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| ID | Type | Description | Link |
|---|---|---|---|
| N01AI80006C |
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A Phase IV, randomized, multicenter trial to assess the immunogenicity and safety of BioThrax® in varying dose regimens with the primary objective of obtaining information on possible dose-sparing strategies in the event of a major biothreat.
This is a Phase IV, randomized, open-label immunogenicity and safety study to evaluate four dosing regimens of BioThrax® for Post-Exposure Prophylaxis (PEP) for anthrax. BioThrax® will be administered as a subcutaneous (SC) injection for the primary series and will be administered as an intramuscular (IM) injection for the boost. The four dosing regimens are: 0.50mL BioThrax® on Days 0, 14, and 6 month boost; 0.50mL BioThrax® on Days 0, 28 and 6 month boost; 0.50mL BioThrax® on Days 0, 14, 28 and 6 month boost and 0.25mL BioThrax® on Days 0, 14, and 28, 6 month boost with 0.50ml IM Approximately 300 subjects will be randomized 1:1:1:1 to one of the four study arms. Enrollment will be stratified by gender, with approximately equal numbers of males and females (18 through 65 years) enrolled into each dosing regimen. The Primary objective is to evaluate the immunogenicity of the four dosing regimens of BioThrax® using the Toxin Neutralization Assay (TNA). The secondary objective is to evaluate the safety of the four dosing regimens of BioThrax®.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm B: 0.50mL BioThrax® | Experimental | BioThrax® 0.50mL subcutaneously on Days 0, 28 and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects |
|
| Arm C: 0.50mL BioThrax® | Experimental | BioThrax® 0.50mL subcutaneously on Days 0, 14, 28 and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects |
|
| Arm D: 0.25mL BioThrax® | Experimental | BioThrax® 0.25mL subcutaneously on Days 0,14, and 28,and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects |
|
| Arm A: 0.50mL BioThrax® | Experimental | BioThrax® 0.50 ml subcutaneously on Days 0, 14, and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BioThrax® | Biological | BioThrax® is a sterile, milky white suspension made from cell free filtrates of microaerophilic cultures of an avirulent, nonencapsulated strain of Bacillus anthracis, will be administered as a 0.50mL IM injection 6 month boost for all groups |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With a Four-fold or Greater Increase From Baseline in Toxin Neutralization Antibody Assay (TNA) 50 Percent Neutralization Factor ( NF50 ) Antibody Titer | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the toxin neutralization antibody assay to determine the NF50 antibody titer. A participant met the threshold of a 4-fold rise in NF50 antibody titer if the post vaccination titer was an increase by 4-fold or more from the baseline (Day 0) titer. | Days 0, 7, 14, 21, 28 35, 42, 49, 56, 63, 70, 84 and 100 |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Concentration (GMC) of Enzyme-linked Immunosorbent Assay (ELISA) Antibody Against the Protective Antigen (Anti-PA IgG) | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the ELISA assay to determine the anti-PA IgG antibody concentration. The geometric mean of subjects' visit-specific titers were calculated along with the 95% confidence intervals. If the antibody titer was below the lower limit of quantification (LLOQ) for the assay, half the value of LLOQ (4.64) was imputed. When all subjects' titers were below LLOQ resulting in no variability within the group, the 95% CI was not calculated. |
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Inclusion Criteria:
Subject able to provide informed consent;
Female or male, 18 through 65 years of age, inclusive;
If the subject is female and of childbearing potential, she agrees to practice abstinence from sexual intercourse with men (vaginal penetration by a penis, coitus) or use acceptable contraception, initiated at least 30 days prior to the first study vaccination through 56 days after the 6 month boost vaccination in order to avoid pregnancy:
Be willing and able to return for all visits and blood collections for the duration of the study;
Be able to understand and comply with planned study procedures;
Agree to complete the memory aid and to report concomitant medications and Adverse Events during the study period.
Further clarification of inclusion/exclusion criteria:
Provided a subject meets all study inclusion criteria and none of the study exclusion criteria, the following conditions will not exclude the subject from study participation:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory Children's Center - Pediatric Infectious Diseases | Atlanta | Georgia | 30322-1014 | United States | ||
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Participants were healthy adult males and females recruited from existing volunteer populations and from the communities at large around the clinical sites. Participants were enrolled and vaccinated between 05JUL2012 and 30NOV2012.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: 0.50mL BioThrax, Days 0, 14 | BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost |
| FG001 | Arm B: 0.50mL BioThrax, Days 0, 28 | BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost |
| FG002 | Arm C: 0.50mL BioThrax, Days 0, 14, 28 | BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost |
| FG003 | Arm D: 0.25mL BioThrax, Days 0, 14, 28 | BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All participants are included in the baseline analysis population.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: 0.50mL BioThrax, Days 0, 14 | BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost |
| BG001 | Arm B: 0.50mL BioThrax, Days 0, 28 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With a Four-fold or Greater Increase From Baseline in Toxin Neutralization Antibody Assay (TNA) 50 Percent Neutralization Factor ( NF50 ) Antibody Titer | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the toxin neutralization antibody assay to determine the NF50 antibody titer. A participant met the threshold of a 4-fold rise in NF50 antibody titer if the post vaccination titer was an increase by 4-fold or more from the baseline (Day 0) titer. | The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all doses in the primary series, completed all scheduled visits up to and including the Day 100 visit in-window, and who contributed both pre- and post-vaccination blood samples for testing for which valid results were reported. | Posted | Number | participants | Days 0, 7, 14, 21, 28 35, 42, 49, 56, 63, 70, 84 and 100 |
|
Solicited events were collected for 8 days after each vaccination, unsolicited AEs through 28 days after last vaccination in the primary series and 21 days after the boost vaccination, and serious adverse events through 201 days after first vaccination.
For events solicited on a Memory Aid in the 8 days after vaccination, a participant was considered to have one event if it was reported as experienced at any time in the 8-day period. Each 8-day period was considered a separate event.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: 0.50mL BioThrax, Days 0, 14 | BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA (16.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Bernstein, MD, MA | Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center | 513-636-7625 | david.bernstein@cchmc.org |
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| ID | Term |
|---|---|
| D000881 | Anthrax |
| ID | Term |
|---|---|
| D016863 | Bacillaceae Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| ID | Term |
|---|---|
| C493276 | Biothrax |
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| BioThrax® | Biological | BioThrax® will be administered as: Arm A: 0.50mL SC injection on Days 0 and 14; Arm B: 0.50mL SC injection on Days 0 and 28; Arm C: 0.50mL SC injection on Days 0, 14 and 28; Arm D: 0.25 mL SC injection on Days 0, 14 and 28. |
|
| Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. |
| Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 0 by Maximum Severity | Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | Days 0-7 after vaccination at Day 0 |
| Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 14 by Maximum Severity | Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | Days 0-7 after vaccination at Day 14 |
| Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 28 by Maximum Severity | Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | Days 0-7 after vaccination at Day 28 |
| Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following the 6-month Boost by Maximum Severity | Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after the 6-month intramuscular boost vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | Days 0-7 after vaccination at Month 6 |
| Number of Participants With Injection Site Edema and Erythema With a Size of Greater Than 120 Millimeters (mm) | Participants were given a ruler with the memory aid to measure the occurrence of edema (swelling) and erythema (redness) daily for at least 8 days after each vaccination. Participants are counted in this outcome measure if they had measurements of greater than 120 mm in the 8-day period after at least one vaccination, first separately for edema and erythema, and in the last category, edema and/or erythema, if they had either or both reactions of greater than 120 mm. | Days 0-7 after each vaccination |
| TNA NF50 Geometric Mean Titers (GMT) at Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the toxin neutralization antibody assay to determine the NF50 antibody titer. The geometric mean of subjects' visit-specific titers were calculated along with the 95% confidence intervals. If the antibody titer was below the lower limit of quantification (LLOQ) for the assay, half the value of LLOQ (0.03) was imputed. When all subjects' titers were below LLOQ resulting in no variability within the group, the 95% CI was not calculated. | Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. |
| Peak Geometric Mean Concentration (GMC) of ELISA Anti-PA IgG Antibody Through Day 100 | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the ELISA assay to determine the anti-PA IgG antibody concentration. To determine the group peak GMC, the highest antibody concentration assessed for each subject at any post vaccination visit through Day 100 was determined. The geometric mean of subjects' peak concentrations was calculated along with the 95% confidence intervals. | Day 7 through Day 100 |
| Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 0 by Maximum Severity. | Participants maintained a memory aid to record daily the occurrence of solicited systemic reactions of fatigue, muscle aches, and headache for 8 days after vaccination based on their interference with daily activities. Severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | Days 0-7 after vaccination at Day 0 |
| Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 14 by Maximum Severity. | Participants maintained a memory aid to record daily the occurrence of solicited systemic reactions of fatigue, muscle aches, and headache for 8 days after vaccination based on their interference with daily activities. Severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | Days 0-7 after vaccination at Day 14 |
| Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 28 by Maximum Severity. | Participants maintained a memory aid to record daily the occurrence of solicited systemic reactions of fatigue, muscle aches, and headache for 8 days after vaccination based on their interference with daily activities. Severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | Days 0-7 after vaccination at Day 28 |
| Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After the 6-month Boost Vaccination by Maximum Severity. | Participants maintained a memory aid to record daily the occurrence of solicited systemic reactions of fatigue, muscle aches, and headache for 8 days after the 6-month intramuscular boost vaccination based on their interference with daily activities. Severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | Days 0-7 after vaccination at Month 6 |
| Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 0 by Maximum Severity | Participants were given a thermometer with a memory aid to record their oral temperature at least once daily, encouraged to be at the same time each day, but at any time the participant felt they may have a fever. The highest temperature assessed for each day was reported and graded according to the protocol grading scale of severe being greater than or equal to 39 degrees Celsius, moderate 38.5-38.9 degrees Celsius, and mild 38.0-38.4 degrees Celsius. Participants are counted by the maximum severity they reported experiencing fever on any of the 8 days. | Day 0-7 after vaccination at Day 0 |
| Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 14 by Maximum Severity | Participants were given a thermometer with a memory aid to record their oral temperature at least once daily, encouraged to be at the same time each day, but at any time the participant felt they may have a fever. The highest temperature assessed for each day was reported and graded according to the protocol grading scale of severe being greater than or equal to 39 degrees Celsius, moderate 38.5-38.9 degrees Celsius, and mild 38.0-38.4 degrees Celsius. Participants are counted by the maximum severity they reported experiencing fever on any of the 8 days. | Day 0-7 after vaccination at Day 14 |
| Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 28 by Maximum Severity | Participants were given a thermometer with a memory aid to record their oral temperature at least once daily, encouraged to be at the same time each day, but at any time the participant felt they may have a fever. The highest temperature assessed for each day was reported and graded according to the protocol grading scale of severe being greater than or equal to 39 degrees Celsius, moderate 38.5-38.9 degrees Celsius, and mild 38.0-38.4 degrees Celsius. Participants are counted by the maximum severity they reported experiencing fever on any of the 8 days. | Day 0-7 after vaccination at Day 28 |
| Number of Participants Reporting Fever in the Eight Days After the 6-month Boost Vaccination by Maximum Severity | Participants were given a thermometer with a memory aid to record their oral temperature at least once daily, encouraged to be at the same time each day, but at any time the participant felt they may have a fever. The highest temperature assessed for each day was reported and graded according to the protocol grading scale of severe being greater than or equal to 39 degrees Celsius, moderate 38.5-38.9 degrees Celsius, and mild 38.0-38.4 degrees Celsius. Participants are counted by the maximum severity they reported experiencing fever on any of the 8 days. | Day 0-7 after vaccination at Month 6 |
| Number of Subjects With a Four-fold or Greater Increase From Baseline in Enzyme-linked Immunosorbent Assay (ELISA) Antibody Concentration Against the Protective Antigen (Anti-PA IgG) | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the ELISA assay to determine the anti-PA IgG antibody concentration. A participant met the threshold of a 4-fold rise in anti-PA IgG antibody concentration if the post vaccination concentration was an increase by 4-fold or more from the baseline (Day 0) concentration. | Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. |
| TNA NF50 Peak Geometric Mean Titer (GMT) Antibody Response Through Day 100 | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the toxin neutralization antibody assay to determine the NF50 antibody titer. To determine the group peak GMT, the highest titer assessed for each subject at any post vaccination visit through Day 100 was determined. The geometric mean of each subjects' peak titers was calculated along with the 95% confidence intervals. | Day 7 through Day 100 |
| Cincinnati Children's Hospital Medical Center - Infectious Diseases |
| Cincinnati |
| Ohio |
| 45229-3026 |
| United States |
| Baylor College of Medicine - Molecular Virology and Microbiology | Houston | Texas | 77030-3411 | United States |
| Group Health Research Institute - Seattle | Seattle | Washington | 98101-1466 | United States |
| Withdrawal by Subject |
|
| Adverse Event |
|
| Lost to Follow-up |
|
| Protocol Violation |
|
| Pregnancy |
|
| no longer eligible |
|
BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
| BG002 | Arm C: 0.50mL BioThrax, Days 0, 14, 28 | BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost |
| BG003 | Arm D: 0.25mL BioThrax, Days 0, 14, 28 | BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Arm A: 0.50mL BioThrax, Days 0, 14 |
BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost |
| OG001 | Arm B: 0.50mL BioThrax, Days 0, 28 | BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost |
| OG002 | Arm C: 0.50mL BioThrax, Days 0, 14, 28 | BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost |
| OG003 | Arm D: 0.25mL BioThrax, Days 0, 14, 28 | BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost |
|
|
| Secondary | Geometric Mean Concentration (GMC) of Enzyme-linked Immunosorbent Assay (ELISA) Antibody Against the Protective Antigen (Anti-PA IgG) | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the ELISA assay to determine the anti-PA IgG antibody concentration. The geometric mean of subjects' visit-specific titers were calculated along with the 95% confidence intervals. If the antibody titer was below the lower limit of quantification (LLOQ) for the assay, half the value of LLOQ (4.64) was imputed. When all subjects' titers were below LLOQ resulting in no variability within the group, the 95% CI was not calculated. | The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all doses in the primary series, completed all scheduled visits up to and including the Day 100 visit in-window, and who contributed both pre- and post-vaccination blood samples for testing for which valid results were reported. | Posted | Geometric Mean | 95% Confidence Interval | µg/mL | Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. |
|
|
|
| Secondary | Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 0 by Maximum Severity | Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | The analysis population includes all participants who were vaccinated at Day 0 per protocol, excluding 59 participants at one clinic site who were vaccinated in the fatty tissue over the triceps rather than the intended inferior deltoid. | Posted | Number | participants | Days 0-7 after vaccination at Day 0 |
|
|
|
| Secondary | Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 14 by Maximum Severity | Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | The analysis population includes all participants who were vaccinated at Day 14 per protocol, excluding 59 participants at one clinic site who were vaccinated in the fatty tissue over the triceps rather than the intended inferior deltoid. | Posted | Number | participants | Days 0-7 after vaccination at Day 14 |
|
|
|
| Secondary | Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 28 by Maximum Severity | Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | The analysis population includes all participants who were vaccinated at Day 28 per protocol, excluding 59 participants at one clinic site who were vaccinated in the fatty tissue over the triceps rather than the intended inferior deltoid. | Posted | Number | participants | Days 0-7 after vaccination at Day 28 |
|
|
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| Secondary | Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following the 6-month Boost by Maximum Severity | Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after the 6-month intramuscular boost vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | The analysis population includes all participants who received the 6-month booster vaccination. | Posted | Number | participants | Days 0-7 after vaccination at Month 6 |
|
|
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| Secondary | Number of Participants With Injection Site Edema and Erythema With a Size of Greater Than 120 Millimeters (mm) | Participants were given a ruler with the memory aid to measure the occurrence of edema (swelling) and erythema (redness) daily for at least 8 days after each vaccination. Participants are counted in this outcome measure if they had measurements of greater than 120 mm in the 8-day period after at least one vaccination, first separately for edema and erythema, and in the last category, edema and/or erythema, if they had either or both reactions of greater than 120 mm. | The analysis population includes all participants who were vaccinated per protocol, excluding 59 participants at one clinic site who were vaccinated in the fatty tissue over the triceps rather than the intended inferior deltoid. | Posted | Number | participants | Days 0-7 after each vaccination |
|
|
|
| Secondary | TNA NF50 Geometric Mean Titers (GMT) at Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the toxin neutralization antibody assay to determine the NF50 antibody titer. The geometric mean of subjects' visit-specific titers were calculated along with the 95% confidence intervals. If the antibody titer was below the lower limit of quantification (LLOQ) for the assay, half the value of LLOQ (0.03) was imputed. When all subjects' titers were below LLOQ resulting in no variability within the group, the 95% CI was not calculated. | The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all doses in the primary series, completed all scheduled visits up to and including the Day 100 visit in-window, and who contributed both pre- and post-vaccination blood samples for testing for which valid results were reported. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. |
|
|
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| Secondary | Peak Geometric Mean Concentration (GMC) of ELISA Anti-PA IgG Antibody Through Day 100 | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the ELISA assay to determine the anti-PA IgG antibody concentration. To determine the group peak GMC, the highest antibody concentration assessed for each subject at any post vaccination visit through Day 100 was determined. The geometric mean of subjects' peak concentrations was calculated along with the 95% confidence intervals. | The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all doses in the primary series, completed all scheduled visits up to and including the Day 100 visit in-window, and who contributed both pre- and post-vaccination blood samples for testing for which valid results were reported. | Posted | Geometric Mean | 95% Confidence Interval | µg/mL | Day 7 through Day 100 |
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|
| Secondary | Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 0 by Maximum Severity. | Participants maintained a memory aid to record daily the occurrence of solicited systemic reactions of fatigue, muscle aches, and headache for 8 days after vaccination based on their interference with daily activities. Severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | The analysis population includes all participants who were vaccinated at Day 0 per protocol, excluding 59 participants at one clinic site who were vaccinated in the fatty tissue over the triceps rather than the intended inferior deltoid. | Posted | Number | participants | Days 0-7 after vaccination at Day 0 |
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|
|
| Secondary | Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 14 by Maximum Severity. | Participants maintained a memory aid to record daily the occurrence of solicited systemic reactions of fatigue, muscle aches, and headache for 8 days after vaccination based on their interference with daily activities. Severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | The analysis population includes all participants who were vaccinated at Day 14 per protocol, excluding 59 participants at one clinic site who were vaccinated in the fatty tissue over the triceps rather than the intended inferior deltoid. | Posted | Number | participants | Days 0-7 after vaccination at Day 14 |
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|
|
| Secondary | Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 28 by Maximum Severity. | Participants maintained a memory aid to record daily the occurrence of solicited systemic reactions of fatigue, muscle aches, and headache for 8 days after vaccination based on their interference with daily activities. Severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | The analysis population includes all participants who were vaccinated at Day 28 per protocol, excluding 59 participants at one clinic site who were vaccinated in the fatty tissue over the triceps rather than the intended inferior deltoid. | Posted | Number | participants | Days 0-7 after vaccination at Day 28 |
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|
|
| Secondary | Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After the 6-month Boost Vaccination by Maximum Severity. | Participants maintained a memory aid to record daily the occurrence of solicited systemic reactions of fatigue, muscle aches, and headache for 8 days after the 6-month intramuscular boost vaccination based on their interference with daily activities. Severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days. | The analysis population includes all participants who received the 6-month boost vaccination. | Posted | Number | participants | Days 0-7 after vaccination at Month 6 |
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|
| Secondary | Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 0 by Maximum Severity | Participants were given a thermometer with a memory aid to record their oral temperature at least once daily, encouraged to be at the same time each day, but at any time the participant felt they may have a fever. The highest temperature assessed for each day was reported and graded according to the protocol grading scale of severe being greater than or equal to 39 degrees Celsius, moderate 38.5-38.9 degrees Celsius, and mild 38.0-38.4 degrees Celsius. Participants are counted by the maximum severity they reported experiencing fever on any of the 8 days. | The analysis population includes all participants who were vaccinated at Day 0 per protocol, excluding 59 participants at one clinic site who were vaccinated in the fatty tissue over the triceps rather than the intended inferior deltoid. | Posted | Number | participants | Day 0-7 after vaccination at Day 0 |
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|
| Secondary | Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 14 by Maximum Severity | Participants were given a thermometer with a memory aid to record their oral temperature at least once daily, encouraged to be at the same time each day, but at any time the participant felt they may have a fever. The highest temperature assessed for each day was reported and graded according to the protocol grading scale of severe being greater than or equal to 39 degrees Celsius, moderate 38.5-38.9 degrees Celsius, and mild 38.0-38.4 degrees Celsius. Participants are counted by the maximum severity they reported experiencing fever on any of the 8 days. | The analysis population includes all participants who were vaccinated at Day 14 per protocol, excluding 59 participants at one clinic site who were vaccinated in the fatty tissue over the triceps rather than the intended inferior deltoid. | Posted | Number | participants | Day 0-7 after vaccination at Day 14 |
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|
|
| Secondary | Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 28 by Maximum Severity | Participants were given a thermometer with a memory aid to record their oral temperature at least once daily, encouraged to be at the same time each day, but at any time the participant felt they may have a fever. The highest temperature assessed for each day was reported and graded according to the protocol grading scale of severe being greater than or equal to 39 degrees Celsius, moderate 38.5-38.9 degrees Celsius, and mild 38.0-38.4 degrees Celsius. Participants are counted by the maximum severity they reported experiencing fever on any of the 8 days. | The analysis population includes all participants who were vaccinated at Day 28 per protocol, excluding 59 participants at one clinic site who were vaccinated in the fatty tissue over the triceps rather than the intended inferior deltoid. | Posted | Number | participants | Day 0-7 after vaccination at Day 28 |
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|
| Secondary | Number of Participants Reporting Fever in the Eight Days After the 6-month Boost Vaccination by Maximum Severity | Participants were given a thermometer with a memory aid to record their oral temperature at least once daily, encouraged to be at the same time each day, but at any time the participant felt they may have a fever. The highest temperature assessed for each day was reported and graded according to the protocol grading scale of severe being greater than or equal to 39 degrees Celsius, moderate 38.5-38.9 degrees Celsius, and mild 38.0-38.4 degrees Celsius. Participants are counted by the maximum severity they reported experiencing fever on any of the 8 days. | The analysis population includes all participants who received the 6-month boost vaccination and recorded oral temperatures. | Posted | Number | participants | Day 0-7 after vaccination at Month 6 |
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| Secondary | Number of Subjects With a Four-fold or Greater Increase From Baseline in Enzyme-linked Immunosorbent Assay (ELISA) Antibody Concentration Against the Protective Antigen (Anti-PA IgG) | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the ELISA assay to determine the anti-PA IgG antibody concentration. A participant met the threshold of a 4-fold rise in anti-PA IgG antibody concentration if the post vaccination concentration was an increase by 4-fold or more from the baseline (Day 0) concentration. | The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all doses in the primary series, completed all scheduled visits up to and including the Day 100 visit in-window, and who contributed both pre- and post-vaccination blood samples for testing for which valid results were reported. | Posted | Number | participants | Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. |
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| Secondary | TNA NF50 Peak Geometric Mean Titer (GMT) Antibody Response Through Day 100 | Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the toxin neutralization antibody assay to determine the NF50 antibody titer. To determine the group peak GMT, the highest titer assessed for each subject at any post vaccination visit through Day 100 was determined. The geometric mean of each subjects' peak titers was calculated along with the 95% confidence intervals. | The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all doses in the primary series, completed all scheduled visits up to and including the Day 100 visit in-window, and who contributed both pre- and post-vaccination blood samples for testing for which valid results were reported. | Posted | Geometric Mean | 95% Confidence Interval | titer | Day 7 through Day 100 |
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|
|
| 0 |
| 82 |
| 82 |
| 82 |
| EG001 | Arm B: 0.50mL BioThrax, Days 0, 28 | BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost | 2 | 82 | 82 | 82 |
| EG002 | Arm C: 0.50mL BioThrax, Days 0, 14, 28 | BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost | 1 | 82 | 82 | 82 |
| EG003 | Arm D: 0.25mL BioThrax, Days 0, 14, 28 | BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost | 0 | 82 | 82 | 82 |
| Localised infection | Infections and infestations | MedDRA (16.1) | Non-systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA (16.1) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment | Solicited as 'muscle aches' on the memory aid |
|
| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Vaccination site pain | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Vaccination site pruritus | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Vaccination site warmth | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Tenderness | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment | Solicited as "arm motion limitations" on the memory aid |
|
| Vaccination site erythema | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Vaccination site swelling | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA (16.1) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (16.1) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (16.1) | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (16.1) | Non-systematic Assessment |
|
| Respiratory rate increased | Investigations | MedDRA (16.1) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (16.1) | Non-systematic Assessment |
|
| Vaccination site bruising | General disorders | MedDRA (16.1) | Non-systematic Assessment |
|
| Vaccination site erythema | General disorders | MedDRA (16.1) | Non-systematic Assessment | Vaccination site erythema that persisted beyond 14 days post vaccination was reported as an unsolicited adverse event. |
|
| Vaccination site nodule | General disorders | MedDRA (16.1) | Non-systematic Assessment |
|
| Vessel puncture site bruise | General disorders | MedDRA (16.1) | Non-systematic Assessment |
|
Not provided
| D007239 | Infections |
| Day 7 |
|
| Day 14 |
|
| Day 21 |
|
| Day 28 |
|
| Day 35 |
|
| Day 42 |
|
| Day 49 |
|
| Day 56 |
|
| Day 63 |
|
| Day 70 |
|
| Day 84 |
|
| Day 100 |
|
| Pain at injection site, moderate |
|
| Pain at injection site, mild |
|
| Itchiness at injection site, severe |
|
| Itchiness at injection site, moderate |
|
| Itchiness at injection site, mild |
|
| Warmth at injection site, severe |
|
| Warmth at injection site, moderate |
|
| Warmth at injection site, mild |
|
| Tenderness at injection site, severe |
|
| Tenderness at injection site, moderate |
|
| Tenderness at injection site, mild |
|
| Arm motion limitations, severe |
|
| Arm motion limitations, moderate |
|
| Arm motion limitations, mild |
|
| Erythema, severe |
|
| Erythema, moderate |
|
| Erythema, mild |
|
| Edema, severe |
|
| Edema, moderate |
|
| Edema, mild |
|
|
| Pain at injection site, mild |
|
| Itchiness at injection site, severe |
|
| Itchiness at injection site, moderate |
|
| Itchiness at injection site, mild |
|
| Warmth at injection site, severe |
|
| Warmth at injection site, moderate |
|
| Warmth at injection site, mild |
|
| Tenderness at injection site, severe |
|
| Tenderness at injection site, moderate |
|
| Tenderness at injection site, mild |
|
| Arm motion limitations, severe |
|
| Arm motion limitations, moderate |
|
| Arm motion limitations, mild |
|
| Erythema, severe |
|
| Erythema, moderate |
|
| Erythema, mild |
|
| Edema, severe |
|
| Edema, moderate |
|
| Edema, mild |
|
|
| Pain at injection site, mild |
|
| Itchiness at injection site, severe |
|
| Itchiness at injection site, moderate |
|
| Itchiness at injection site, mild |
|
| Warmth at injection site, severe |
|
| Warmth at injection site, moderate |
|
| Warmth at injection site, mild |
|
| Tenderness at injection site, severe |
|
| Tenderness at injection site, moderate |
|
| Tenderness at injection site, mild |
|
| Arm motion limitations, severe |
|
| Arm motion limitations, moderate |
|
| Arm motion limitations, mild |
|
| Erythema, severe |
|
| Erythema, moderate |
|
| Erythema, mild |
|
| Edema, severe |
|
| Edema, moderate |
|
| Edema, mild |
|
| Pain at injection site, moderate |
|
| Pain at injection site, mild |
|
| Itchiness at injection site, severe |
|
| Itchiness at injection site, moderate |
|
| Itchiness at injection site, mild |
|
| Warmth at injection site, severe |
|
| Warmth at injection site, moderate |
|
| Warmth at injection site, mild |
|
| Tenderness at injection site, severe |
|
| Tenderness at injection site, moderate |
|
| Tenderness at injection site, mild |
|
| Arm motion limitations, severe |
|
| Arm motion limitations, moderate |
|
| Arm motion limitations, mild |
|
| Erythema, severe |
|
| Erythema, moderate |
|
| Erythema, mild |
|
| Edema, severe |
|
| Edema, moderate |
|
| Edema, mild |
|
| Erythema |
|
| Edema and/or Erythema |
|
| Day 7 |
|
| Day 14 |
|
| Day 21 |
|
| Day 28 |
|
| Day 35 |
|
| Day 42 |
|
| Day 49 |
|
| Day 56 |
|
| Day 63 |
|
| Day 70 |
|
| Day 84 |
|
| Day 100 |
|
| Fatigue, moderate |
|
| Fatigue, mild |
|
| Muscle aches, severe |
|
| Muscle aches, moderate |
|
| Muscle aches, mild |
|
| Headache, severe |
|
| Headache, moderate |
|
| Headache, mild |
|
| Title | Measurements |
|---|---|
|
| Fatigue, mild |
|
| Muscle aches, severe |
|
| Muscle aches, moderate |
|
| Muscle aches, mild |
|
| Headache, severe |
|
| Headache, moderate |
|
| Headache, mild |
|
| Title | Measurements |
|---|---|
|
| Fatigue, mild |
|
| Muscle aches, severe |
|
| Muscle aches, moderate |
|
| Muscle aches, mild |
|
| Headache, severe |
|
| Headache, moderate |
|
| Headache, mild |
|
| Fatigue, moderate |
|
| Fatigue, mild |
|
| Muscle aches, severe |
|
| Muscle aches, moderate |
|
| Muscle aches, mild |
|
| Headache, severe |
|
| Headache, moderate |
|
| Headache, mild |
|
| Fever, moderate |
|
| Fever, mild |
|
| Title | Measurements |
|---|---|
|
| Fever, mild |
|
| Title | Measurements |
|---|---|
|
| Fever, mild |
|
| Fever, moderate |
|
| Fever, mild |
|
| Day 14 |
|
| Day 21 |
|
| Day 28 |
|
| Day 35 |
|
| Day 42 |
|
| Day 49 |
|
| Day 56 |
|
| Day 63 |
|
| Day 70 |
|
| Day 84 |
|
| Day 100 |
|