Anthrax
Conditions
Keywords
Anthrax, AV7909, BioThrax, Bacillus anthracis, Anthrax Vaccine Adsorbed, Post-exposure Prophylaxis, Vaccine, CPG 7909, Adjuvant
Brief summary
This study is designed to evaluate the lot consistency (using three consecutively manufactured lots), safety, and ability of the AV7909 anthrax vaccine to generate an immune response in healthy adults and compare the response to that induced by the currently licensed vaccine, BioThrax®, (Anthrax Vaccine Adsorbed; AVA) for post-exposure of anthrax disease.
Detailed description
This is a Phase 3, multicenter, randomized, double-blind, parallel-group trial designed to evaluate the lot consistency (using three consecutively manufactured lots), immunogenicity, and safety of AV7909 administered in healthy adults for an indication of postexposure prophylaxis (PEP) of anthrax. Healthy adults between 18 and 65 years of age (inclusive) will sign and date an informed consent form and then be screened for eligibility for participation in the study 2 to 28 days prior to randomization. Participants meeting the entry criteria will be randomized 2:2:2:1 to one of four study groups on Day 1. Randomization will be stratified by site. Participants will be evaluated for safety through Day 64 \[or the early withdrawal visit (EWV)\], as assessed by clinical laboratory tests (hematology, serum chemistry, and urinalysis), monitoring of Adverse Events (AE) including Serious Adverse Events (SAE) and Adverse Events of Special Interest (AESI), vital signs, and physical examinations. Adverse Events of Special Interest are adverse events associated with autoimmune disease as defined by the Center for Biologics Evaluation and Research, and might represent a safety signal for vaccine-associated autoimmunity. Reactogenicity (solicited systemic and injection site reactions) will be assessed daily by the participants using electronic diaries (e-diaries) after each vaccination. Information on the use of medications will be collected at each study visit. In addition, blood samples for auto-antibody assessment will be taken at Day 1 predose and Day 64 (or Early Withdrawal Visit). Participants who receive at least one dose of vaccine but who for any reason discontinue vaccinations prematurely will be asked to participate in the further planned study visits up to Day 64 for safety assessment only. Participants who receive at least one dose of vaccine will also be asked to participate in safety follow-up phone calls occurring on Day 43, Month 4, Month 7, Month 10, and Month 13 (nominally 0.5, 3, 6, 9, and 12 months after the last vaccination) to collect information on AEs, SAEs and any potential AESIs. Based on responses at these phone contacts, participants may be asked to return to the clinic for an unscheduled visit to provide blood samples for auto-antibody testing to investigate reports of potential AESIs. Independent safety oversight will be provided by a Data Safety Monitoring Board, which will be notified of significant AEs as determined by the Medical Monitor on an ongoing basis.
Interventions
BIOLOGICALAV7909
AV7909 consists of Anthrax Vaccine Adsorbed (AVA) drug substance and CPG 7909 adjuvant. AVA drug substance in AV7909 is similar in composition and manufactured using the same process as commercial BioThrax® vaccine. BioThrax is licensed for post-exposure prophylaxis of anthrax disease. CPG 7909 is an immunostimulatory synthetic oligodeoxynucleotide that functions as an adjuvant. It is designed to induce an enhanced immune response.
BIOLOGICALBioThrax
BioThrax vaccine (Anthrax Vaccine Adsorbed; AVA) is licensed for post-exposure prophylaxis of anthrax disease.
Sponsors
Biomedical Advanced Research and Development Authority
Emergent BioSolutions
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Written informed consent obtained from the participant (dated and signed). 2. Healthy condition as established by medical history and clinical examination before entering into the study. 3. A male or female aged 18 to 65 years, inclusive, at the time of informed consent. 4. Body mass index (BMI) ≤35.0 kg/m\^2 at Screening visit. 5. Have adequate venous access for phlebotomies. 6. For a woman of childbearing potential (WOCBP), negative serum pregnancy test at Screening and negative urine pregnancy test prevaccination on Day 1, not currently breastfeeding, and no intention to become pregnant during the study through Month 13. Every female participant is considered to be a WOCBP unless surgically sterile (bilateral oophorectomy or bilateral salpingectomy or hysterectomy) OR postmenopausal (defined as \>12 consecutive months without menses and screening follicle-stimulating hormone \>30 mIU/mL). Women who are not of childbearing potential are allowed to enroll if they are surgically sterile or postmenopausal as defined above.
Exclusion criteria
1. Use of any investigational or nonregistered product (drug, vaccine, device, or combination product) within 30 days preceding the dose of study vaccine, or planned use during the study through Month 13. 2. Positive test result on urine drug screen, any evidence of ongoing drug abuse or dependence (including alcohol), or recent history (over the past five years) of treatment for alcohol or drug abuse. 3. Chronic administration (defined as \>14 days) of immunosuppressants or other immune-modifying drugs (includes oral or parenteral corticosteroids, for example, a glucocorticoid dose exceeding 10 mg/day prednisone or equivalent) within six months prior to the vaccine dose; inhalation use (for example, for seasonal allergies) is permitted. 4. Planned administration of any commercially-available vaccine from seven days prior to the first study vaccination through two weeks after the last vaccination. 5. Previous anaphylactic reaction, severe systemic response, or serious hypersensitivity to a prior immunization or a known allergy to synthetic Oligodeoxynucleotides, aluminum, formaldehyde, benzethonium chloride (phemerol), or latex. 6. History of anthrax disease, suspected exposure to anthrax, or previous vaccination with any anthrax vaccine. 7. Have a tattoo/scar/birthmark or any other skin condition affecting the deltoid area that may interfere with injection site assessments. 8. A positive blood test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) HIV-1 or HIV-2 antibodies. 9. Any confirmed or suspected immunodeficiency condition (congenital or secondary) or autoimmune disease based on medical history and Physical Exam, for example, Guillain-Barré. 10. A family history of congenital or hereditary immunodeficiency. 11. Major congenital defects or serious chronic illness, including any cancer other than the following: a) any non-metastatic cancer (excluding hematologic malignancies) or melanoma of which the participant has been disease-free for at least five years and b) localized skin cancer, resected (including squamous cell and basal cell carcinomas). 12. Acute disease at the time of enrollment. Note that screening lab tests may be delayed to allow the resolution of a transient acute condition or the subject may be rescreened. 13. Any medical condition that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study. 14. Any planned elective surgery during the study through 12 months after the last vaccination. 15. Planned receipt of immunoglobulins and/or any blood products within the three months preceding study enrollment or at any point during the study period until after the final safety phone contact. 16. Woman of childbearing potential refusing to practice an adequate method of contraception from at least one month before Day 1 and continuing through Month 13. An adequate method of contraception is defined as abstinence from sexual intercourse; prior bilateral tubal ligation; monogamous relationship with a vasectomized partner (vasectomy performed at least six months prior to the participant's screening visit); or any of these forms of birth control: pill, intrauterine device (IUD), implantable or injectable contraceptive (for example, Norplant® or Depo-Provera®), removable device (for example, NuvaRing® or Evra® patch), or double-barrier method (condom with spermicide, diaphragm with spermicide). The Principal Investigator and/or designee will discuss with the participant the need to use adequate contraception consistently and correctly and document such conversation in the participant's chart. In addition, the Principal Investigator and/or designee will instruct the participant to call immediately if the selected contraception method is discontinued or if pregnancy is known or suspected. 17. Member or family member of the investigator site team. 18. Previously served in the military any time after 1990 and/or plan to enlist in the military at any time from screening through the final telephone contact.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Serious Adverse Events | Day 1 though Day 394 | Number of AV7909 participants or BioThrax participants who received at least one vaccination and reported serious adverse event(s) (SAEs) from the time of the first vaccination on Day 1 through Day 394. |
| Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) 50% Neutralization Factor (NF50) at Day 64 | Day 64 (seven weeks after second AV7909 vaccination) | GMT of TNA NF50 at Day 64 in AV7909 study groups (Lots 1, 2 and 3) and BioThrax group. The outcome measure in AV7909 study groups was assessed for AV7909 lot-to-lot consistency, which was based on GMT TNA NF50 response at Day 64, wherein the 95% confidence interval (CI) for ratios of geometric mean titer (GMT) of TNA NF50 at Day 64 (seven weeks after second AV7909 vaccination) for each of the three AV7909 lot-to-lot comparisons had to be within equivalence margin of 0.5 and 2.0. |
| Percentage of Participants in AV7909 Lot 1, Lot 2 and Lot 3 Groups Achieving a TNA NF50 ≥0.56 on Day 64 | Day 64 (seven weeks after second AV7909 vaccination) | Proportion of participants with TNA NF50 ≥0.56 at Day 64 in each AV7909 study groups (Lot 1, Lot 2, Lot 3). The assessment of the immune response in each study group was pre-defined as the lower bound of the two-sided 95% CI to be ≥40% for the percentage of AV7909 participants in each of the three lots achieving a TNA NF50 ≥0.56 at seven weeks after second AV7909 vaccination (Day 64). |
| Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.56 on Day 64 | Day 64 (seven weeks after second AV7909 vaccination) | Percentage of AV7909 participants (from all three AV7909 study groups pooled) achieving a TNA NF50 ≥0.56 on Day 64 (seven weeks after second AV7909 vaccination). The assessment of the immune response in AV7909 participants was pre-defined as the lower bound of the two-sided 95% CI for proportion of AV7909 participants with TNA NF50 ≥0.56 at Day 64 ≥40%. |
| Percentage of AV7909 Participants and BioThrax Participants With TNA NF50 ≥0.29 at Day 64 | Day 64 (seven weeks after second AV7909 vaccination; five weeks after third BioThrax vaccination) | Proportion of AV7909 participants (in each AV7909 study groups) and BioThrax participants who achieved TNA NF50 ≥0.29 at Day 64. Non-inferiority of AV7909 vaccine to BioThrax vaccine at Day 64 was assessed as determined by the two-sided lower bound for the 95% CI of the difference in the percentage of AV7909 participants (three lots pooled) with a TNA NF50 ≥0.29 and the percentage of BioThrax participants with a TNA NF50 ≥0.29 being greater than -15%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.15 on Day 29. | Day 29 (two weeks after second AV7909 vaccination) | Proportion of AV7909 participants (in each AV7909 study group) who achieved TNA NF50 ≥0.15 at Day 29 (two weeks after second AV7909 vaccination). Assessment of the lower bound of the two-sided 95% CI to be ≥67% for the percentage of AV7909 participants in AV7909 study groups 1-3 (Pooled AV7909) achieving a TNA NF50 ≥0.15 on Day 29 was performed. |
| Incidence of Adverse Events | Day 1 through Day 64 | Number of AV7909 or BioThrax participants who received at least one vaccination and had at least one adverse event reported from the time of the first vaccination on Day 1 through Day 64. |
| Incidence of Adverse Events of Special Interest (Events of Autoimmune Etiology) | Day 1 through Day 394 | Incidence of adverse events of special interest (AESIs; events of autoimmune etiology) from the time of the first vaccination on Day 1 through Day 394 in participants who received at least one dose of AV7909 (Lot 1, Lot 2 or Lot 3) or BioThrax vaccines. |
| Incidence of Solicited Systemic Reactogenicity Events | Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day) | Incidence of any solicited systemic reactogenicity reaction after any AV7909 or BioThrax vaccination. |
| Incidences of Solicited Injection Site Reactogenicity Events | Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day) | Incidence of any solicited injection site reactogenicity reaction after any AV7909 (Lots 1, 2 or 3) or BioThrax vaccination. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AV7909 Lot 1 Eligible participants randomized to receive AV7909 Lot 1. | 1,103 |
| AV7909 Lot 2 Eligible participants randomized to receive AV7909 Lot 2. | 1,103 |
| AV7909 Lot 3 Eligible participants randomized to receive AV7909 Lot 3. | 1,098 |
| BioThrax Eligible participants randomized to receive BioThrax vaccine. | 558 |
| Total | 3,862 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 |
| Overall Study | Death | 2 | 2 | 2 | 0 |
| Overall Study | Lost to Follow-up | 41 | 52 | 45 | 17 |
| Overall Study | Not Treated | 3 | 1 | 1 | 0 |
| Overall Study | Other - Various | 4 | 1 | 1 | 0 |
| Overall Study | Physician Decision | 2 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 18 | 21 | 12 | 4 |
Baseline characteristics
| Characteristic | AV7909 Lot 1 | AV7909 Lot 2 | AV7909 Lot 3 | BioThrax | Total |
|---|---|---|---|---|---|
| Age, Continuous | 39.0 years STANDARD_DEVIATION 13 | 39.2 years STANDARD_DEVIATION 13.1 | 38.9 years STANDARD_DEVIATION 12.8 | 38.6 years STANDARD_DEVIATION 12.4 | 39.0 years STANDARD_DEVIATION 12.9 |
| Age, Customized 18-30 years | 341 Participants | 355 Participants | 352 Participants | 176 Participants | 1224 Participants |
| Age, Customized 31-50 years | 502 Participants | 470 Participants | 488 Participants | 269 Participants | 1729 Participants |
| Age, Customized 51-65 years | 260 Participants | 278 Participants | 258 Participants | 113 Participants | 909 Participants |
| Body Mass Index | 26.9 kg/m^2 STANDARD_DEVIATION 4.3 | 27.3 kg/m^2 STANDARD_DEVIATION 4.3 | 27.2 kg/m^2 STANDARD_DEVIATION 4.3 | 27.3 kg/m^2 STANDARD_DEVIATION 4.2 | 27.1 kg/m^2 STANDARD_DEVIATION 4.3 |
| Race/Ethnicity, Customized Ethnicity: Hispanic or Latino | 177 Participants | 156 Participants | 142 Participants | 98 Participants | 573 Participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 910 Participants | 938 Participants | 945 Participants | 450 Participants | 3243 Participants |
| Race/Ethnicity, Customized Ethnicity: Not Reported | 12 Participants | 7 Participants | 3 Participants | 6 Participants | 28 Participants |
| Race/Ethnicity, Customized Ethnicity: Unknown | 4 Participants | 2 Participants | 8 Participants | 4 Participants | 18 Participants |
| Race/Ethnicity, Customized Race : American Indian or Alaska Native | 4 Participants | 4 Participants | 5 Participants | 2 Participants | 15 Participants |
| Race/Ethnicity, Customized Race : Asian | 17 Participants | 18 Participants | 24 Participants | 15 Participants | 74 Participants |
| Race/Ethnicity, Customized Race : Black or African American | 170 Participants | 186 Participants | 191 Participants | 89 Participants | 636 Participants |
| Race/Ethnicity, Customized Race : More than One Race | 22 Participants | 20 Participants | 14 Participants | 9 Participants | 65 Participants |
| Race/Ethnicity, Customized Race : Native Hawaiian or Other Pacific Islander | 2 Participants | 5 Participants | 3 Participants | 1 Participants | 11 Participants |
| Race/Ethnicity, Customized Race : Other | 8 Participants | 3 Participants | 5 Participants | 1 Participants | 17 Participants |
| Race/Ethnicity, Customized Race : Unknown | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 10 Participants |
| Race/Ethnicity, Customized Race : White | 878 Participants | 865 Participants | 852 Participants | 439 Participants | 3034 Participants |
| Region of Enrollment United States | 1103 Participants | 1103 Participants | 1098 Participants | 558 Participants | 3862 Participants |
| Sex: Female, Male Female | 650 Participants | 615 Participants | 647 Participants | 308 Participants | 2220 Participants |
| Sex: Female, Male Male | 453 Participants | 488 Participants | 451 Participants | 250 Participants | 1642 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 1,100 | 2 / 1,102 | 2 / 1,097 | 0 / 558 |
| other Total, other adverse events | 193 / 1,100 | 189 / 1,102 | 120 / 1,097 | 110 / 558 |
| serious Total, serious adverse events | 21 / 1,100 | 16 / 1,102 | 21 / 1,097 | 4 / 558 |
Outcome results
Primary
Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) 50% Neutralization Factor (NF50) at Day 64
GMT of TNA NF50 at Day 64 in AV7909 study groups (Lots 1, 2 and 3) and BioThrax group. The outcome measure in AV7909 study groups was assessed for AV7909 lot-to-lot consistency, which was based on GMT TNA NF50 response at Day 64, wherein the 95% confidence interval (CI) for ratios of geometric mean titer (GMT) of TNA NF50 at Day 64 (seven weeks after second AV7909 vaccination) for each of the three AV7909 lot-to-lot comparisons had to be within equivalence margin of 0.5 and 2.0.
Time frame: Day 64 (seven weeks after second AV7909 vaccination)
Population: Participants that met protocol-defined immunogenicity criteria from AV7909 Lot 1 group (n=878), AV7909 Lot 2 group (n=896), AV7909 Lot 3 group (n=896) and BioThrax group (n=454) are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AV7909 Lot 1 | Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) 50% Neutralization Factor (NF50) at Day 64 | 0.753 Titer (TNA NF50) |
| AV7909 Lot 2 | Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) 50% Neutralization Factor (NF50) at Day 64 | 0.746 Titer (TNA NF50) |
| AV7909 Lot 3 | Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) 50% Neutralization Factor (NF50) at Day 64 | 0.718 Titer (TNA NF50) |
| BioThrax | Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) 50% Neutralization Factor (NF50) at Day 64 | 0.335 Titer (TNA NF50) |
95% CI: [0.93, 1.1]
95% CI: [0.96, 1.14]
95% CI: [0.95, 1.13]
Primary
Incidence of Serious Adverse Events
Number of AV7909 participants or BioThrax participants who received at least one vaccination and reported serious adverse event(s) (SAEs) from the time of the first vaccination on Day 1 through Day 394.
Time frame: Day 1 though Day 394
Population: For the relative risk of SAE incidence analysis, participants from all three AV7909 study groups (Lot 1, Lot 2, Lot 3) since AV7909 lots 1, 2 and 3 were considered the same product (consecutively manufactured, and released with the same product specifications); hence, it was pre-defined to combine SAE data from participants across the three AV7909 lots for SAE relative risk analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AV7909 Lot 1 | Incidence of Serious Adverse Events | 21 Participants |
| AV7909 Lot 2 | Incidence of Serious Adverse Events | 16 Participants |
| AV7909 Lot 3 | Incidence of Serious Adverse Events | 21 Participants |
| BioThrax | Incidence of Serious Adverse Events | 4 Participants |
95% CI: [0.9, 6.5]
Primary
Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.56 on Day 64
Percentage of AV7909 participants (from all three AV7909 study groups pooled) achieving a TNA NF50 ≥0.56 on Day 64 (seven weeks after second AV7909 vaccination). The assessment of the immune response in AV7909 participants was pre-defined as the lower bound of the two-sided 95% CI for proportion of AV7909 participants with TNA NF50 ≥0.56 at Day 64 ≥40%.
Time frame: Day 64 (seven weeks after second AV7909 vaccination)
Population: Data from participants who met protocol-defined criteria for inclusion in the immunogenicity population from all three AV7909 study groups (i.e., pooled AV7909; n=2670) were used for the analysis. The pre-defined success criteria (lower bound of the two-sided 95% CI to be ≥40% for the percentage of participants achieving a TNA NF50 ≥0.56 on Day 64) was not applicable for BioThrax participants, therefore BioThrax group was not included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AV7909 Lot 1 | Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.56 on Day 64 | 66.3 percentage of participants |
95% CI: [64.5, 68.1]
Primary
Percentage of AV7909 Participants and BioThrax Participants With TNA NF50 ≥0.29 at Day 64
Proportion of AV7909 participants (in each AV7909 study groups) and BioThrax participants who achieved TNA NF50 ≥0.29 at Day 64. Non-inferiority of AV7909 vaccine to BioThrax vaccine at Day 64 was assessed as determined by the two-sided lower bound for the 95% CI of the difference in the percentage of AV7909 participants (three lots pooled) with a TNA NF50 ≥0.29 and the percentage of BioThrax participants with a TNA NF50 ≥0.29 being greater than -15%.
Time frame: Day 64 (seven weeks after second AV7909 vaccination; five weeks after third BioThrax vaccination)
Population: Data from participants who met protocol-defined criteria for inclusion in the immunogenicity population from each AV7909 study group (Lot 1 n=878; Lot 2 n=896; Lot 3 n=896) and BioThrax group (n=454) were used in the analysis. For the non-inferiority assessment, participants who met pre-defined criteria (achievement of TNA NF50 ≥0.29 at Day 64) from the pooled AV7909 study groups 1-3 (AV7909 Lot 1, Lot 2, Lot 3; i.e., Pooled AV7909) and BioThrax group were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AV7909 Lot 1 | Percentage of AV7909 Participants and BioThrax Participants With TNA NF50 ≥0.29 at Day 64 | 86.9 percentage of participants |
| AV7909 Lot 2 | Percentage of AV7909 Participants and BioThrax Participants With TNA NF50 ≥0.29 at Day 64 | 87.2 percentage of participants |
| AV7909 Lot 3 | Percentage of AV7909 Participants and BioThrax Participants With TNA NF50 ≥0.29 at Day 64 | 85.8 percentage of participants |
| BioThrax | Percentage of AV7909 Participants and BioThrax Participants With TNA NF50 ≥0.29 at Day 64 | 62.1 percentage of participants |
95% CI: [20, 29.2]
Primary
Percentage of Participants in AV7909 Lot 1, Lot 2 and Lot 3 Groups Achieving a TNA NF50 ≥0.56 on Day 64
Proportion of participants with TNA NF50 ≥0.56 at Day 64 in each AV7909 study groups (Lot 1, Lot 2, Lot 3). The assessment of the immune response in each study group was pre-defined as the lower bound of the two-sided 95% CI to be ≥40% for the percentage of AV7909 participants in each of the three lots achieving a TNA NF50 ≥0.56 at seven weeks after second AV7909 vaccination (Day 64).
Time frame: Day 64 (seven weeks after second AV7909 vaccination)
Population: Data from participants that met protocol-defined criteria for inclusion in the immunogenicity population are included in the analysis; i.e., AV7909 Lot 1 n=878; AV7909 Lot 2 n=896; AV7909 Lot 3 n=896. Pre-defined success criteria (lower bound of the two-sided 95% CI to be ≥40% for the percentage of participants achieving a TNA NF50 ≥0.56 at Day 64) was only applicable for AV7909 study groups and not for BioThrax group; therefore, BioThrax group is not included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AV7909 Lot 1 | Percentage of Participants in AV7909 Lot 1, Lot 2 and Lot 3 Groups Achieving a TNA NF50 ≥0.56 on Day 64 | 68.5 percentage of participants |
| AV7909 Lot 2 | Percentage of Participants in AV7909 Lot 1, Lot 2 and Lot 3 Groups Achieving a TNA NF50 ≥0.56 on Day 64 | 66.1 percentage of participants |
| AV7909 Lot 3 | Percentage of Participants in AV7909 Lot 1, Lot 2 and Lot 3 Groups Achieving a TNA NF50 ≥0.56 on Day 64 | 64.5 percentage of participants |
Secondary
Incidence of Adverse Events
Number of AV7909 or BioThrax participants who received at least one vaccination and had at least one adverse event reported from the time of the first vaccination on Day 1 through Day 64.
Time frame: Day 1 through Day 64
Population: Data from participants who received at least one dose of AV7909 vaccine Lot 1 (n=1100), Lot 2 (n=1102) or Lot 3 (n=1097) or BioThrax vaccine (n=558) are included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AV7909 Lot 1 | Incidence of Adverse Events | 410 Participants |
| AV7909 Lot 2 | Incidence of Adverse Events | 400 Participants |
| AV7909 Lot 3 | Incidence of Adverse Events | 408 Participants |
| BioThrax | Incidence of Adverse Events | 210 Participants |
Secondary
Incidence of Adverse Events of Special Interest (Events of Autoimmune Etiology)
Incidence of adverse events of special interest (AESIs; events of autoimmune etiology) from the time of the first vaccination on Day 1 through Day 394 in participants who received at least one dose of AV7909 (Lot 1, Lot 2 or Lot 3) or BioThrax vaccines.
Time frame: Day 1 through Day 394
Population: Data from participants who received at least one dose of AV7909 vaccine (Lot 1, Lot 2 or Lot 3) or BioThrax vaccine are used in the analysis. Since AV7909 lots 1, 2 and 3 were considered the same product (consecutively manufactured, and released with the same product specifications), it was pre-defined to combine AESI data from participants across the three AV7909 lots for AESI relative risk analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AV7909 Lot 1 | Incidence of Adverse Events of Special Interest (Events of Autoimmune Etiology) | 5 Participants |
| AV7909 Lot 2 | Incidence of Adverse Events of Special Interest (Events of Autoimmune Etiology) | 4 Participants |
| AV7909 Lot 3 | Incidence of Adverse Events of Special Interest (Events of Autoimmune Etiology) | 6 Participants |
| BioThrax | Incidence of Adverse Events of Special Interest (Events of Autoimmune Etiology) | 2 Participants |
95% CI: [0.3, 5]
Secondary
Incidence of Solicited Systemic Reactogenicity Events
Incidence of any solicited systemic reactogenicity reaction after any AV7909 or BioThrax vaccination.
Time frame: Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day)
Population: Data from participants (solicited systemic reactogenicity events after any vaccination) who received at least one dose of AV7909 vaccine or BioThrax vaccine are included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AV7909 Lot 1 | Incidence of Solicited Systemic Reactogenicity Events | 930 Participants |
| AV7909 Lot 2 | Incidence of Solicited Systemic Reactogenicity Events | 923 Participants |
| AV7909 Lot 3 | Incidence of Solicited Systemic Reactogenicity Events | 906 Participants |
| BioThrax | Incidence of Solicited Systemic Reactogenicity Events | 438 Participants |
Secondary
Incidences of Solicited Injection Site Reactogenicity Events
Incidence of any solicited injection site reactogenicity reaction after any AV7909 (Lots 1, 2 or 3) or BioThrax vaccination.
Time frame: Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day)
Population: Data from participants who received at least one dose of AV7909 or BioThrax dose are included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AV7909 Lot 1 | Incidences of Solicited Injection Site Reactogenicity Events | 1009 Participants |
| AV7909 Lot 2 | Incidences of Solicited Injection Site Reactogenicity Events | 1010 Participants |
| AV7909 Lot 3 | Incidences of Solicited Injection Site Reactogenicity Events | 1013 Participants |
| BioThrax | Incidences of Solicited Injection Site Reactogenicity Events | 525 Participants |
Secondary
Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.15 on Day 29.
Proportion of AV7909 participants (in each AV7909 study group) who achieved TNA NF50 ≥0.15 at Day 29 (two weeks after second AV7909 vaccination). Assessment of the lower bound of the two-sided 95% CI to be ≥67% for the percentage of AV7909 participants in AV7909 study groups 1-3 (Pooled AV7909) achieving a TNA NF50 ≥0.15 on Day 29 was performed.
Time frame: Day 29 (two weeks after second AV7909 vaccination)
Population: Data from participants who met protocol-defined criteria for inclusion in the immunogenicity population (AV7909 study groups 1-3) were used in the analysis. The pre-defined success criteria (lower bound of the two-sided 95% CI to be ≥67% for the percentage of participants achieving a TNA NF50 ≥0.15 on Day 29) was not applicable for BioThrax, therefore BioThrax group was not included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AV7909 Lot 1 | Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.15 on Day 29. | 98.1 percentage of participants |
| AV7909 Lot 2 | Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.15 on Day 29. | 97.9 percentage of participants |
| AV7909 Lot 3 | Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.15 on Day 29. | 97.4 percentage of participants |
95% CI: [97.2, 98.3]