Assessment of the Immunogenicity and Safety of a Dose-Sparing BioThrax® AVA Schedule

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01641991
• Collaborator: (none)
• Enrollment: 328
• Locations: 4
• Arms: 4
• Duration (Months): 11
• Patients Per Site: 82
• Patients Per Site Per Month: 7.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Bacillus Anthracis (Anthrax)	Biological: BioThrax®; Biological: BioThrax®	Phase 4

Detailed Description

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®.

Study Design

• Study Type: Interventional
• Actual Enrollment: 328 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Randomized Trial for the Assessment of Immunogenicity and Safety of Four Different Dosing Regimens of BioThrax® for Post-Exposure Prophylaxis for Anthrax in Adults
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm B: 0.50mL BioThrax® BioThrax® 0.50mL subcutaneously on Days 0, 28 and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects	Biological: BioThrax®; 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; Biological: BioThrax®; 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.
Experimental: Arm C: 0.50mL BioThrax® BioThrax® 0.50mL subcutaneously on Days 0, 14, 28 and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects	Biological: BioThrax®; 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; Biological: BioThrax®; 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.
Experimental: Arm D: 0.25mL BioThrax® BioThrax® 0.25mL subcutaneously on Days 0,14, and 28,and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects	Biological: BioThrax®; 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; Biological: BioThrax®; 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.
Experimental: Arm A: 0.50mL BioThrax® BioThrax® 0.50 ml subcutaneously on Days 0, 14, and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects	Biological: BioThrax®; 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; Biological: BioThrax®; 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.

Outcome Measures

Primary Outcome Measures

1. 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 [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. 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.

Secondary Outcome Measures

1. Geometric Mean Concentration (GMC) of Enzyme-linked Immunosorbent Assay (ELISA) Antibody Against the Protective Antigen (Anti-PA IgG) [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 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.

2. Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 0 by Maximum Severity [Days 0-7 after vaccination at Day 0]

   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.

3. Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 14 by Maximum Severity [Days 0-7 after vaccination at Day 14]

   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.

4. Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 28 by Maximum Severity [Days 0-7 after vaccination at Day 28]

   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.

5. Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following the 6-month Boost by Maximum Severity [Days 0-7 after vaccination at Month 6]

   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.

6. Number of Participants With Injection Site Edema and Erythema With a Size of Greater Than 120 Millimeters (mm) [Days 0-7 after each vaccination]

   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.

7. TNA NF50 Geometric Mean Titers (GMT) at Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. [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.

8. Peak Geometric Mean Concentration (GMC) of ELISA Anti-PA IgG Antibody Through Day 100 [Day 7 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.

9. Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 0 by Maximum Severity. [Days 0-7 after vaccination at Day 0]

   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.

10. Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 14 by Maximum Severity. [Days 0-7 after vaccination at Day 14]

    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.

11. Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 28 by Maximum Severity. [Days 0-7 after vaccination at Day 28]

    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.

12. Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After the 6-month Boost Vaccination by Maximum Severity. [Days 0-7 after vaccination at Month 6]

    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.

13. Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 0 by Maximum Severity [Day 0-7 after vaccination at Day 0]

    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.

14. Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 14 by Maximum Severity [Day 0-7 after vaccination at Day 14]

    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.

15. Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 28 by Maximum Severity [Day 0-7 after vaccination at Day 28]

    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.

16. Number of Participants Reporting Fever in the Eight Days After the 6-month Boost Vaccination by Maximum Severity [Day 0-7 after vaccination at Month 6]

    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.

17. 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) [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 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.

18. TNA NF50 Peak Geometric Mean Titer (GMT) Antibody Response Through Day 100 [Day 7 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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:

1. A woman is considered of childbearing potential unless post-menopausal (>/= 1 year without menses) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy)

2. Acceptable contraception methods are restricted to effective devices (IUDs, NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, condoms with spermicidal agents, monogamous relationship with a vasectomized partner who has been vasectomized for 6 months or more prior to study entry, or successful Essure placement with documented confirmation test at least 3 months after the procedure, and any other Food and Drug Administration (FDA)-approved contraceptive method

• 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:

• History of gestational diabetes;

• Type II diabetes controlled with diet or oral hypoglycemic medications;

• Treated, controlled, uncomplicated hypertension;

• History of coronary artery disease, asymptomatic (New York Heart Association [NYHA] Function Class I), on a stable medical regimen. Persons meeting these criteria must be at least two years post-myocardial infarction, cardiac bypass surgery and/or percutaneous coronary interventions (e.g., angioplasty, stent placement) in order to qualify. Persons with a history of cardiac disease must be under the care of a physician;

• Cured, non-metastatic cancer (excluding hematologic malignancies), disease-free for five years;

• Localized skin cancer, resected (including squamous cell and basal cell carcinomas). Participants with a history of melanoma must be disease-free for five years;

• Exercise-induced bronchospasm controlled with inhaled medication(s) only;

• Mild asthma: Subjects who have not been hospitalized for asthma in the past two years and use only inhalers to control their symptoms will be eligible. Only low to medium doses of inhaled steroids, defined as </=3 puffs a day, are allowed. Persons who require oral or parenteral steroids will not be eligible.

• Subjects with isolated entrapment neuropathies, such as carpal tunnel syndrome, or compression neuropathies, such as lumbar radiculopathy, that are not associated with systemic disease or immune dysfunction may be eligible for enrollment. If the subject's condition has been stable for six months, surgery is not planned for the condition, the neurologic examination is normal (specifically no weakness or paresthesias), and the mononeuropathy will not interfere with the assessment of reactogenicity, the subject is eligible.

• Subjects with vitiligo who are otherwise healthy and the vitiligo is not widespread in the area of the vaccinations may be eligible for enrollment.

• Subjects with seasonal allergies are eligible provided the dose of nasal steroids that are used is < 800µg/day.

Exclusion Criteria:

• Have a prior history of anthrax or immunization against anthrax;

• Intend to enlist in the military during the study;

• Have a known allergy to aluminum hydroxide, formaldehyde, benzethonium chloride, or latex;

• (Females only) Be pregnant, plan to become pregnant at any time between the Screening Visit through 56 days after the 6 month boost vaccination, or refuse to use/not have used an acceptable method of birth control (see Inclusion Criterion 3) from 30 days prior to the first study vaccine dose through 56 days after the 6 month boost vaccination;

• Have received experimental products within 30 days before study entry or plan to receive experimental products at any time during the study;

• Have received a live vaccine within 30 days before study entry or plan to receive a live vaccine prior to Day 63 of the study or within 30 days of the 6 month boost;

• Have received an inactivated vaccine within 14 days before study entry or plan to receive an inactivated vaccine from Day 0 to Day 42 or within 14 days of the 6 month boost;

• Have received immunosuppressive therapy (including systemic steroids) within 3 months prior to study entry or plan to receive immunosuppressive therapy at any time during the study;

• Have received cytotoxic therapy in the previous 5 years or plan to receive cytotoxic therapy at any time during the study;

• Have received parenteral immunoglobulin or blood products within 3 months of the study or plan to receive parenteral immunoglobulin or blood products at any time during the study;

• Have a history of Guillain-Barré Syndrome;

• Have an active malignancy or history of metastatic or hematologic malignancy;

• Have Type I diabetes or Type II diabetes treated with insulin;

• Have cardiovascular disease (including any person with a history of cardiomyopathy or congestive heart failure);

• Have moderate to severe asthma, chronic obstructive pulmonary disease or other significant pulmonary disease;

• Have hepatic or renal insufficiency;

• Have an autoimmune, inflammatory, vasculitic or rheumatic disease including but not limited to systemic lupus erythematosus, polymyalgia rheumatica, rheumatoid arthritis or scleroderma;

• Have HIV, hepatitis B or hepatitis C infection;

• Have any other condition known to produce or be associated with immunosuppression;

• Have neuropathy or any other evolving neurological condition;

• Have an ongoing drug abuse/dependence (including alcohol) issues or a history of these issues within five years of enrollment;

• Have a seizure disorder;

• Have moderate or severe illness and/or an oral temperature >100.4 F within 3 days prior to vaccination;

• Have a blood pressure, heart rate or respiratory rate of Grade 2 or higher;

• Have any chronic condition that, in the opinion of the Investigator, would render vaccination unsafe or would interfere with study evaluations or completion of the study;

• Have a total White Blood Cell (WBC) count, Absolute Neutrophil Count (ANC), hemoglobin or platelet count that is Grade 2 or higher;

• Have a creatinine higher than the normal range;

• Have an Alanine Aminotransferase (ALT) of >/= 1.2 x Upper Limit of Normal;

• Have a value higher than trace for glucose and/or protein on urinalysis;

• Have a history of hospitalization for psychiatric illness, suicide attempt, or confinement for danger to self or others, within the past 10 years. (Subjects with a psychiatric disorder [not meeting exclusion criteria, e.g. attention-deficit hyperactivity disorder] that is controlled for a minimum of 3 months and the investigator has determined that the subject's mental status will not compromise the subject's ability to comply with protocol requirements may be enrolled);

• Be taking any of the following psychiatric drugs: aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, trifluopromazine, chlorprothixene, chlorpromazine, perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate;

• Be taking more than one antidepressant drug not included in the list above (subjects taking only one antidepressant drug [not listed in excluded psychiatric drugs] who are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study provided the investigator determines the subject's mental status will not compromise the subject's ability to comply with protocol requirements);

• Have donated blood within 30 days of enrollment or plans to donate blood during the study.

• Have a tattoo in the area of the vaccination sites which will interfere with the assessment of injection site reactogenicity.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory Children's Center - Pediatric Infectious Diseases	Atlanta	Georgia	United States	30322-1014
2	Cincinnati Children's Hospital Medical Center - Infectious Diseases	Cincinnati	Ohio	United States	45229-3026
3	Baylor College of Medicine - Molecular Virology and Microbiology	Houston	Texas	United States	77030-3411
4	Group Health Research Institute - Seattle	Seattle	Washington	United States	98101-1466

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01641991
• Other Study ID Numbers: 11-0024; N01AI80006C
• First Posted: Jul 17, 2012
• Last Update Posted: May 28, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Bacillus anthracis, anthrax, vaccine, BioThrax®, dose-sparing
• Additional relevant MeSH terms: Anthrax

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Period Title: Overall Study
STARTED	82	82	82	82
COMPLETED	73	74	65	66
NOT COMPLETED	9	8	17	16

Baseline Characteristics

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28	Total
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	Total of all reporting groups
Overall Participants	82	82	82	82	328
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.0 (10.8)	36.7 (11.7)	34.6 (11.5)	36.5 (11.1)	35.7 (11.2)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	82 100%	82 100%	82 100%	82 100%	328 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	43 52.4%	42 51.2%	40 48.8%	41 50%	166 50.6%
Male	39 47.6%	40 48.8%	42 51.2%	41 50%	162 49.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	2 2.4%	3 3.7%	1 1.2%	3 3.7%	9 2.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	7 8.5%	14 17.1%	19 23.2%	15 18.3%	55 16.8%
White	67 81.7%	61 74.4%	56 68.3%	61 74.4%	245 74.7%
More than one race	6 7.3%	3 3.7%	5 6.1%	2 2.4%	16 4.9%
Unknown or Not Reported	0 0%	1 1.2%	1 1.2%	1 1.2%	3 0.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 7.3%	4 4.9%	3 3.7%	6 7.3%	19 5.8%
Not Hispanic or Latino	76 92.7%	78 95.1%	79 96.3%	76 92.7%	309 94.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	82 100%	82 100%	82 100%	82 100%	328 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	Days 0, 7, 14, 21, 28 35, 42, 49, 56, 63, 70, 84 and 100

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	67	59	59	60
Day 7	1 1.2%	0 0%	1 1.2%	0 0%
Day 14	4 4.9%	1 1.2%	1 1.2%	0 0%
Day 21	26 31.7%	12 14.6%	19 23.2%	12 14.6%
Day 28	63 76.8%	13 15.9%	56 68.3%	46 56.1%
Day 35	65 79.3%	32 39%	59 72%	53 64.6%
Day 42	63 76.8%	59 72%	59 72%	58 70.7%
Day 49	63 76.8%	59 72%	59 72%	56 68.3%
Day 56	59 72%	59 72%	59 72%	55 67.1%
Day 63	57 69.5%	59 72%	59 72%	54 65.9%
Day 70	56 68.3%	59 72%	59 72%	54 65.9%
Day 84	44 53.7%	58 70.7%	58 70.7%	51 62.2%
Day 100	34 41.5%	54 65.9%	56 68.3%	44 53.7%

2. Secondary Outcome

Title	Geometric Mean Concentration (GMC) of Enzyme-linked Immunosorbent Assay (ELISA) Antibody Against the Protective Antigen (Anti-PA IgG)
Description	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.
Time Frame	Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	67	59	59	60
Day 0	4.64	4.64	4.64	4.64
Day 7	5.01	4.71	4.91	4.70
Day 14	6.16	5.48	5.28	5.01
Day 21	13.67	7.62	12.11	7.63
Day 28	88.43	7.62	84.05	52.13
Day 35	89.44	17.16	154.49	86.74
Day 42	76.32	253.53	170.40	108.26
Day 49	61.77	201.87	141.93	93.07
Day 56	52.95	158.13	119.28	77.77
Day 63	41.87	128.92	99.20	66.54
Day 70	36.32	105.14	87.13	56.48
Day 84	25.75	70.14	65.42	43.30
Day 100	19.38	51.22	48.77	32.53

3. Secondary Outcome

Title	Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 0 by Maximum Severity
Description	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.
Time Frame	Days 0-7 after vaccination at Day 0

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	67	67	68	67
Pain at injection site, severe	0 0%	0 0%	0 0%	0 0%
Pain at injection site, moderate	17 20.7%	12 14.6%	12 14.6%	8 9.8%
Pain at injection site, mild	29 35.4%	41 50%	42 51.2%	35 42.7%
Itchiness at injection site, severe	0 0%	0 0%	0 0%	0 0%
Itchiness at injection site, moderate	0 0%	0 0%	1 1.2%	0 0%
Itchiness at injection site, mild	11 13.4%	12 14.6%	7 8.5%	10 12.2%
Warmth at injection site, severe	0 0%	0 0%	0 0%	0 0%
Warmth at injection site, moderate	2 2.4%	2 2.4%	1 1.2%	2 2.4%
Warmth at injection site, mild	31 37.8%	25 30.5%	28 34.1%	21 25.6%
Tenderness at injection site, severe	0 0%	0 0%	0 0%	0 0%
Tenderness at injection site, moderate	22 26.8%	15 18.3%	18 22%	10 12.2%
Tenderness at injection site, mild	38 46.3%	44 53.7%	45 54.9%	42 51.2%
Arm motion limitations, severe	0 0%	0 0%	0 0%	0 0%
Arm motion limitations, moderate	3 3.7%	4 4.9%	9 11%	6 7.3%
Arm motion limitations, mild	14 17.1%	13 15.9%	15 18.3%	10 12.2%
Erythema, severe	0 0%	1 1.2%	0 0%	0 0%
Erythema, moderate	5 6.1%	4 4.9%	5 6.1%	3 3.7%
Erythema, mild	26 31.7%	23 28%	21 25.6%	17 20.7%
Edema, severe	0 0%	0 0%	0 0%	0 0%
Edema, moderate	4 4.9%	2 2.4%	1 1.2%	1 1.2%
Edema, mild	16 19.5%	17 20.7%	17 20.7%	11 13.4%

4. Secondary Outcome

Title	Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 14 by Maximum Severity
Description	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.
Time Frame	Days 0-7 after vaccination at Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	65	65	65
Pain at injection site, severe	0 0%	0 0%	0 0%
Pain at injection site, moderate	13 15.9%	12 14.6%	4 4.9%
Pain at injection site, mild	32 39%	37 45.1%	35 42.7%
Itchiness at injection site, severe	0 0%	0 0%	0 0%
Itchiness at injection site, moderate	6 7.3%	6 7.3%	3 3.7%
Itchiness at injection site, mild	26 31.7%	21 25.6%	22 26.8%
Warmth at injection site, severe	0 0%	0 0%	0 0%
Warmth at injection site, moderate	4 4.9%	2 2.4%	2 2.4%
Warmth at injection site, mild	30 36.6%	31 37.8%	27 32.9%
Tenderness at injection site, severe	0 0%	0 0%	0 0%
Tenderness at injection site, moderate	24 29.3%	16 19.5%	14 17.1%
Tenderness at injection site, mild	34 41.5%	43 52.4%	43 52.4%
Arm motion limitations, severe	0 0%	0 0%	0 0%
Arm motion limitations, moderate	7 8.5%	2 2.4%	4 4.9%
Arm motion limitations, mild	21 25.6%	20 24.4%	7 8.5%
Erythema, severe	1 1.2%	3 3.7%	0 0%
Erythema, moderate	13 15.9%	11 13.4%	9 11%
Erythema, mild	19 23.2%	12 14.6%	15 18.3%
Edema, severe	1 1.2%	1 1.2%	0 0%
Edema, moderate	10 12.2%	7 8.5%	5 6.1%
Edema, mild	17 20.7%	18 22%	11 13.4%

5. Secondary Outcome

Title	Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 28 by Maximum Severity
Description	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.
Time Frame	Days 0-7 after vaccination at Day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	64	61	61
Pain at injection site, severe	0 0%	0 0%	0 0%
Pain at injection site, moderate	11 13.4%	3 3.7%	2 2.4%
Pain at injection site, mild	37 45.1%	24 29.3%	17 20.7%
Itchiness at injection site, severe	0 0%	1 1.2%	0 0%
Itchiness at injection site, moderate	6 7.3%	3 3.7%	4 4.9%
Itchiness at injection site, mild	21 25.6%	18 22%	24 29.3%
Warmth at injection site, severe	0 0%	0 0%	0 0%
Warmth at injection site, moderate	4 4.9%	2 2.4%	1 1.2%
Warmth at injection site, mild	26 31.7%	30 36.6%	27 32.9%
Tenderness at injection site, severe	0 0%	1 1.2%	0 0%
Tenderness at injection site, moderate	15 18.3%	3 3.7%	4 4.9%
Tenderness at injection site, mild	44 53.7%	43 52.4%	43 52.4%
Arm motion limitations, severe	0 0%	0 0%	0 0%
Arm motion limitations, moderate	3 3.7%	0 0%	0 0%
Arm motion limitations, mild	16 19.5%	7 8.5%	5 6.1%
Erythema, severe	0 0%	1 1.2%	1 1.2%
Erythema, moderate	17 20.7%	6 7.3%	7 8.5%
Erythema, mild	14 17.1%	15 18.3%	17 20.7%
Edema, severe	1 1.2%	0 0%	0 0%
Edema, moderate	5 6.1%	2 2.4%	5 6.1%
Edema, mild	20 24.4%	13 15.9%	15 18.3%

6. Secondary Outcome

Title	Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following the 6-month Boost by Maximum Severity
Description	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.
Time Frame	Days 0-7 after vaccination at Month 6

Outcome Measure Data

Analysis Population Description

The analysis population includes all participants who received the 6-month booster vaccination.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	60	60	56	56
Pain at injection site, severe	0 0%	1 1.2%	0 0%	1 1.2%
Pain at injection site, moderate	20 24.4%	9 11%	10 12.2%	13 15.9%
Pain at injection site, mild	24 29.3%	29 35.4%	27 32.9%	20 24.4%
Itchiness at injection site, severe	0 0%	0 0%	0 0%	0 0%
Itchiness at injection site, moderate	4 4.9%	2 2.4%	3 3.7%	1 1.2%
Itchiness at injection site, mild	10 12.2%	9 11%	6 7.3%	6 7.3%
Warmth at injection site, severe	0 0%	0 0%	0 0%	0 0%
Warmth at injection site, moderate	0 0%	2 2.4%	4 4.9%	0 0%
Warmth at injection site, mild	17 20.7%	17 20.7%	15 18.3%	18 22%
Tenderness at injection site, severe	0 0%	1 1.2%	0 0%	1 1.2%
Tenderness at injection site, moderate	16 19.5%	9 11%	15 18.3%	14 17.1%
Tenderness at injection site, mild	33 40.2%	42 51.2%	28 34.1%	30 36.6%
Arm motion limitations, severe	0 0%	0 0%	0 0%	1 1.2%
Arm motion limitations, moderate	7 8.5%	6 7.3%	7 8.5%	9 11%
Arm motion limitations, mild	16 19.5%	8 9.8%	14 17.1%	13 15.9%
Erythema, severe	0 0%	0 0%	1 1.2%	0 0%
Erythema, moderate	1 1.2%	3 3.7%	0 0%	1 1.2%
Erythema, mild	4 4.9%	1 1.2%	5 6.1%	1 1.2%
Edema, severe	0 0%	0 0%	0 0%	0 0%
Edema, moderate	3 3.7%	2 2.4%	1 1.2%	2 2.4%
Edema, mild	5 6.1%	2 2.4%	2 2.4%	2 2.4%

7. Secondary Outcome

Title	Number of Participants With Injection Site Edema and Erythema With a Size of Greater Than 120 Millimeters (mm)
Description	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.
Time Frame	Days 0-7 after each vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	67	67	68	67
Edema	1 1.2%	1 1.2%	1 1.2%	0 0%
Erythema	1 1.2%	1 1.2%	2 2.4%	1 1.2%
Edema and/or Erythema	1 1.2%	2 2.4%	2 2.4%	1 1.2%

8. Secondary Outcome

Title	TNA NF50 Geometric Mean Titers (GMT) at Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100.
Description	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.
Time Frame	Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	67	59	59	60
Day 0	0.03	0.03	0.03	0.03
Day 7	0.03	0.03	0.03	0.03
Day 14	0.04	0.04	0.04	0.03
Day 21	0.10	0.06	0.08	0.05
Day 28	0.62	0.06	0.65	0.38
Day 35	0.61	0.17	1.22	0.75
Day 42	0.51	2.85	1.33	0.91
Day 49	0.41	2.19	1.02	0.74
Day 56	0.35	1.62	0.83	0.61
Day 63	0.27	1.27	0.71	0.51
Day 70	0.24	1.00	0.60	0.44
Day 84	0.17	0.64	0.45	0.30
Day 100	0.13	0.44	0.34	0.24

9. Secondary Outcome

Title	Peak Geometric Mean Concentration (GMC) of ELISA Anti-PA IgG Antibody Through Day 100
Description	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.
Time Frame	Day 7 through Day 100

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	67	59	59	60
Geometric Mean (95% Confidence Interval) [µg/mL]	102.32	265.08	182.42	114.42

10. Secondary Outcome

Title	Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 0 by Maximum Severity.
Description	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.
Time Frame	Days 0-7 after vaccination at Day 0

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	67	67	68	67
Fatigue, severe	0 0%	0 0%	0 0%	0 0%
Fatigue, moderate	6 7.3%	6 7.3%	8 9.8%	3 3.7%
Fatigue, mild	9 11%	12 14.6%	12 14.6%	15 18.3%
Muscle aches, severe	0 0%	0 0%	0 0%	0 0%
Muscle aches, moderate	2 2.4%	2 2.4%	7 8.5%	4 4.9%
Muscle aches, mild	15 18.3%	16 19.5%	12 14.6%	14 17.1%
Headache, severe	0 0%	0 0%	0 0%	0 0%
Headache, moderate	6 7.3%	3 3.7%	4 4.9%	3 3.7%
Headache, mild	9 11%	13 15.9%	15 18.3%	18 22%

11. Secondary Outcome

Title	Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 14 by Maximum Severity.
Description	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.
Time Frame	Days 0-7 after vaccination at Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	65	65	65
Fatigue, severe	0 0%	0 0%	0 0%
Fatigue, moderate	7 8.5%	3 3.7%	5 6.1%
Fatigue, mild	17 20.7%	15 18.3%	10 12.2%
Muscle aches, severe	0 0%	0 0%	0 0%
Muscle aches, moderate	7 8.5%	6 7.3%	3 3.7%
Muscle aches, mild	18 22%	13 15.9%	14 17.1%
Headache, severe	0 0%	0 0%	0 0%
Headache, moderate	4 4.9%	4 4.9%	4 4.9%
Headache, mild	14 17.1%	17 20.7%	11 13.4%

12. Secondary Outcome

Title	Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 28 by Maximum Severity.
Description	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.
Time Frame	Days 0-7 after vaccination at Day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	64	61	61
Fatigue, severe	0 0%	0 0%	1 1.2%
Fatigue, moderate	2 2.4%	2 2.4%	0 0%
Fatigue, mild	10 12.2%	7 8.5%	13 15.9%
Muscle aches, severe	0 0%	0 0%	0 0%
Muscle aches, moderate	3 3.7%	3 3.7%	0 0%
Muscle aches, mild	14 17.1%	7 8.5%	12 14.6%
Headache, severe	0 0%	0 0%	0 0%
Headache, moderate	3 3.7%	0 0%	1 1.2%
Headache, mild	8 9.8%	8 9.8%	12 14.6%

13. Secondary Outcome

Title	Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After the 6-month Boost Vaccination by Maximum Severity.
Description	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.
Time Frame	Days 0-7 after vaccination at Month 6

Outcome Measure Data

Analysis Population Description

The analysis population includes all participants who received the 6-month boost vaccination.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	60	60	56	56
Fatigue, severe	0 0%	0 0%	0 0%	0 0%
Fatigue, moderate	6 7.3%	2 2.4%	3 3.7%	1 1.2%
Fatigue, mild	9 11%	10 12.2%	13 15.9%	13 15.9%
Muscle aches, severe	0 0%	0 0%	0 0%	0 0%
Muscle aches, moderate	8 9.8%	2 2.4%	6 7.3%	4 4.9%
Muscle aches, mild	13 15.9%	14 17.1%	14 17.1%	15 18.3%
Headache, severe	0 0%	0 0%	0 0%	0 0%
Headache, moderate	7 8.5%	0 0%	4 4.9%	1 1.2%
Headache, mild	3 3.7%	7 8.5%	9 11%	6 7.3%

14. Secondary Outcome

Title	Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 0 by Maximum Severity
Description	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.
Time Frame	Day 0-7 after vaccination at Day 0

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	67	66	68	67
Fever, severe	0 0%	0 0%	0 0%	0 0%
Fever, moderate	0 0%	0 0%	0 0%	0 0%
Fever, mild	0 0%	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 14 by Maximum Severity
Description	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.
Time Frame	Day 0-7 after vaccination at Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	65	65	65
Fever, severe	0 0%	0 0%	0 0%
Fever, moderate	0 0%	0 0%	0 0%
Fever, mild	0 0%	0 0%	0 0%

16. Secondary Outcome

Title	Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 28 by Maximum Severity
Description	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.
Time Frame	Day 0-7 after vaccination at Day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	64	60	61
Fever, severe	0 0%	0 0%	0 0%
Fever, moderate	0 0%	0 0%	0 0%
Fever, mild	0 0%	0 0%	0 0%

17. Secondary Outcome

Title	Number of Participants Reporting Fever in the Eight Days After the 6-month Boost Vaccination by Maximum Severity
Description	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.
Time Frame	Day 0-7 after vaccination at Month 6

Outcome Measure Data

Analysis Population Description

The analysis population includes all participants who received the 6-month boost vaccination and recorded oral temperatures.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	60	58	55	56
Fever, severe	0 0%	0 0%	1 1.2%	0 0%
Fever, moderate	0 0%	0 0%	0 0%	0 0%
Fever, mild	0 0%	0 0%	0 0%	1 1.2%

18. Secondary Outcome

Title	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)
Description	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.
Time Frame	Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	67	59	59	60
Day 7	1 1.2%	0 0%	1 1.2%	0 0%
Day 14	4 4.9%	2 2.4%	0 0%	1 1.2%
Day 21	25 30.5%	9 11%	21 25.6%	11 13.4%
Day 28	65 79.3%	9 11%	57 69.5%	46 56.1%
Day 35	65 79.3%	24 29.3%	59 72%	54 65.9%
Day 42	65 79.3%	59 72%	59 72%	57 69.5%
Day 49	61 74.4%	59 72%	59 72%	56 68.3%
Day 56	60 73.2%	59 72%	59 72%	55 67.1%
Day 63	57 69.5%	59 72%	59 72%	53 64.6%
Day 70	54 65.9%	58 70.7%	58 70.7%	53 64.6%
Day 84	44 53.7%	56 68.3%	57 69.5%	49 59.8%
Day 100	38 46.3%	52 63.4%	54 65.9%	48 58.5%

19. Secondary Outcome

Title	TNA NF50 Peak Geometric Mean Titer (GMT) Antibody Response Through Day 100
Description	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.
Time Frame	Day 7 through Day 100

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14	Arm B: 0.50mL BioThrax, Days 0, 28	Arm C: 0.50mL BioThrax, Days 0, 14, 28	Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost	BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
Measure Participants	67	59	59	60
Geometric Mean (95% Confidence Interval) [titer]	0.74	2.99	1.48	1.00

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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.
Arm/Group Title	Arm A: 0.50mL BioThrax, Days 0, 14		Arm B: 0.50mL BioThrax, Days 0, 28		Arm C: 0.50mL BioThrax, Days 0, 14, 28		Arm D: 0.25mL BioThrax, Days 0, 14, 28
Arm/Group Description	BioThrax 0.50ml subcutaneously on Days 0, 14, and 0.50mL BioThrax intramuscularly at 6 month boost		BioThrax 0.50ml subcutaneously on Days 0, 28, and 0.50mL BioThrax intramuscularly at 6 month boost		BioThrax 0.50ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost		BioThrax 0.25ml subcutaneously on Days 0, 14, 28, and 0.50mL BioThrax intramuscularly at 6 month boost
All Cause Mortality
	Arm A: 0.50mL BioThrax, Days 0, 14		Arm B: 0.50mL BioThrax, Days 0, 28		Arm C: 0.50mL BioThrax, Days 0, 14, 28		Arm D: 0.25mL BioThrax, Days 0, 14, 28
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A: 0.50mL BioThrax, Days 0, 14		Arm B: 0.50mL BioThrax, Days 0, 28		Arm C: 0.50mL BioThrax, Days 0, 14, 28		Arm D: 0.25mL BioThrax, Days 0, 14, 28
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		2/82 (2.4%)		1/82 (1.2%)		0/82 (0%)
Infections and infestations
Localised infection	0/82 (0%)	0	1/82 (1.2%)	1	0/82 (0%)	0	0/82 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/82 (0%)	0	1/82 (1.2%)	1	0/82 (0%)	0	0/82 (0%)	0
Nervous system disorders
Convulsion	0/82 (0%)	0	0/82 (0%)	0	1/82 (1.2%)	1	0/82 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A: 0.50mL BioThrax, Days 0, 14		Arm B: 0.50mL BioThrax, Days 0, 28		Arm C: 0.50mL BioThrax, Days 0, 14, 28		Arm D: 0.25mL BioThrax, Days 0, 14, 28
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	82/82 (100%)		82/82 (100%)		82/82 (100%)		82/82 (100%)
Cardiac disorders
Bradycardia	2/82 (2.4%)	2	4/82 (4.9%)	4	8/82 (9.8%)	11	7/82 (8.5%)	11
General disorders
Fatigue	38/82 (46.3%)	58	33/82 (40.2%)	48	40/82 (48.8%)	74	40/82 (48.8%)	70
Vaccination site pain	71/82 (86.6%)	155	72/82 (87.8%)	168	72/82 (87.8%)	185	71/82 (86.6%)	154
Vaccination site pruritus	52/82 (63.4%)	74	44/82 (53.7%)	64	47/82 (57.3%)	81	48/82 (58.5%)	88
Vaccination site warmth	54/82 (65.9%)	102	49/82 (59.8%)	88	50/82 (61%)	124	50/82 (61%)	120
Tenderness	81/82 (98.8%)	205	79/82 (96.3%)	208	80/82 (97.6%)	251	78/82 (95.1%)	247
Vaccination site erythema	53/82 (64.6%)	84	48/82 (58.5%)	86	47/82 (57.3%)	91	42/82 (51.2%)	94
Vaccination site swelling	44/82 (53.7%)	74	44/82 (53.7%)	63	40/82 (48.8%)	73	40/82 (48.8%)	70
Vaccination site bruising	6/82 (7.3%)	6	10/82 (12.2%)	12	4/82 (4.9%)	4	5/82 (6.1%)	5
Vaccination site erythema	4/82 (4.9%)	4	6/82 (7.3%)	7	4/82 (4.9%)	4	3/82 (3.7%)	3
Vaccination site nodule	63/82 (76.8%)	109	64/82 (78%)	107	66/82 (80.5%)	145	60/82 (73.2%)	129
Vessel puncture site bruise	5/82 (6.1%)	5	2/82 (2.4%)	2	3/82 (3.7%)	3	6/82 (7.3%)	6
Infections and infestations
Nasopharyngitis	5/82 (6.1%)	5	6/82 (7.3%)	6	5/82 (6.1%)	5	6/82 (7.3%)	6
Upper respiratory tract infection	9/82 (11%)	9	18/82 (22%)	19	13/82 (15.9%)	14	10/82 (12.2%)	11
Investigations
Respiratory rate increased	21/82 (25.6%)	27	25/82 (30.5%)	34	26/82 (31.7%)	37	22/82 (26.8%)	30
Musculoskeletal and connective tissue disorders
Myalgia	47/82 (57.3%)	75	35/82 (42.7%)	58	38/82 (46.3%)	75	42/82 (51.2%)	75
Joint range of motion decreased	44/82 (53.7%)	79	39/82 (47.6%)	59	48/82 (58.5%)	85	43/82 (52.4%)	63
Nervous system disorders
Headache	32/82 (39%)	49	30/82 (36.6%)	44	42/82 (51.2%)	68	40/82 (48.8%)	66
Dizziness	0/82 (0%)	0	2/82 (2.4%)	2	4/82 (4.9%)	5	5/82 (6.1%)	5
Headache	7/82 (8.5%)	8	5/82 (6.1%)	6	5/82 (6.1%)	6	4/82 (4.9%)	4
Vascular disorders
Hypertension	1/82 (1.2%)	1	4/82 (4.9%)	7	5/82 (6.1%)	7	2/82 (2.4%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.