COVID-19 Vaccines
Conditions
Keywords
ARCT-154, COVID-19, SARS-CoV-2, Immunogenicity, Efficacy
Brief summary
This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind study designed to evaluate the safety, immunogenicity and efficacy of ARCT-154 in adult participants to be enrolled in Vietnam. This study consists of four parts: Part 1 (Phase 1) will evaluate the safety of the study vaccines in 100 healthy individuals. Part 2 (Phase 2) will evaluate the safety and immunogenicity of the study vaccines in 300 healthy individuals. Part 3 (Phase 3a) will evaluate the safety, immunogenicity, and efficacy of the study vaccines in 600 individuals with and without underlying medical conditions. Part 4 (Phase 3b) will evaluate the safety and efficacy of the study vaccines in 16,000 individuals with and without underlying medical conditions. Part 5 (Phase 3c) will evaluate the safety and non-inferiority in immunogenicity of ARCT-154 vaccine vs. Astra Zeneca COVID-19 vaccine (ChAdOx1 nCoV-19) in 2400 individuals with and without underlying medical conditions. In Phase 1, healthy individuals 18 to \< 60 years of age will be enrolled. In Phase 2, 3a, and 3b, individuals 18 years of age and older will be enrolled including individuals with underlying medical conditions that put them at higher risk of complications of COVID-19 disease. Phase 1, Phase 2, Phase 3a and Phase 3b participants will be randomly assigned to a study group that will receive up to 2 vaccination series. Each vaccination series comprises two vaccinations at 28-day intervals: an initial vaccination series with vaccinations on Day 1 and Day 29 and an additional vaccination series around 2 months after the first series (on Day 92 and 120). Participants of Phase 2, 3a who received 2 doses of ARCT-154 vaccine will be rerandomized to receive either dose 3 of ARCT-154 on Day 92 plus placebo on Day 120 or placebo on Day 92 plus placebo on Day 120. For Phase 1, Phase 3b and participants in Phase 2 and 3a that received placebo in the first vaccination series, the participants will be switched over to the opposite vaccine in the second series. There is no second vaccination series for Phase 3c as all participants receive active vaccine in the initial series.
Detailed description
Phase 1 will enroll 100 healthy participants that are randomly assigned 3:1 to receive ARCT-154 or placebo (75:25) for the initial series of vaccinations. In Phase 2, 300 participants will be randomly assigned 3:1 to receive ARCT-154 or placebo for the initial series of vaccinations. Participants that received ARCT-154 in the initial series will be rerandomized 3:1 to receive ARCT or placebo on Day 92 followed by placebo on Day 120. In Phase 3a, 600 participants will be randomly assigned 3:1 to receive ARCT-154 or placebo for the initial series of vaccinations. Participants that received ARCT-154 in the initial series will be rerandomized 3:1 to receive ARCT or placebo on Day 92 followed by placebo on Day 120. In Phase 3b, \ 16,000 participants will be randomly assigned 1:1 to receive ARCT-154 or placebo for the initial series of vaccinations. In Phase 3c, \ 2,400 participants will be randomly assigned 1:1 to receive ARCT-154 or Astra Zeneca COVID-19 vaccine. Blood samples will be collected and reserved for Immunogenicity evaluation for the first 1500 participants (3c-1) and assays for immunogenicity evaluation will be performed for the first 800 participants. Phase 1 participants must be \<60 years of age and healthy. Phase 2, 3a, and 3b and 3c participants will include elderly (≥60 years) and those with comorbidities. For Phase 2, 3a, 3b and 3c, prior to randomization, participants will be stratified by age (\< 60 or ≥ 60 years of age) and for participants \< 60 years of age by risk of severe COVID 19. Participants will be followed up for approximately 1 year after completion of the initial vaccination series. An independent Data and Safety Monitoring Board (DSMB) will perform ongoing review of blinded and unblinded data. An independent blinded adjudication committee will adjudicate all suspected COVID-19 cases to determine if they meet the primary endpoint requirements.
Interventions
BIOLOGICALARCT-154 Self-Amplifying RNA SARS-CoV-2 Vaccine
ARCT-154 Self-Amplifying RNA SARS-CoV-2 Vaccine
OTHERPlacebo (normal saline)
Normal saline with the same volume as of ARCT-154
BIOLOGICALAstra Zeneca COVID-19 vaccine
Astra Zeneca COVID-19 vaccine (ChAdOx1 nCoV-19)
Sponsors
Arcturus Therapeutics, Inc.
Vinbiocare Biotechnology Joint Stock Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Observer-blind design: Investigators, site staff, participants, CRO staff, Sponsor representatives with oversight of study conduct or study-related assessments will remain blinded to vaccine assignments for the study duration.
Intervention model description
Phase 1, 2, 3a, 3b: Participants will be randomly assigned to a study group that will receive up to 2 vaccination series. Each vaccination series comprises two vaccinations at 28-day intervals: an initial vaccination series with vaccinations on Day 1 and Day 29 and an additional vaccination series at around 2 months after the first series on Day 92 and 120. Each participant is planned to receive a two-dose vaccination series of ARCT-154 at a dose of 5 µg or a two-dose vaccination series of placebo (saline) in the first series. Participants in Phase 2, 3a who received 2 doses of ARCT-154 vaccine in the first vaccine series will be rerandomized to receive either dose 3 of ARCT-154 on Day 92 plus placebo on Day 120 or placebo on Day 92 plus placebo on Day 120. Phase 3c: Participants will be randomly assigned to a study group to receive two-dose vaccination series of ARCT-154 at a dose of 5 µg or approved COVID-19 vaccine comparator (Astra Zeneca's COVID-19 vaccine).
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
Individuals who: 1. are able to provide consent 2. agree to comply with all study visits and procedures 3. are of childbearing potential and sexually active must be willing to adhere to contraceptive requirements 4. are male or female ≥18 years of age (or, for Phase 1, 18 to \< 60 years of age) 5. are at higher risk of developing COVID-19 based on where they work or live
Exclusion criteria
Individuals who: 1. Significant infection or other acute illness, including body temperature \>100.4°F (\>38.0°C) on the day prior to or Day 1. Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator. 2. Pregnant or breastfeeding. 3. Known history of COVID-19 (asymptomatic SARS-CoV-2 infection and/or nucleocapsid positive test is not exclusionary). 4. Close contact with a person known to be SARS-CoV-2 positive or with a clinical diagnosis of COVID-19 within 7 days prior to enrollment. Participants meeting this criterion who remain asymptomatic for 7 days may be rescheduled for enrollment within the relevant windows. 5. Known history of anaphylaxis, urticaria, or other significant adverse reaction to the vaccine or its excipients. 6. Known history of anaphylaxis to other vaccines. 7. Bleeding disorder considered a contraindication to intramuscular (IM) injection or phlebotomy. 8. Immunosuppressive or immunodeficient state, asplenia, recurrent severe infections, or known to be HIV positive. 9. An underlying clinically significant acute or chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. Prior/Concomitant Therapy 10. Has previously received investigational or approved MERS-CoV, SARS-CoV, SARS-CoV-2 vaccines or who have plans to receive off-study COVID-19 vaccines. 11. Has received a live replicating vaccine within 28 days prior to each study vaccination or a licensed inactivated or non-replicating vaccine within 14 days prior to first study vaccination. 12. Has received treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, within 6 months prior to Screening, or planned receipt throughout the study. If systemic corticosteroids have been administered short term (\<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days prior to first study vaccine administration. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted. 13. Has received systemic immunoglobulins or blood products within 3 months prior to first study vaccine administration or plans to receive such products during the study. Other Exclusions 14. Demonstrated inability to comply with the study procedures. 15. Investigator site staff members, employees of the Sponsor or the CRO directly involved in the conduct of the study, or site staff members otherwise supervised by the investigator, or immediate family members of any of the previously mentioned individuals. 16. Other restrictions apply to Phase 1 participants to ensure they are healthy. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Solicited Local Adverse Reactions (ARs) | Within 7 days after Dose 1 and Dose 2 (up to Day 7 and 36) | Solicited local ARs included injection site erythema, injection site pain, injection site induration/swelling, and injection site tenderness. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants Reporting Solicited Systemic ARs | Within 7 days after Dose 1 and Dose 2 (up to Day 7 and 36) | Solicited systemic ARs included arthralgia, chills, diarrhea, dizziness, fatigue, fever (categorized by measured body temperature), headache, myalgia, and nausea/vomiting. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants Reporting Unsolicited Adverse Events (AEs) | Approximately 28 days after Dose 1 and Dose 2 (Day 1 to Day 29 and Day 29 to Day 57) | Unsolicited AEs were defined as any spontaneously reported or discovered AE. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | Day 1 to Day 92 | An MAAE was defined as an AE that led to an unscheduled visit (including a telemedicine visit) with a healthcare provider (\[HCP\], e.g., nurse, nurse practitioner, physician's assistant, physician). An SAE was defined as any event that resulted in death, was immediately life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect arising from a pregnancy conceived after receipt of study vaccine. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants With Neutralizing Antibody (NAb) Responses | Day 57 | Data are presented for the number of participants with a NAb seroconversion response as determined by the surrogate virus neutralization test (sVNT). Seroconversion was defined as a ≥4-fold increase in antibody concentration from baseline. |
| Number of Participants With a First Occurrence of Coronavirus Disease 2019 (COVID-19) | Day 36 to Day 92 | COVID-19 was defined as a positive SARS-CoV-2 test and at least one of the following that was a new or worsening finding: ⦁ Fever or chills ⦁ Cough ⦁ Shortness of breath or difficulty breathing ⦁ Fatigue ⦁ Muscle or body aches ⦁ Headache ⦁ New loss of taste or smell ⦁ Sore throat ⦁ Congestion or runny nose ⦁ Nausea or vomiting ⦁ Diarrhea Data are presented for the number of participants with a first occurrence of COVID-19 with no evidence of prior infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Seroconverting on Neutralizing Antibody Responses by Plaque Reduction Neutralization Test at 50% Reduction (PRNT50) | Days 29 and 57 | The plaque reduction neutralization test (PRNT) is a live virus assay. Neutralizing antibody titers were calculated as the highest serum dilution that resulted in 50% reduction in the number of virus plaques (PRNT50). Data presented is for the ancestral-clinical isolate variant. Data are presented for the number of participants that demonstrated seroconversion (as defined by 4-fold increase in neutralizing antibody concentration from baseline) on PRNT50. |
| Number of Participants With a First Occurrence of Severe COVID-19 | Day 36 to Day 92 | Number of participants with a first occurrence of severe COVID-19 in participants with no evidence of prior infection. Severe COVID-19 was defined as a positive SARS-CoV-2 test, symptoms per protocol-defined COVID-19 and any of the following: Clinical signs at rest indicative of severe systemic illness: - Respiratory rate ≥30 per minute, - Heart rate ≥125 per minute, - Oxygen saturation (SpO2) ≤93% on room air at sea level or partial pressure of oxygen (PO2)/fraction of inspired oxygen (FiO2) \<300 millimeter of mercury (mm Hg) - Respiratory failure (defined as needing high flow oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation \[ECMO\]); Evidence of shock: - Systolic blood pressure (SBP) \<90 mm Hg, or - Diastolic blood pressure (DBP) \<60 mm Hg, or requiring vasopressors, - Significant acute renal, hepatic, or neurologic dysfunction - Admission to an intensive care unit (ICU) - Death |
| Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies | Days 1, 29, 57 and 92 | — |
| Number of Participants With a First Occurrence of COVID-19 Irrespective of Prior Infection | Day 36 to Day 92 | Number of participants with a first occurrence of COVID-19 irrespective of prior infection. |
| Number of Participants With a First Occurrence of COVID-19 | Day 1 to Day 92 | Number of participants with a first occurrence of COVID-19 in participants with no evidence of prior infection. |
| Number of Participants With Death Due to COVID-19 | Day 36 to Day 92 | Number of participants with death due to COVID-19 in participants with no evidence of prior infection. |
| Geometric Mean Fold Rise in SARS-CoV-2 Neutralizing Antibody Titers | Days 29, 57, 92 | — |
| Number of Participants Seroconverting for Neutralizing Antibodies | Days 29, 57 and 92 | Seroconversion was defined as a ≥4-fold increase in antibody concentration from baseline as measured by the sVNT test. Data are presented for the number of participants seroconverting for neutralizing antibodies. |
| Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies | Days 1, 29, 57, 92 | — |
| Geometric Mean Fold Ratio of Spike Protein IgG Binding Antibodies | Days 29, 57, 92 | — |
| Number of Participants Seroconverting for Spike Protein IgG Binding Antibodies | Days 29, 57, 92 | Seroconversion was defined as a ≥4-fold increase in antibody concentration from baseline. Data are presented for the number of participants seroconverting for spike protein IgG binding antibodies. |
Countries
Vietnam
Participant flow
Pre-assignment details
As pre-specified, data were collected and are reported per vaccine group overall for all study phases combined. Data are reported per first treatment received.
Participants by arm
| Arm | Count |
|---|---|
| ARCT-154 This study was conducted in 3 phases (Phase 1, 2, 3a, 3b, 3c). Phase 1, 2, 3a, 3b: Participants were randomly assigned to receive up to 2 vaccination series at 28-day intervals: an initial vaccination series with vaccinations on Day 1 and Day 29 and an additional vaccination series on Day 92 and 120. Each participant received a two-dose vaccination series of ARCT-154 at a dose of 5 µg or a two-dose vaccination series of placebo (saline) in the first series. In the second vaccination series, participants in Phase 1 and 3b received a two-dose vaccination series with the opposite vaccine on Day 92 and 120 (Switchover vaccination series). Participants in Phase 2 and 3a who received 2 doses of ARCT-154 vaccine in the first vaccine series were re-randomized to receive either dose 3 of ARCT-154 on Day 92 plus placebo on Day 120 or placebo on Day 92 plus placebo on Day 120. Phase 3c: Participants were randomly assigned to a study group to receive two-dose vaccination series (Day 1 and Day 29) of ARCT-154 at a dose of 5 µg or approved COVID-19 vaccine comparator (Astra Zeneca's COVID-19 vaccine \[ChAdOx1 nCoV-19\]). In Phase 3c, participants received only 2 doses of their assigned treatment (no switchover) on Days 1 and 29. As pre-specified, data are presented pooled per treatment received. Data in this arm are presented pooled for ARCT-154 received in Phases 1, 2, 3a, 3b. | 8,807 |
| Placebo This study was conducted in 3 phases (Phase 1, 2, 3a, 3b, 3c). Phase 1, 2, 3a, 3b: Participants were randomly assigned to receive up to 2 vaccination series at 28-day intervals: an initial vaccination series with vaccinations on Day 1 and Day 29 and an additional vaccination series on Day 92 and 120. Each participant received a two-dose vaccination series of ARCT-154 at a dose of 5 micrograms (µg) or a two-dose vaccination series of placebo (saline) in the first series. In the second vaccination series, participants in Phase 1 and 3b received a two-dose vaccination series with the opposite vaccine on Day 92 and 120 (Switchover vaccination series). Participants in Phase 2 and 3a who received 2 doses of ARCT-154 vaccine in the first vaccine series were re-randomized to receive either dose 3 of ARCT-154 on Day 92 plus placebo on Day 120 or placebo on Day 92 plus placebo on Day 120. Phase 3c: Participants were randomly assigned to a study group to receive two-dose vaccination series of ARCT-154 at a dose of 5 µg or approved COVID-19 vaccine comparator (Astra Zeneca's COVID-19 vaccine \[ChAdOx1 nCoV-19). In Phase 3c, participants received only 2 doses of their assigned treatment (no switchover) on Days 1 and 29. As pre-specified, data are presented pooled per treatment received. Data in this arm are presented pooled for placebo received in Phases 1, 2, 3a, 3b. | 8,294 |
| Phase 3c: ARCT-154 Phase 3c: Participants were randomly assigned to a study group to receive ARCT-154 at a dose of 5 µg on Day 1 and Day 29. In Phase 3c, participants received only 2 doses of their assigned treatment (no switchover). Data in this arm are presented pooled for ARCT-154 vaccine received in Phase 3c. | 1,186 |
| Astra Zeneca COVID-19 vaccine Phase 3c: Participants were randomly assigned to a study group to receive ARCT-154 at a dose of 5 µg or approved COVID-19 vaccine comparator (Astra Zeneca's COVID-19 vaccine \[ChAdOx1 nCoV-19\]) on Day 1 and Day 29. In Phase 3c, participants received only 2 doses of their assigned treatment (no switchover) on Days 1 and 29. As pre-specified, data are presented pooled per treatment received. Data in this arm are presented pooled for Astra Zeneca COVID-19 vaccine received in Phase 3c. | 1,180 |
| Total | 19,467 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 0 |
| Overall Study | Death | 25 | 17 | 4 |
| Overall Study | Lost to Follow-up | 11 | 24 | 3 |
| Overall Study | Other than Specified | 2 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1,052 | 1,006 | 20 |
Baseline characteristics
| Characteristic | ARCT-154 | Placebo | Phase 3c: ARCT-154 | Astra Zeneca COVID-19 vaccine | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.0 Years | 48.0 Years | 52.0 Years | 52.0 Years | 48.0 Years |
| Race/Ethnicity, Customized Other | 50 Participants | 55 Participants | 1 Participants | 3 Participants | 109 Participants |
| Race/Ethnicity, Customized The Kinh | 8757 Participants | 8239 Participants | 1185 Participants | 1177 Participants | 19358 Participants |
| Sex: Female, Male Female | 4441 Participants | 4206 Participants | 603 Participants | 613 Participants | 9863 Participants |
| Sex: Female, Male Male | 4366 Participants | 4088 Participants | 583 Participants | 567 Participants | 9604 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 8,807 | 16 / 8,294 | 12 / 8,161 | 9 / 7,582 | 0 / 1,186 | 1 / 1,180 | 0 / 1,171 | 3 / 1,168 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 1,303 / 8,807 | 1,489 / 8,294 | 1,618 / 8,161 | 1,374 / 7,582 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 339 / 1,186 | 304 / 1,180 |
| serious Total, serious adverse events | 133 / 8,807 | 217 / 8,294 | 180 / 8,161 | 176 / 7,582 | 22 / 1,186 | 35 / 1,180 | 64 / 1,171 | 53 / 1,168 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation
An MAAE was defined as an AE that led to an unscheduled visit (including a telemedicine visit) with a healthcare provider (\[HCP\], e.g., nurse, nurse practitioner, physician's assistant, physician). An SAE was defined as any event that resulted in death, was immediately life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect arising from a pregnancy conceived after receipt of study vaccine. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Day 1 to Day 92
Population: Safety Analysis Set, all participants who received any dose of study vaccine (ARCT-154 or placebo or ChAdOx1). Participants were analyzed according to the study vaccine received. As pre-specified, data are presented pooled per treatment received for Phase 1/2/3a/3b, and separately for ARCT-154 for Phase 3c. Overall number of participants analyzed = number of participants evaluable for the endpoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARCT-154 | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 6 Participants |
| ARCT-154 | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | SAEs | 133 Participants |
| ARCT-154 | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | MAAEs | 1132 Participants |
| Placebo | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | SAEs | 217 Participants |
| Placebo | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 18 Participants |
| Placebo | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | MAAEs | 1284 Participants |
| Phase 3c: ARCT-154 | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | SAEs | 22 Participants |
| Phase 3c: ARCT-154 | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | MAAEs | 148 Participants |
| Phase 3c: ARCT-154 | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Astra Zeneca COVID-19 vaccine | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 1 Participants |
| Astra Zeneca COVID-19 vaccine | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | SAEs | 35 Participants |
| Astra Zeneca COVID-19 vaccine | Number of Participants Reporting Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation | MAAEs | 146 Participants |
Primary
Number of Participants Reporting Solicited Local Adverse Reactions (ARs)
Solicited local ARs included injection site erythema, injection site pain, injection site induration/swelling, and injection site tenderness. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Within 7 days after Dose 1 and Dose 2 (up to Day 7 and 36)
Population: Reactogenicity Analysis Set, all participants who received any dose of study vaccine (ARCT-154 or placebo or ChAdOx1) and provided at least 1 reactogenicity diary report. As pre-specified, data are presented pooled per treatment received for Phase 1/2/3a/3b, and separately for ARCT-154 for Phase 3c. Overall number of participants analyzed = number of participants evaluable for the endpoint. Number analyzed = number of participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARCT-154 | Number of Participants Reporting Solicited Local Adverse Reactions (ARs) | Dose 1 | 4060 Participants |
| ARCT-154 | Number of Participants Reporting Solicited Local Adverse Reactions (ARs) | Dose 2 | 2852 Participants |
| Placebo | Number of Participants Reporting Solicited Local Adverse Reactions (ARs) | Dose 2 | 612 Participants |
| Placebo | Number of Participants Reporting Solicited Local Adverse Reactions (ARs) | Dose 1 | 909 Participants |
| Phase 3c: ARCT-154 | Number of Participants Reporting Solicited Local Adverse Reactions (ARs) | Dose 1 | 467 Participants |
| Phase 3c: ARCT-154 | Number of Participants Reporting Solicited Local Adverse Reactions (ARs) | Dose 2 | 286 Participants |
| Astra Zeneca COVID-19 vaccine | Number of Participants Reporting Solicited Local Adverse Reactions (ARs) | Dose 1 | 416 Participants |
| Astra Zeneca COVID-19 vaccine | Number of Participants Reporting Solicited Local Adverse Reactions (ARs) | Dose 2 | 183 Participants |
Primary
Number of Participants Reporting Solicited Systemic ARs
Solicited systemic ARs included arthralgia, chills, diarrhea, dizziness, fatigue, fever (categorized by measured body temperature), headache, myalgia, and nausea/vomiting. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Within 7 days after Dose 1 and Dose 2 (up to Day 7 and 36)
Population: Reactogenicity Analysis Set, all participants who received any dose of study vaccine (ARCT-154 or placebo or ChAdOx1) and provided at least 1 reactogenicity diary report. As pre-specified, data are presented pooled per treatment received for Phase 1/2/3a/3b, and separately for ARCT-154 for Phase 3c. Overall number of participants analyzed = number of participants evaluable for the endpoint. Number analyzed = number of participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARCT-154 | Number of Participants Reporting Solicited Systemic ARs | Dose 1 | 4375 Participants |
| ARCT-154 | Number of Participants Reporting Solicited Systemic ARs | Dose 2 | 3718 Participants |
| Placebo | Number of Participants Reporting Solicited Systemic ARs | Dose 2 | 1889 Participants |
| Placebo | Number of Participants Reporting Solicited Systemic ARs | Dose 1 | 2620 Participants |
| Phase 3c: ARCT-154 | Number of Participants Reporting Solicited Systemic ARs | Dose 2 | 477 Participants |
| Phase 3c: ARCT-154 | Number of Participants Reporting Solicited Systemic ARs | Dose 1 | 638 Participants |
| Astra Zeneca COVID-19 vaccine | Number of Participants Reporting Solicited Systemic ARs | Dose 2 | 331 Participants |
| Astra Zeneca COVID-19 vaccine | Number of Participants Reporting Solicited Systemic ARs | Dose 1 | 657 Participants |
Primary
Number of Participants Reporting Unsolicited Adverse Events (AEs)
Unsolicited AEs were defined as any spontaneously reported or discovered AE. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Approximately 28 days after Dose 1 and Dose 2 (Day 1 to Day 29 and Day 29 to Day 57)
Population: Safety Analysis Set, all participants who received any dose of study vaccine (ARCT-154 or placebo or ChAdOx1). Participants were analyzed according to the study vaccine received. As pre-specified, data are presented pooled per treatment received for Phase 1/2/3a/3b, and separately for ARCT-154 for Phase 3c. Overall number of participants analyzed = number of participants evaluable for the endpoint. Number analyzed = number of participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARCT-154 | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Dose 1 | 1323 Participants |
| ARCT-154 | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Dose 2 | 1232 Participants |
| Placebo | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Dose 2 | 1311 Participants |
| Placebo | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Dose 1 | 1198 Participants |
| Phase 3c: ARCT-154 | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Dose 1 | 260 Participants |
| Phase 3c: ARCT-154 | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Dose 2 | 226 Participants |
| Astra Zeneca COVID-19 vaccine | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Dose 1 | 252 Participants |
| Astra Zeneca COVID-19 vaccine | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Dose 2 | 225 Participants |
Primary
Number of Participants With a First Occurrence of Coronavirus Disease 2019 (COVID-19)
COVID-19 was defined as a positive SARS-CoV-2 test and at least one of the following that was a new or worsening finding: ⦁ Fever or chills ⦁ Cough ⦁ Shortness of breath or difficulty breathing ⦁ Fatigue ⦁ Muscle or body aches ⦁ Headache ⦁ New loss of taste or smell ⦁ Sore throat ⦁ Congestion or runny nose ⦁ Nausea or vomiting ⦁ Diarrhea Data are presented for the number of participants with a first occurrence of COVID-19 with no evidence of prior infection.
Time frame: Day 36 to Day 92
Population: Modified Intent-to-Treat (mITT) Analysis Set (Phase 3b), which included all participants who received all protocol-required doses of study vaccine up to the evaluation timepoint concerned, and who had no evidence of SARS-CoV-2 infection on Day 1 or up to 7 days after the 2nd study vaccination. As pre-specified, data are presented pooled per treatment received and for participants in Phase 3b only. Number of participants analyzed = those with evaluable data for this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARCT-154 | Number of Participants With a First Occurrence of Coronavirus Disease 2019 (COVID-19) | 200 Participants |
| Placebo | Number of Participants With a First Occurrence of Coronavirus Disease 2019 (COVID-19) | 440 Participants |
Primary
Number of Participants With Neutralizing Antibody (NAb) Responses
Data are presented for the number of participants with a NAb seroconversion response as determined by the surrogate virus neutralization test (sVNT). Seroconversion was defined as a ≥4-fold increase in antibody concentration from baseline.
Time frame: Day 57
Population: Immunogenicity Analysis Set, all participants who received all protocol required doses of vaccine up to evaluation timepoint, no evidence of prior severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection at Day 1, at least 1 valid post-vaccination immunogenicity assay result. As pre-specified, data is pooled per treatment received for participants in Phase 1, 2, 3a. Overall number of participants analyzed=number of participants evaluable for the endpoint at the specified timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARCT-154 | Number of Participants With Neutralizing Antibody (NAb) Responses | 658 Participants |
| Placebo | Number of Participants With Neutralizing Antibody (NAb) Responses | 1 Participants |
Secondary
Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies
Time frame: Days 1, 29, 57, 92
Population: Immunogenicity Analysis Set, all participants who received all protocol required doses of study vaccine up to evaluation timepoint, no evidence of prior SARS-CoV-2 infection at Day 1, with at least 1 valid post-vaccination immunogenicity assay result. As pre-specified, data is pooled per treatment received for participants in Phase 1, 2, 3a. Overall number of participants analyzed=participants evaluable for the endpoint. Number analyzed=participants with evaluable data at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| ARCT-154 | Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies | Day 1 | 0.3 units (U)/ milliliter (mL) |
| ARCT-154 | Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies | Day 29 | 2.1 units (U)/ milliliter (mL) |
| ARCT-154 | Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies | Day 57 | 20.3 units (U)/ milliliter (mL) |
| ARCT-154 | Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies | Day 92 | 11.9 units (U)/ milliliter (mL) |
| Placebo | Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies | Day 92 | 0.4 units (U)/ milliliter (mL) |
| Placebo | Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies | Day 1 | 0.3 units (U)/ milliliter (mL) |
| Placebo | Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies | Day 57 | 0.3 units (U)/ milliliter (mL) |
| Placebo | Geometric Mean Concentration of Spike Protein Immunoglobulin G (IgG) Binding Antibodies | Day 29 | 0.3 units (U)/ milliliter (mL) |
Secondary
Geometric Mean Fold Ratio of Spike Protein IgG Binding Antibodies
Time frame: Days 29, 57, 92
Population: Immunogenicity Analysis Set, all participants who received all protocol required doses of study vaccine up to evaluation timepoint, no evidence of prior SARS-CoV-2 infection at Day 1, with at least 1 valid post-vaccination immunogenicity assay result. As pre-specified, data is pooled per treatment received for participants in Phase 1, 2, 3a. Overall number of participants analyzed=participants evaluable for the endpoint. Number analyzed=participants with evaluable data at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| ARCT-154 | Geometric Mean Fold Ratio of Spike Protein IgG Binding Antibodies | Day 29 | 7.5 ratio |
| ARCT-154 | Geometric Mean Fold Ratio of Spike Protein IgG Binding Antibodies | Day 57 | 71.4 ratio |
| ARCT-154 | Geometric Mean Fold Ratio of Spike Protein IgG Binding Antibodies | Day 92 | 42.0 ratio |
| Placebo | Geometric Mean Fold Ratio of Spike Protein IgG Binding Antibodies | Day 29 | 1.0 ratio |
| Placebo | Geometric Mean Fold Ratio of Spike Protein IgG Binding Antibodies | Day 57 | 1.0 ratio |
| Placebo | Geometric Mean Fold Ratio of Spike Protein IgG Binding Antibodies | Day 92 | 1.5 ratio |
Secondary
Geometric Mean Fold Rise in SARS-CoV-2 Neutralizing Antibody Titers
Time frame: Days 29, 57, 92
Population: Immunogenicity Analysis Set, all participants who received all protocol required doses of study vaccine up to evaluation timepoint, no evidence of prior SARS-CoV-2 infection at Day 1, with at least 1 valid post-vaccination immunogenicity assay result. As pre-specified, data is pooled per treatment received for participants in Phase 1, 2, 3a. Overall number of participants analyzed=participants evaluable for endpoint. Number analyzed=participants with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| ARCT-154 | Geometric Mean Fold Rise in SARS-CoV-2 Neutralizing Antibody Titers | Day 29 | 4.0 Ratio |
| ARCT-154 | Geometric Mean Fold Rise in SARS-CoV-2 Neutralizing Antibody Titers | Day 57 | 14.5 Ratio |
| ARCT-154 | Geometric Mean Fold Rise in SARS-CoV-2 Neutralizing Antibody Titers | Day 92 | 13.7 Ratio |
| Placebo | Geometric Mean Fold Rise in SARS-CoV-2 Neutralizing Antibody Titers | Day 29 | 1.0 Ratio |
| Placebo | Geometric Mean Fold Rise in SARS-CoV-2 Neutralizing Antibody Titers | Day 57 | 1.0 Ratio |
| Placebo | Geometric Mean Fold Rise in SARS-CoV-2 Neutralizing Antibody Titers | Day 92 | 1.3 Ratio |
Secondary
Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies
Time frame: Days 1, 29, 57 and 92
Population: Immunogenicity Analysis Set, all participants who received all protocol required doses of study vaccine up to evaluation timepoint, no evidence of prior SARS-CoV-2 infection at Day 1, with at least 1 valid post-vaccination immunogenicity assay result. As pre-specified, data is pooled per treatment received for participants in Phase 1, 2, 3a. Overall number of participants analyzed=participants evaluable for endpoint. Number analyzed=participants with evaluable data at the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| ARCT-154 | Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies | Day 1 | 15.3 IU/mL |
| ARCT-154 | Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies | Day 29 | 60.7 IU/mL |
| ARCT-154 | Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies | Day 57 | 221.4 IU/mL |
| ARCT-154 | Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies | Day 92 | 209.6 IU/mL |
| Placebo | Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies | Day 92 | 20.3 IU/mL |
| Placebo | Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies | Day 1 | 15.2 IU/mL |
| Placebo | Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies | Day 57 | 15.2 IU/mL |
| Placebo | Geometric Mean Titers of SARS-CoV-2 Neutralizing Antibodies | Day 29 | 15.7 IU/mL |
Secondary
Number of Participants Seroconverting for Neutralizing Antibodies
Seroconversion was defined as a ≥4-fold increase in antibody concentration from baseline as measured by the sVNT test. Data are presented for the number of participants seroconverting for neutralizing antibodies.
Time frame: Days 29, 57 and 92
Population: Immunogenicity Analysis Set, all participants who received all protocol required doses of study vaccine up to evaluation timepoint, no evidence of prior SARS-CoV-2 infection at Day 1, with at least 1 valid post-vaccination immunogenicity assay result. As pre-specified, data is pooled per treatment received for participants in Phase 1, 2, 3a. Overall number of participants analyzed=participants evaluable for the endpoint. Number analyzed=participants with evaluable data at specified timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARCT-154 | Number of Participants Seroconverting for Neutralizing Antibodies | Day 29 | 388 Participants |
| ARCT-154 | Number of Participants Seroconverting for Neutralizing Antibodies | Day 57 | 658 Participants |
| ARCT-154 | Number of Participants Seroconverting for Neutralizing Antibodies | Day 92 | 571 Participants |
| Placebo | Number of Participants Seroconverting for Neutralizing Antibodies | Day 29 | 4 Participants |
| Placebo | Number of Participants Seroconverting for Neutralizing Antibodies | Day 57 | 1 Participants |
| Placebo | Number of Participants Seroconverting for Neutralizing Antibodies | Day 92 | 21 Participants |
Secondary
Number of Participants Seroconverting for Spike Protein IgG Binding Antibodies
Seroconversion was defined as a ≥4-fold increase in antibody concentration from baseline. Data are presented for the number of participants seroconverting for spike protein IgG binding antibodies.
Time frame: Days 29, 57, 92
Population: Immunogenicity Analysis Set, all participants who received all protocol-required doses of study vaccine up to evaluation timepoint, no evidence of prior SARS-CoV-2 infection at Day 1, with at least 1 valid post-vaccination immunogenicity assay result. As pre-specified, data is pooled per treatment received for participants in Phase 1, 2, 3a. Overall number of participants analyzed=participants evaluable for the endpoint. Number analyzed=participants with evaluable data at specified timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARCT-154 | Number of Participants Seroconverting for Spike Protein IgG Binding Antibodies | Day 29 | 527 Participants |
| ARCT-154 | Number of Participants Seroconverting for Spike Protein IgG Binding Antibodies | Day 57 | 698 Participants |
| ARCT-154 | Number of Participants Seroconverting for Spike Protein IgG Binding Antibodies | Day 92 | 652 Participants |
| Placebo | Number of Participants Seroconverting for Spike Protein IgG Binding Antibodies | Day 29 | 3 Participants |
| Placebo | Number of Participants Seroconverting for Spike Protein IgG Binding Antibodies | Day 57 | 3 Participants |
| Placebo | Number of Participants Seroconverting for Spike Protein IgG Binding Antibodies | Day 92 | 29 Participants |
Secondary
Number of Participants Seroconverting on Neutralizing Antibody Responses by Plaque Reduction Neutralization Test at 50% Reduction (PRNT50)
The plaque reduction neutralization test (PRNT) is a live virus assay. Neutralizing antibody titers were calculated as the highest serum dilution that resulted in 50% reduction in the number of virus plaques (PRNT50). Data presented is for the ancestral-clinical isolate variant. Data are presented for the number of participants that demonstrated seroconversion (as defined by 4-fold increase in neutralizing antibody concentration from baseline) on PRNT50.
Time frame: Days 29 and 57
Population: Immunogenicity Analysis Set, all participants who received all protocol-required doses of study vaccine up to evaluation timepoint, no evidence of prior SARS-CoV-2 infection at Day 1, with at least 1 valid post-vaccination immunogenicity assay result. As pre-specified, data is pooled per treatment received for participants in Phases 1 and 2. Overall number of participants analyzed=participants evaluable for the endpoint. Number analyzed=participants with evaluable data at specified timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARCT-154 | Number of Participants Seroconverting on Neutralizing Antibody Responses by Plaque Reduction Neutralization Test at 50% Reduction (PRNT50) | Day 29 | 17 Participants |
| ARCT-154 | Number of Participants Seroconverting on Neutralizing Antibody Responses by Plaque Reduction Neutralization Test at 50% Reduction (PRNT50) | Day 57 | 86 Participants |
| Placebo | Number of Participants Seroconverting on Neutralizing Antibody Responses by Plaque Reduction Neutralization Test at 50% Reduction (PRNT50) | Day 29 | 0 Participants |
| Placebo | Number of Participants Seroconverting on Neutralizing Antibody Responses by Plaque Reduction Neutralization Test at 50% Reduction (PRNT50) | Day 57 | 0 Participants |
Secondary
Number of Participants With a First Occurrence of COVID-19
Number of participants with a first occurrence of COVID-19 in participants with no evidence of prior infection.
Time frame: Day 1 to Day 92
Population: Intent-to-Treat (ITT) Analysis Set, which included all participants who received any dose of study vaccine. Participants were analyzed according to the vaccine to which the participant was randomly assigned. As pre-specified, data are presented for participants in the Phase 3b ITT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARCT-154 | Number of Participants With a First Occurrence of COVID-19 | 223 Participants |
| Placebo | Number of Participants With a First Occurrence of COVID-19 | 496 Participants |
Secondary
Number of Participants With a First Occurrence of COVID-19 Irrespective of Prior Infection
Number of participants with a first occurrence of COVID-19 irrespective of prior infection.
Time frame: Day 36 to Day 92
Population: Modified Intent-to-Treat (mITT) Analysis Set (pooled for Phases 1/2/3a/3b), including participants who received both doses of study vaccine and no infection between Day 1 and Day 35 but including those who were seropositive at baseline (Day 1). As pre-specified, data are presented pooled per treatment received for participants in Phases 1/2/3a/3b only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARCT-154 | Number of Participants With a First Occurrence of COVID-19 Irrespective of Prior Infection | 223 Participants |
| Placebo | Number of Participants With a First Occurrence of COVID-19 Irrespective of Prior Infection | 457 Participants |
Secondary
Number of Participants With a First Occurrence of Severe COVID-19
Number of participants with a first occurrence of severe COVID-19 in participants with no evidence of prior infection. Severe COVID-19 was defined as a positive SARS-CoV-2 test, symptoms per protocol-defined COVID-19 and any of the following: Clinical signs at rest indicative of severe systemic illness: - Respiratory rate ≥30 per minute, - Heart rate ≥125 per minute, - Oxygen saturation (SpO2) ≤93% on room air at sea level or partial pressure of oxygen (PO2)/fraction of inspired oxygen (FiO2) \<300 millimeter of mercury (mm Hg) - Respiratory failure (defined as needing high flow oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation \[ECMO\]); Evidence of shock: - Systolic blood pressure (SBP) \<90 mm Hg, or - Diastolic blood pressure (DBP) \<60 mm Hg, or requiring vasopressors, - Significant acute renal, hepatic, or neurologic dysfunction - Admission to an intensive care unit (ICU) - Death
Time frame: Day 36 to Day 92
Population: Modified Intent-to-Treat (mITT) Analysis Set (pooled for Phases 1/2/3a/3b), which included all participants who received all protocol-required doses of study vaccine up to the evaluation timepoint concerned, and who had no evidence of SARS-CoV-2 infection on Day 1 or up to 7 days after the 2nd study vaccination. As pre-specified, data are presented pooled per treatment received for participants in Phases 1/2/3a/3b only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARCT-154 | Number of Participants With a First Occurrence of Severe COVID-19 | 2 Participants |
| Placebo | Number of Participants With a First Occurrence of Severe COVID-19 | 43 Participants |
Secondary
Number of Participants With Death Due to COVID-19
Number of participants with death due to COVID-19 in participants with no evidence of prior infection.
Time frame: Day 36 to Day 92
Population: Modified Intent-to-Treat (mITT) Analysis Set (pooled for Phases 1/2/3a/3b), which included all participants who received all protocol-required doses of study vaccine up to the evaluation timepoint concerned, and who had no evidence of SARS-CoV-2 infection on Day 1 or up to 7 days after the 2nd study vaccination. As pre-specified, data are presented pooled per treatment received for participants in Phases 1/2/3a/3b only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARCT-154 | Number of Participants With Death Due to COVID-19 | 1 Participants |
| Placebo | Number of Participants With Death Due to COVID-19 | 9 Participants |