Healthy
Conditions
Keywords
Anthrax, Vaccine, Immunogenicity, Reactogenicity
Brief summary
Anthrax Clinical Trial Objectives: To assess whether: * Anthrax vaccine (AVA or BioThrax, BioPort Corp. Lansing MI) administered by the intramuscular (IM) route elicits antibody responses that are not inferior (i.e., non-inferior) to that achieved by the currently licensed schedule. * BioThrax administered by the IM route and containing fewer numbers of doses elicits antibody responses that are not inferior (i.e., non-inferior) to that achieved by the currently licensed schedule. * Differences in reactogenicity exist between the IM and subcutaneous (SQ) administration of BioThrax. Additionally for the final report we will assess whether: * Occurrence of adverse events following AVA administration is influenced by selected risk factors.
Detailed description
This study is a 43-month prospective, randomized, double-blind, placebo-controlled comparison of immunogenicity and reactogenicity elicited by BioThrax given by different routes of administration (SQ versus IM) and dosing regimens (as many as 8 doses versus as few as 4 doses). Sterile saline is used as the placebo where doses are dropped in regimens using AVA, and in the all-placebo study group. This study is conducted among a total of 1564 healthy adult men and women (18 to 61 years of age) at five sites in the United States. Participants were randomized into one of 6 study groups with 260 participants per group. One group receives BioThrax given as currently licensed (SQ with 6 doses followed by annual boosters); another group is given placebo IM (130 participants) or SQ (130 participants) in the currently licensed dosing regimen. The four other groups receive BioThrax IM in modified dosing regimens; placebo is given when a dose of BioThrax is omitted from the licensed dosing regimen. There are a total of 25 required visits for this study, during which all participants receive an injection of vaccine or placebo (8 injections total), have a blood sample drawn (16 or 17 total), and have an in-clinic examination for adverse events (22 total). Immunogenicity is assessed by assaying 16 serial blood samples obtained from all participants and a 17th sample from a subset of participants before vaccination and at other specified times. Total anti-protective antigen IgG antibody (anti-PA IgG) is quantified using a standardized and validated enzyme-linked immunosorbent assay (ELISA); the primary study endpoints are 4-fold rise in antibody titer and antibody concentration relative to the pre-vaccination titers or assay reactivity threshold. A subset of serum samples is also assayed in an in vitro toxin neutralization assay (TNA) to measure the functional activity of anti-BioThrax antibodies. The kinetics of the immune response to BioThrax are examined at 3 time points in the study and blood samples from a subset of participants will be further tested in correlates of protection and immunogenetics substudies. All adverse events (AEs), including vaccine reactogenicity, are actively monitored. While all AEs will be ascertained among study participants, several endpoints will be defined based on the likelihood of their occurrence and/or their clinical importance. Of primary interest is the occurrence of local AEs such as warmth, tenderness, itching, pain, arm motion limitation, erythema, induration, nodule, and bruise. Systemic AEs such as fever, fatigue, muscle ache, headache, temperature, and painful axillary adenopathy are also evaluated. This study is expected to provide the basis for consideration of change in route of BioThrax administration from SQ to IM and reduction in number of vaccine doses required for primary and booster immunization. There is an interim analysis of data collected through each participant's first 7 months of this study for consideration in changing the route of BioThrax administration from SQ to IM, and elimination of the 2 week vaccine priming dose. At the end of the study, the Sponsor will present the entire results of the trial to FDA for consideration in elimination of additional doses from the licensed BioThrax schedule. At that time, the Sponsor will also supplement these data with results from parallel non-human primate challenge studies and additional research on immunologic correlates of protection.
Interventions
BIOLOGICALAnthrax Vaccine Adsorbed
BIOLOGICALSaline injection
Sponsors
Walter Reed Army Institute of Research (WRAIR)
Baylor College of Medicine
University of Alabama at Birmingham
Emory University
Mayo Clinic
Centers for Disease Control and Prevention
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 61 Years
Healthy volunteers
Yes
Inclusion criteria
Read/sign Informed Consent Document; Female or male, 18 to 61 years old (up to 62nd birthday); Females must agree to exercise adequate birth control from the time of the screening procedures to one month after the last vaccination; willingness/ability to return for all follow-up visits and blood collections for the duration of the study; ability to understand/comply with planned study procedures; agree to complete the Participant Diary (Appendix G) and to report concomitant medications and AEs during the study period; thave two intact upper arms with sufficient subcutaneous and intramuscular tissue in the deltoid regions for vaccine administration.Potential participants with a history of the following conditions remain eligible for study enrollment: gestational diabetes; treated, controlled, uncomplicated hypertension; treated hypo- or hyperthyroidism; cured nonmetastatic cancer; disease-free for 5 years (excluding hematologic malignancies); localized skin cancer, resected (including squamous cell and basal cell carcinomas, participants with a history of melanoma must be disease-free for 5 years); exercise-induced bronchospasm; mild asthma: use of inhalers only for control of symptoms is acceptable (Persons who have required hospitalization for asthma within the previous 2 years or those who require chronic or frequent oral/parenteral steroids will not be eligible; use of low to medium doses of inhaled steroids; history of coronary artery disease, asymptomatic (NYHA Function Class I), on a stable medical regimen. Persons meeting these criteria must be at least 2 years post-myocardial infarction, cardiac bypass surgery, and/or percutaneous coronary intervention (e.g., angioplasty, stent placement, etc) in order to qualify. Persons with a history of cardiac disease must be under the care of a physician.
Exclusion criteria
Prior history of anthrax or immunization against anthrax; Known allergy to aluminum hydroxide, formaldehyde, benzethonium chloride, or latex; Pregnant/plans to become pregnant for duration of study/does not agree to use adequate birth control from the time of screening procedures to one month after last vaccination; Used cytotoxic therapy in previous 5 years; Cardiovascular disease with significant likelihood of progression over 5 years; Moderate to severe asthma, chronic obstructive pulmonary disease, other significant pulmonary disease; using high doses of inhaled steroids; Clinically recognized hepatic or renal insufficiency; Inflammatory, vasculitic, or rheumatic disease including systemic lupus erythematosis, polymyalgia rheumatica and rheumatoid arthritis, scleroderma; Known HIV, hepatitis B or hepatitis C infection; Other conditions known to produce or be associated with immune suppression; Neuropathy or other evolving neurologic condition; Unstable/moderate to severe mental illness; Ongoing drug abuse/dependence (including alcohol); Seizure disorder; Active malignancy or history of metastatic or hematologic malignancy; current diabetes; Anyone who plans to receive within 60 days of study entry: cytotoxic therapy, experimental products, a live vaccine outside this trial, immunosuppressive therapy, parenteral immunoglobulin or blood products; Anyone who plans to receive an inactivated vaccine outside this trial within 42 days after study entry;: experimental products, a live vaccine outside this trial, immunosuppressive therapy; Anyone who received an inactivated vaccine outside this trial within 14 days prior to study entry, parenteral immunoglobulin or blood products within three months of study. In addition to conditions listed above, temporary exclusion would result from moderate or severe illness and/or oral temperature \>100.4˚F within 3 days of injection or chronic condition that, in opinion of investigator, would render injection unsafe or would interfere with evaluations.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local AEs | 4 weeks after each injection | warmth, tenderness, itching, pain, arm motion limitation, erythema, induration, nodule, and bruise. The number of injections analyzable varies for each event based on the presence or absence of reported data. |
| Systemic AEs | 4 weeks after each injection | Fatigue, Muscle Ache, Headache, Fever, Tender Axillary Lymphnode The number of injections analyzable varies for each event based on the presence or absence of reported data. |
| Anti-protective Antigen IgG Geometric Mean Concentration | 4 weeks after the m1, m6 and m42 injections | Geometric mean of the Anti-PA IgG Concentration measured in μg/mL. The lower limit of quantification (LLOQ) is 3.7, results below the LLOQ have been replaced by 1/2 LLOQ (1.85) before taking the geometric mean. |
| Anti-protective Antigen IgG Geometric Mean Titer | 4 weeks after the m1, m6 and m42 injections | Geometric mean of the Dilutional Titer. The Dilutional Titer is the reciprocal of the dilution at which the anti-PA IgG response reaches a threshold. The lower limit of quantification (LLOQ) is 58, results below the LLOQ have been replaced by 1/2 LLOQ (29) before taking the geometric mean. |
| 4-fold Rise in Anti-protective Antigen IgG Titer Response | 4 weeks after the m1, m6 and m42 injections | Percent of participants who achieved a 4-fold or greater rise in anti-PA IgG Titer relative to the pre-vaccination level at month 0. The Dilutional Titer is the reciprocal of the dilution at which the anti-PA IgG response reaches a threshold. The lower limit of quantification (LLOQ) is 58, results below the LLOQ have been replaced by LLOQ (58) before calculating the fold response. Thus the lowest titer that can achieve 4-fold rise is 4\*58 = 232. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TNA ED50 Titer | 4 weeks after the m1, m6 and m42 injections | Geometric mean of the ED50. The ED50 is the reciprocal of the dilution at which patient serum neutralizes 50% of a dose of anthrax lethal toxin (ED50). The lower limit of quantification (LLOQ) for this assay is 36, results below the LLOQ have been replaced with 1/2 LLOQ (18) before taking the geometric mean. Note that this secondary endpoint was only performed on \ 47% of the participants. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anthrax Vaccine Adsorbed 8-SQ receive 8 injections of Anthrax Vaccine Adsorbed injected SQ at the same points as the original licensure: 0m, 2weeks, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. | 259 |
| Anthrax Vaccine Adsorbed 8-IM receive 8 injections of Anthrax Vaccine Adsorbed IM administered at 0m, 2weeks, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. | 262 |
| Anthrax Vaccine Adsorbed 7-IM receive 7 injections of Anthrax Vaccine Adsorbed IM administered at 0m, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. | 256 |
| Anthrax Vaccine Adsorbed 5-IM receive 5 injections of Anthrax Vaccine Adsorbed IM administered at 0m, 1m, 6m, and 2 boosters - 30m and 42m. | 258 |
| Anthrax Vaccine Adsorbed 4-IM receive 4 injections of Anthrax Vaccine Adsorbed IM; months 0, 2, 6 and a booster at month 42 | 268 |
| Saline Placebo IM or SQ Saline injections to be administered either IM or SQ at 0m, 2weeks, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. | 260 |
| Total | 1,563 |
Baseline characteristics
| Characteristic | Anthrax Vaccine Adsorbed 8-SQ | Anthrax Vaccine Adsorbed 8-IM | Anthrax Vaccine Adsorbed 7-IM | Anthrax Vaccine Adsorbed 5-IM | Anthrax Vaccine Adsorbed 4-IM | Saline Placebo IM or SQ | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized Age <30 | 77 participants | 63 participants | 75 participants | 77 participants | 72 participants | 75 participants | 439 participants |
| Age, Customized Age 30-39 | 42 participants | 57 participants | 77 participants | 65 participants | 60 participants | 60 participants | 361 participants |
| Age, Customized Age 40-49 | 91 participants | 87 participants | 54 participants | 64 participants | 91 participants | 73 participants | 460 participants |
| Age, Customized Age 50-61 | 49 participants | 55 participants | 50 participants | 52 participants | 45 participants | 52 participants | 303 participants |
| Race/Ethnicity, Customized Ethnicity: Hispanic | 13 participants | 12 participants | 9 participants | 15 participants | 12 participants | 9 participants | 70 participants |
| Race/Ethnicity, Customized Ethnicity:Non-Hispanic | 246 participants | 250 participants | 247 participants | 243 participants | 256 participants | 251 participants | 1493 participants |
| Race/Ethnicity, Customized Race: Black | 47 participants | 48 participants | 49 participants | 62 participants | 59 participants | 59 participants | 324 participants |
| Race/Ethnicity, Customized Race: Other | 13 participants | 17 participants | 13 participants | 13 participants | 8 participants | 16 participants | 80 participants |
| Race/Ethnicity, Customized Race: White | 199 participants | 197 participants | 194 participants | 183 participants | 201 participants | 185 participants | 1159 participants |
| Sex: Female, Male Female | 134 Participants | 135 Participants | 132 Participants | 131 Participants | 136 Participants | 132 Participants | 800 Participants |
| Sex: Female, Male Male | 125 Participants | 127 Participants | 124 Participants | 127 Participants | 132 Participants | 128 Participants | 763 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 259 | 3 / 262 | 2 / 256 | 1 / 258 | 0 / 268 | 1 / 260 |
| other Total, other adverse events | 254 / 259 | 250 / 262 | 249 / 256 | 253 / 258 | 263 / 268 | 200 / 260 |
| serious Total, serious adverse events | 26 / 259 | 35 / 262 | 27 / 256 | 35 / 258 | 38 / 268 | 27 / 260 |
Outcome results
Primary
4-fold Rise in Anti-protective Antigen IgG Titer Response
Percent of participants who achieved a 4-fold or greater rise in anti-PA IgG Titer relative to the pre-vaccination level at month 0. The Dilutional Titer is the reciprocal of the dilution at which the anti-PA IgG response reaches a threshold. The lower limit of quantification (LLOQ) is 58, results below the LLOQ have been replaced by LLOQ (58) before calculating the fold response. Thus the lowest titer that can achieve 4-fold rise is 4\*58 = 232.
Time frame: 4 weeks after the m1, m6 and m42 injections
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SQ Females | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 43 | 100.0 % of participants with ≥4-fold rise |
| SQ Females | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 7 | 98.6 % of participants with ≥4-fold rise |
| SQ Females | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 2 | 94.9 % of participants with ≥4-fold rise |
| IM Female | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 43 | 100.0 % of participants with ≥4-fold rise |
| IM Female | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 7 | 98.6 % of participants with ≥4-fold rise |
| IM Female | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 2 | 91.9 % of participants with ≥4-fold rise |
| SQ Males | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 7 | NA % of participants with ≥4-fold rise |
| SQ Males | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 2 | NA % of participants with ≥4-fold rise |
| SQ Males | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 43 | 100.0 % of participants with ≥4-fold rise |
| IM Male | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 2 | NA % of participants with ≥4-fold rise |
| IM Male | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 43 | 99.3 % of participants with ≥4-fold rise |
| IM Male | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 7 | NA % of participants with ≥4-fold rise |
| Anthrax Vaccine Adsorbed 4-IM | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 2 | NA % of participants with ≥4-fold rise |
| Anthrax Vaccine Adsorbed 4-IM | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 43 | 99.4 % of participants with ≥4-fold rise |
| Anthrax Vaccine Adsorbed 4-IM | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 7 | NA % of participants with ≥4-fold rise |
| Anthrax Vaccine Adsorbed 754-IM | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 2 | 78.8 % of participants with ≥4-fold rise |
| Anthrax Vaccine Adsorbed 754-IM | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 7 | 97.8 % of participants with ≥4-fold rise |
| Anthrax Vaccine Adsorbed 754-IM | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 43 | NA % of participants with ≥4-fold rise |
| Saline Placebo IM or SQ | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 2 | 0.4 % of participants with ≥4-fold rise |
| Saline Placebo IM or SQ | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 43 | 0.0 % of participants with ≥4-fold rise |
| Saline Placebo IM or SQ | 4-fold Rise in Anti-protective Antigen IgG Titer Response | Month 7 | 0.5 % of participants with ≥4-fold rise |
Primary
Anti-protective Antigen IgG Geometric Mean Concentration
Geometric mean of the Anti-PA IgG Concentration measured in μg/mL. The lower limit of quantification (LLOQ) is 3.7, results below the LLOQ have been replaced by 1/2 LLOQ (1.85) before taking the geometric mean.
Time frame: 4 weeks after the m1, m6 and m42 injections
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SQ Females | Anti-protective Antigen IgG Geometric Mean Concentration | Month 2 | 94.3 μg/ml |
| SQ Females | Anti-protective Antigen IgG Geometric Mean Concentration | Month 7 | 201.1 μg/ml |
| SQ Females | Anti-protective Antigen IgG Geometric Mean Concentration | Month 43 | 216.8 μg/ml |
| IM Female | Anti-protective Antigen IgG Geometric Mean Concentration | Month 7 | 232.6 μg/ml |
| IM Female | Anti-protective Antigen IgG Geometric Mean Concentration | Month 43 | 320.5 μg/ml |
| IM Female | Anti-protective Antigen IgG Geometric Mean Concentration | Month 2 | 84.5 μg/ml |
| SQ Males | Anti-protective Antigen IgG Geometric Mean Concentration | Month 7 | NA μg/ml |
| SQ Males | Anti-protective Antigen IgG Geometric Mean Concentration | Month 43 | 254.8 μg/ml |
| SQ Males | Anti-protective Antigen IgG Geometric Mean Concentration | Month 2 | NA μg/ml |
| IM Male | Anti-protective Antigen IgG Geometric Mean Concentration | Month 7 | NA μg/ml |
| IM Male | Anti-protective Antigen IgG Geometric Mean Concentration | Month 43 | 310.0 μg/ml |
| IM Male | Anti-protective Antigen IgG Geometric Mean Concentration | Month 2 | NA μg/ml |
| Anthrax Vaccine Adsorbed 4-IM | Anti-protective Antigen IgG Geometric Mean Concentration | Month 7 | NA μg/ml |
| Anthrax Vaccine Adsorbed 4-IM | Anti-protective Antigen IgG Geometric Mean Concentration | Month 2 | NA μg/ml |
| Anthrax Vaccine Adsorbed 4-IM | Anti-protective Antigen IgG Geometric Mean Concentration | Month 43 | 433.2 μg/ml |
| Anthrax Vaccine Adsorbed 754-IM | Anti-protective Antigen IgG Geometric Mean Concentration | Month 43 | NA μg/ml |
| Anthrax Vaccine Adsorbed 754-IM | Anti-protective Antigen IgG Geometric Mean Concentration | Month 7 | 206.9 μg/ml |
| Anthrax Vaccine Adsorbed 754-IM | Anti-protective Antigen IgG Geometric Mean Concentration | Month 2 | 46.4 μg/ml |
| Saline Placebo IM or SQ | Anti-protective Antigen IgG Geometric Mean Concentration | Month 43 | 1.9 μg/ml |
| Saline Placebo IM or SQ | Anti-protective Antigen IgG Geometric Mean Concentration | Month 7 | 1.9 μg/ml |
| Saline Placebo IM or SQ | Anti-protective Antigen IgG Geometric Mean Concentration | Month 2 | 1.9 μg/ml |
Primary
Anti-protective Antigen IgG Geometric Mean Titer
Geometric mean of the Dilutional Titer. The Dilutional Titer is the reciprocal of the dilution at which the anti-PA IgG response reaches a threshold. The lower limit of quantification (LLOQ) is 58, results below the LLOQ have been replaced by 1/2 LLOQ (29) before taking the geometric mean.
Time frame: 4 weeks after the m1, m6 and m42 injections
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SQ Females | Anti-protective Antigen IgG Geometric Mean Titer | Month 7 | 2211.9 Dilutional Titer |
| SQ Females | Anti-protective Antigen IgG Geometric Mean Titer | Month 2 | 1048.5 Dilutional Titer |
| SQ Females | Anti-protective Antigen IgG Geometric Mean Titer | Month 43 | 2282.4 Dilutional Titer |
| IM Female | Anti-protective Antigen IgG Geometric Mean Titer | Month 7 | 2545.6 Dilutional Titer |
| IM Female | Anti-protective Antigen IgG Geometric Mean Titer | Month 2 | 934.8 Dilutional Titer |
| IM Female | Anti-protective Antigen IgG Geometric Mean Titer | Month 43 | 3425.4 Dilutional Titer |
| SQ Males | Anti-protective Antigen IgG Geometric Mean Titer | Month 43 | 2760.4 Dilutional Titer |
| SQ Males | Anti-protective Antigen IgG Geometric Mean Titer | Month 2 | NA Dilutional Titer |
| SQ Males | Anti-protective Antigen IgG Geometric Mean Titer | Month 7 | NA Dilutional Titer |
| IM Male | Anti-protective Antigen IgG Geometric Mean Titer | Month 43 | 3286.4 Dilutional Titer |
| IM Male | Anti-protective Antigen IgG Geometric Mean Titer | Month 2 | NA Dilutional Titer |
| IM Male | Anti-protective Antigen IgG Geometric Mean Titer | Month 7 | NA Dilutional Titer |
| Anthrax Vaccine Adsorbed 4-IM | Anti-protective Antigen IgG Geometric Mean Titer | Month 7 | NA Dilutional Titer |
| Anthrax Vaccine Adsorbed 4-IM | Anti-protective Antigen IgG Geometric Mean Titer | Month 2 | NA Dilutional Titer |
| Anthrax Vaccine Adsorbed 4-IM | Anti-protective Antigen IgG Geometric Mean Titer | Month 43 | 4683.8 Dilutional Titer |
| Anthrax Vaccine Adsorbed 754-IM | Anti-protective Antigen IgG Geometric Mean Titer | Month 43 | NA Dilutional Titer |
| Anthrax Vaccine Adsorbed 754-IM | Anti-protective Antigen IgG Geometric Mean Titer | Month 7 | 2257.0 Dilutional Titer |
| Anthrax Vaccine Adsorbed 754-IM | Anti-protective Antigen IgG Geometric Mean Titer | Month 2 | 514.6 Dilutional Titer |
| Saline Placebo IM or SQ | Anti-protective Antigen IgG Geometric Mean Titer | Month 2 | 29.7 Dilutional Titer |
| Saline Placebo IM or SQ | Anti-protective Antigen IgG Geometric Mean Titer | Month 43 | 29.0 Dilutional Titer |
| Saline Placebo IM or SQ | Anti-protective Antigen IgG Geometric Mean Titer | Month 7 | 29.7 Dilutional Titer |
Primary
Local AEs
warmth, tenderness, itching, pain, arm motion limitation, erythema, induration, nodule, and bruise. The number of injections analyzable varies for each event based on the presence or absence of reported data.
Time frame: 4 weeks after each injection
Population: There are missing data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SQ Females | Local AEs | Warmth | 500 injections |
| SQ Females | Local AEs | Erythema | 723 injections |
| SQ Females | Local AEs | Itching | 247 injections |
| SQ Females | Local AEs | Edema | 345 injections |
| SQ Females | Local AEs | Induration | 411 injections |
| SQ Females | Local AEs | Tenderness | 667 injections |
| SQ Females | Local AEs | Bruise | 69 injections |
| SQ Females | Local AEs | Arm Motion Limitation | 94 injections |
| SQ Females | Local AEs | Pain | 201 injections |
| SQ Females | Local AEs | Nodules | 409 injections |
| IM Female | Local AEs | Edema | 528 injections |
| IM Female | Local AEs | Warmth | 344 injections |
| IM Female | Local AEs | Pain | 569 injections |
| IM Female | Local AEs | Arm Motion Limitation | 434 injections |
| IM Female | Local AEs | Erythema | 952 injections |
| IM Female | Local AEs | Induration | 386 injections |
| IM Female | Local AEs | Nodules | 161 injections |
| IM Female | Local AEs | Bruise | 150 injections |
| IM Female | Local AEs | Tenderness | 1398 injections |
| IM Female | Local AEs | Itching | 160 injections |
| SQ Males | Local AEs | Nodules | 133 injections |
| SQ Males | Local AEs | Tenderness | 410 injections |
| SQ Males | Local AEs | Edema | 225 injections |
| SQ Males | Local AEs | Pain | 96 injections |
| SQ Males | Local AEs | Itching | 80 injections |
| SQ Males | Local AEs | Arm Motion Limitation | 50 injections |
| SQ Males | Local AEs | Warmth | 186 injections |
| SQ Males | Local AEs | Induration | 195 injections |
| SQ Males | Local AEs | Bruise | 65 injections |
| SQ Males | Local AEs | Erythema | 399 injections |
| IM Male | Local AEs | Bruise | 32 injections |
| IM Male | Local AEs | Edema | 354 injections |
| IM Male | Local AEs | Nodules | 98 injections |
| IM Male | Local AEs | Pain | 341 injections |
| IM Male | Local AEs | Itching | 77 injections |
| IM Male | Local AEs | Arm Motion Limitation | 218 injections |
| IM Male | Local AEs | Warmth | 189 injections |
| IM Male | Local AEs | Erythema | 603 injections |
| IM Male | Local AEs | Tenderness | 1075 injections |
| IM Male | Local AEs | Induration | 245 injections |
Primary
Systemic AEs
Fatigue, Muscle Ache, Headache, Fever, Tender Axillary Lymphnode The number of injections analyzable varies for each event based on the presence or absence of reported data.
Time frame: 4 weeks after each injection
Population: We analyzed by number of doses received. There might be missing data; people dropped out as time went on
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SQ Females | Systemic AEs | Fever | 0 injections |
| SQ Females | Systemic AEs | Muscle Ache | 57 injections |
| SQ Females | Systemic AEs | Tender Axillary Adenopathy | 10 injections |
| SQ Females | Systemic AEs | Headache | 90 injections |
| SQ Females | Systemic AEs | Fatigue | 118 injections |
| IM Female | Systemic AEs | Headache | 219 injections |
| IM Female | Systemic AEs | Fever | 0 injections |
| IM Female | Systemic AEs | Tender Axillary Adenopathy | 17 injections |
| IM Female | Systemic AEs | Muscle Ache | 226 injections |
| IM Female | Systemic AEs | Fatigue | 278 injections |
| SQ Males | Systemic AEs | Headache | 39 injections |
| SQ Males | Systemic AEs | Fatigue | 69 injections |
| SQ Males | Systemic AEs | Muscle Ache | 36 injections |
| SQ Males | Systemic AEs | Fever | 0 injections |
| SQ Males | Systemic AEs | Tender Axillary Adenopathy | 3 injections |
| IM Male | Systemic AEs | Fever | 1 injections |
| IM Male | Systemic AEs | Muscle Ache | 132 injections |
| IM Male | Systemic AEs | Fatigue | 182 injections |
| IM Male | Systemic AEs | Headache | 105 injections |
| IM Male | Systemic AEs | Tender Axillary Adenopathy | 8 injections |
Secondary
TNA ED50 Titer
Geometric mean of the ED50. The ED50 is the reciprocal of the dilution at which patient serum neutralizes 50% of a dose of anthrax lethal toxin (ED50). The lower limit of quantification (LLOQ) for this assay is 36, results below the LLOQ have been replaced with 1/2 LLOQ (18) before taking the geometric mean. Note that this secondary endpoint was only performed on \ 47% of the participants.
Time frame: 4 weeks after the m1, m6 and m42 injections
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SQ Females | TNA ED50 Titer | Month 43 | 1015.0 ED50 Dilutional Titer |
| SQ Females | TNA ED50 Titer | Month 7 | 1281.1 ED50 Dilutional Titer |
| SQ Females | TNA ED50 Titer | Month 2 | 229.1 ED50 Dilutional Titer |
| IM Female | TNA ED50 Titer | Month 43 | 1540.3 ED50 Dilutional Titer |
| IM Female | TNA ED50 Titer | Month 2 | 240.8 ED50 Dilutional Titer |
| IM Female | TNA ED50 Titer | Month 7 | 1630.0 ED50 Dilutional Titer |
| SQ Males | TNA ED50 Titer | Month 43 | 1451.0 ED50 Dilutional Titer |
| SQ Males | TNA ED50 Titer | Month 2 | NA ED50 Dilutional Titer |
| SQ Males | TNA ED50 Titer | Month 7 | NA ED50 Dilutional Titer |
| IM Male | TNA ED50 Titer | Month 2 | NA ED50 Dilutional Titer |
| IM Male | TNA ED50 Titer | Month 7 | NA ED50 Dilutional Titer |
| IM Male | TNA ED50 Titer | Month 43 | 1876.2 ED50 Dilutional Titer |
| Anthrax Vaccine Adsorbed 4-IM | TNA ED50 Titer | Month 2 | NA ED50 Dilutional Titer |
| Anthrax Vaccine Adsorbed 4-IM | TNA ED50 Titer | Month 43 | 2825.9 ED50 Dilutional Titer |
| Anthrax Vaccine Adsorbed 4-IM | TNA ED50 Titer | Month 7 | NA ED50 Dilutional Titer |
| Anthrax Vaccine Adsorbed 754-IM | TNA ED50 Titer | Month 7 | 1423.9 ED50 Dilutional Titer |
| Anthrax Vaccine Adsorbed 754-IM | TNA ED50 Titer | Month 43 | NA ED50 Dilutional Titer |
| Anthrax Vaccine Adsorbed 754-IM | TNA ED50 Titer | Month 2 | 165.5 ED50 Dilutional Titer |
| Saline Placebo IM or SQ | TNA ED50 Titer | Month 7 | 18.1 ED50 Dilutional Titer |
| Saline Placebo IM or SQ | TNA ED50 Titer | Month 43 | 18.0 ED50 Dilutional Titer |
| Saline Placebo IM or SQ | TNA ED50 Titer | Month 2 | 18.0 ED50 Dilutional Titer |