IM) injection.
BIOLOGICALLicensed SARS-CoV-2 mRNA vaccine
Intramuscular (IM) injection.
BIOLOGICALAZD6563
Intramuscular (IM) injection.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric mean fold rise (GMFR) for SARS-CoV-2 ancestral strain neutralizing antibodies | Day 1 to Day 29 | GMFR for SARS-CoV-2 ancestral strain neutralizing antibodies |
| Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies | Day 1 to Day 29 | GMFR for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies |
| Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies | Day 1 to Day 29 | GMFR for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies |
| Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 ancestral strain | Day 1 to Day 29 | Seroresponse was defined as GMFR \>=4 from baseline |
| Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron BA.4/5 | Day 1 to Day 29 | Seroresponse was defined as GMFR \>=4 from baseline |
| Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron XBB.1.5 | Day 1 to Day 29 | Seroresponse was defined as GMFR \>=4 from baseline |
| Number of participants with injection site and systemic solicited adverse reactions (ARs) | Through 7 days post vaccination | 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). |
| Number of participants with any unsolicited adverse events (AEs) | Through 28 days post vaccination | Unsolicited AEs were any AEs reported in addition to predefined solicited ARs. |
| Number of participants with immediate unsolicited adverse events (AE) | Within 30 minutes post vaccination | Immediate unsolicited AEs were defined as having an onset within 30 minutes post vaccination. |
| Number of participants with serious adverse events (SAEs), Medically-attended adverse events (MAAEs), and Adverse Events of Special Interest (AESIs) | Through 12 months post vaccination | 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. |
| Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 ancestral strain neutralizing antibodies | Day 29 | Model-adjusted GMTs and 95% CIs for SARS-CoV-2 ancestral strain neutralizing antibodies |
| Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies | Day 29 | Model-adjusted GMTs and 95% CIs for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies |
| Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies | Day 29 | Model-adjusted GMTs and 95% CIs for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies | Day 1 to Day 360 | GMFR for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies by visit. |
| Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 ancestral strain | Day 1 to Day 360 | Seroresponse was defined as GMFR \>=4 from baseline by visit. |
| Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron BA.4/5 | Day 1 to Day 360 | Seroresponse was defined as GMFR \>=4 from baseline by visit. |
| Proportion of participants with neutralizing antibody seroresponse against SARS-CoV-2 Omicron XBB.1.5 | Day 1 to Day 360 | Seroresponse was defined as GMFR \>=4 from baseline by visit. |
| Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 ancestral strain S protein binding antibodies | Day 1 to Day 360 | Model-adjusted GMTs and 95% CIs for SARS-CoV-2 ancestral strain S protein binding antibodies by visit. |
| Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Beta variant S protein binding antibodies | Day 1 to Day 360 | Model-adjusted GMTs and 95% CIs for SARS-CoV-2 Beta variant S protein binding antibodies by visit. |
| Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Delta variant S protein binding antibodies | Day 1 to Day 360 | Model-adjusted GMTs and 95% CIs for SARS-CoV-2 Delta variant S protein binding antibodies by visit. |
| Geometric mean titer (GMT) for SARS-CoV-2 Omicron subvariant S protein binding antibodies | Day 1 to Day 360 | GMT for SARS-CoV-2 Omicron subvariant S protein binding antibodies by visit. |
| Geometric mean fold rise (GMFR) for SARS-CoV-2 ancestral strain S protein binding antibodies | Day 1 to Day 360 | GMFR for SARS-CoV-2 ancestral strain S protein binding antibodies by visit. |
| Geometric mean fold rise (GMFR) for SARS-CoV-2 Beta variant S protein binding antibodies | Day 1 to Day 360 | GMFR for SARS-CoV-2 Beta variant S protein binding antibodies by visit. |
| Geometric mean fold rise (GMFR) for SARS-CoV-2 Delta variant S protein binding antibodies | Day 1 to Day 360 | GMFR for SARS-CoV-2 Delta variant S protein binding antibodies by visit. |
| Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron subvariant S protein binding antibodies | Day 1 to Day 360 | GMFR for SARS-CoV-2 Omicron subvariant S protein binding antibodies by visit. |
| Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 ancestral strain | Day 1 to Day 360 | Seroresponse was defined as GMFR \>=4 from baseline by visit. |
| Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Beta variant | Day 1 to Day 360 | Seroresponse was defined as GMFR \>=4 from baseline by visit. |
| Geometric mean response of S-specific CD4+ T-cells expressing Th2 cytokines | Day 1 to Day 180 | Geometric mean response of S-specific T cells by phenotype as measured by an intracellular cytokine staining assay over time. |
| Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Delta variant | Day 1 to Day 360 | Seroresponse was defined as GMFR \>=4 from baseline by visit. |
| Geometric mean response of S-specific CD8+ T-cells expressing cytokines | Day 1 to Day 180 | Geometric mean response of S-specific T cells by phenotype as measured by an intracellular cytokine staining assay over time. |
| Incidence of H. pylori anti-ferritin antibodies | Day 1 to Day 360 | Incidence of H. pylori anti-ferritin antibodies. |
| Titer of H. pylori anti-ferritin antibodies | Day 1 to Day 360 | Titer of H. pylori anti-ferritin antibodies. |
| Incidence of human anti-ferritin antibodies (light and/or heavy) | Day 1 to Day 360 | Incidence of human anti-ferritin antibodies (light and/or heavy). |
| Titer of human anti-ferritin antibodies (light and/or heavy) | Day 1 to Day 360 | Incidence of human anti-ferritin antibodies (light and/or heavy). |
| Geometric mean response of S-specific CD4+ T-cells expressing Th1 cytokines | Day 1 to Day 180 | Geometric mean response of S-specific T cells by phenotype as measured by an intracellular cytokine staining assay over time. |
| Proportion of participants with S protein binding antibody seroresponse against SARS-CoV-2 Omicron subvariant | Day 1 to Day 360 | Seroresponse was defined as GMFR \>=4 from baseline by visit. |
| Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 ancestral strain neutralizing antibodies | Day 1 to Day 360 | Model-adjusted GMTs and 95% CIs for SARS-CoV-2 ancestral strain neutralizing antibodies by visit. |
| Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies | Day 1 to Day 360 | Model-adjusted GMTs and 95% CIs for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies by visit. |
| Model-adjusted geometric mean titer (GMT) for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies | Day 1 to Day 360 | Model-adjusted GMTs and 95% CIs for SARS-CoV-2 Omicron XBB.1.5 neutralizing antibodies by visit. |
| Geometric mean fold rise (GMFR) for SARS-CoV-2 ancestral strain neutralizing antibodies | Day 1 to Day 360 | GMFR for SARS-CoV-2 ancestral strain neutralizing antibodies by visit. |
| Geometric mean fold rise (GMFR) for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies | Day 1 to Day 360 | GMFR for SARS-CoV-2 Omicron BA.4/5 neutralizing antibodies by visit. |
Countries
United States
Outcome results
None listed