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| ID | Type | Description | Link |
|---|---|---|---|
| HHSO100200700037C | Other Grant/Funding Number | Department of Health and Human Services |
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| Name | Class |
|---|---|
| Department of Health and Human Services | FED |
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The purpose of this Phase 3 clinical trial is to evaluate the immunogenicity and safety of BioThrax anthrax vaccine in healthy adults following 3 doses of BioThrax. Results of this study will be used to support a post-exposure prophylaxis (PEP) indication for BioThrax.
This study will be conducted in the United States (U.S.), in 200 healthy male and female volunteer subjects ages 18 to 65 years.
The duration of study participation for each individual subject will be approximately 128 days (4.25 months), including a screening period of approximately 28 days followed by 100 days on study.
BioThrax® (also called Anthrax Vaccine Adsorbed or AVA) is the only FDA-licensed vaccine for the prevention of anthrax infection. This study will evaluate the immunogenicity of the vaccine using a post-exposure vaccination schedule. Correlations will be drawn to immunogenicity and survival data from animal models to demonstrate that BioThrax® can elicit a protective immune response for PEP.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BioThrax (0.5 mL, on days 0, 14, and 28) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BioThrax | Biological | BioThrax, 0.5 mL administered subcutaneously on days 0, 14, and 28. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value at Day 63 (5 Weeks Following the Third Vaccination on Day 28). | Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. | Day 63 +/- 2 days |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value at Day 70. | Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert Hopkins, MD, MPH, TM | Emergent BioSolutions Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Miami Research Associates | Miami | Florida | 33143 | United States | ||
| Rochester Clinical Research |
All enrolled participants met the inclusion and exclusion criteria.
Participants were enrolled from 9 November 2011 to 9 May 2012 at four medical centers in the U.S.
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| ID | Title | Description |
|---|---|---|
| FG000 | BioThrax | Participants 18 to 65 years of age who received at least one dose of BioThrax (0.5 mL) subcutaneously (SC). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants 18 to 65 years of age who received all three doses of BioThrax within the allowable time window and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by Sponsor) on Day 63 were excluded.
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| ID | Title | Description |
|---|---|---|
| BG000 | BioThrax - Site 01 | Subjects from Site 01 who received all three doses of BioThrax within the allowable time window and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by Sponsor) on Day 63 were excluded. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value at Day 63 (5 Weeks Following the Third Vaccination on Day 28). | Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. | Subjects who received all three doses of BioThrax within the allowable time window and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by Sponsor) on Day 63 were excluded. | Posted | Mean | 95% Confidence Interval | percentage of participants | Day 63 +/- 2 days |
|
Adverse event data were collected from the time of screening up to 100 days post dose.
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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 | ITT Population | Participants 18 to 65 years of age who received at least one dose of BioThrax (0.5 mL) subcutaneously (SC). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Obesity | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment | The participant was hospitalized due to elective gastric bypass for morbid obesity. The event was assessed by the principal investigator as not related to vaccination. The event resolved without sequelae, and the subject completed the study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Robert Hopkins | Emergent BioSolutions | (301) 944-0136 | hopkinsr@ebsi.com |
Not provided
| ID | Term |
|---|---|
| D000881 | Anthrax |
| ID | Term |
|---|---|
| D016863 | Bacillaceae Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
Not provided
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| ID | Term |
|---|---|
| C493276 | Biothrax |
| D022122 | Anthrax Vaccines |
| ID | Term |
|---|---|
| D001428 | Bacterial Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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| Day 70 +/- 2 days |
| Average Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value Between Days 63 and 100 (Inclusive). | Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. | Days 63 to 100 |
| Incidence of Injection Site Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Injection site reactions (warmth, tenderness, itching, pain, arm motion limitation, redness, lump, swelling, and bruise) were evaluated by using a web-enabled subject diary. Subjects assessed the severity of warmth, tenderness, itching, pain, arm motion limitation, lump, and bruise as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of redness and swelling were based on the diameter of the affected area. Severe injection site reactions were recorded as adverse events by the investigator site staff after confirmation with the subject. | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). |
| Percentage of Injection Site Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Injection site reactions (warmth, tenderness, itching, pain, arm motion limitation, redness, lump, swelling, and bruise) were evaluated by using a web-enabled subject diary. Subjects assessed the severity of warmth, tenderness, itching, pain, arm motion limitation, lump, and bruise as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of redness and swelling were based on the diameter of the affected area. Severe injection site reactions were recorded as adverse events by the investigator site staff after confirmation with the subject. | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). |
| Incidence of Systemic Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Systemic reactions (fatigue/ tiredness, muscle ache, headache, and fever) were evaluated by using a web-enabled subject diary. Subjects assessed severity as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of fever was assessed using a grading scale. Severe systemic reactions were to be recorded as adverse events by the investigator site staff after confirmation with the subject. | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). |
| Percentage of Systemic Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Systemic reactions (fatigue/ tiredness, muscle ache, headache, and fever) were evaluated by using a web-enabled subject diary. Subjects assessed severity as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of fever was assessed using a grading scale. Severe systemic reactions were to be recorded as adverse events by the investigator site staff after confirmation with the subject. | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). |
| Rochester |
| New York |
| 14609 |
| United States |
| Coastal Carolina Research Center | Mt. Pleasant | South Carolina | 29464 | United States |
| Jean Brown Research | Salt Lake City | Utah | 84124 | United States |
| BG001 |
| BioThrax - Site 02 |
Subjects from Site 02 who received all three doses of BioThrax within the allowable time window and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by Sponsor) on Day 63 were excluded. |
| BG002 | BioThrax - Site 03 | Subjects from Site 03 who received all three doses of BioThrax within the allowable time window and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by Sponsor) on Day 63 were excluded. |
| BG003 | BioThrax - Site 04 | Subjects from Site 04 who received all three doses of BioThrax within the allowable time window and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by Sponsor) on Day 63 were excluded. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
Participants 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population.
| OG001 | BioThrax - Male | Male participants 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population.. |
| OG002 | BioThrax - Female | Female participants 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population.. |
| OG003 | BioThrax - ≤ 30 Years of Age | Participants ≤ 30 Years of Age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population.. |
| OG004 | BioThrax- > 30 Years of Age | Participants > 30 Years of Age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population. |
| OG005 | BioThrax - Caucasian | Caucasian participants 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population.. |
| OG006 | BioThrax - Non-Caucasian | Non-Caucasian participants 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population.. |
| OG007 | BioThrax - Site 01 | Participants enrolled at Site 01 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population. |
| OG008 | BioThrax - Site 02 | Participants enrolled at Site 02 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population. |
| OG009 | BioThrax - Site 03 | Participants enrolled at Site 03 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population. |
| OG010 | BioThrax - Site 04 | Participants enrolled at Site 04 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days. Subjects with key protocol deviations that may have impacted assessment of immune response or sample testing (as determined by the Sponsor) on Day 63 were excluded from the Primary Per-Protocol Population. |
|
|
| Secondary | Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value at Day 70. | Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. | Participants 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 70 ± 2 days. | Posted | Least Squares Mean | 95% Confidence Interval | percentage of participants | Day 70 +/- 2 days |
|
|
|
| Secondary | Average Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value Between Days 63 and 100 (Inclusive). | Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. | Participants 18 to 65 years of age who received all three doses of BioThrax (0.5 mL) subcutaneously (SC) within the allowable time window (±2 days for Days 14 and 28) and had a blood sample collected for immunogenicity testing on Day 63 ± 2 days, Day 70 ± 2 days, Day 84 ± 3 days, and Day 100 ± 3 days, inclusive. | Posted | Mean | 95% Confidence Interval | percentage of participants | Days 63 to 100 |
|
|
|
| Secondary | Incidence of Injection Site Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Injection site reactions (warmth, tenderness, itching, pain, arm motion limitation, redness, lump, swelling, and bruise) were evaluated by using a web-enabled subject diary. Subjects assessed the severity of warmth, tenderness, itching, pain, arm motion limitation, lump, and bruise as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of redness and swelling were based on the diameter of the affected area. Severe injection site reactions were recorded as adverse events by the investigator site staff after confirmation with the subject. | The reporting group was subjects who had any diary data available during the 7-day-post-vaccination period (i.e., n=196, n=196, and n=193, for the1st, 2nd, and 3rd post-vaccination periods, respectively). | Posted | Number | participants | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). |
|
|
|
| Secondary | Percentage of Injection Site Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Injection site reactions (warmth, tenderness, itching, pain, arm motion limitation, redness, lump, swelling, and bruise) were evaluated by using a web-enabled subject diary. Subjects assessed the severity of warmth, tenderness, itching, pain, arm motion limitation, lump, and bruise as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of redness and swelling were based on the diameter of the affected area. Severe injection site reactions were recorded as adverse events by the investigator site staff after confirmation with the subject. | The reporting group was subjects who had any diary data available during the 7-day-post-vaccination period (i.e., n=196, n=196, and n=193, for the1st, 2nd, and 3rd post-vaccination periods, respectively). | Posted | Number | percentage of participants | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). |
|
|
|
| Secondary | Incidence of Systemic Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Systemic reactions (fatigue/ tiredness, muscle ache, headache, and fever) were evaluated by using a web-enabled subject diary. Subjects assessed severity as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of fever was assessed using a grading scale. Severe systemic reactions were to be recorded as adverse events by the investigator site staff after confirmation with the subject. | The reporting group was subjects who had any diary data available during the 7-day-post-vaccination period (i.e., n=196, n=196, and n=193, for the1st, 2nd, and 3rd post-vaccination periods, respectively). | Posted | Number | participants | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). |
|
|
|
| Secondary | Percentage of Systemic Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Systemic reactions (fatigue/ tiredness, muscle ache, headache, and fever) were evaluated by using a web-enabled subject diary. Subjects assessed severity as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of fever was assessed using a grading scale. Severe systemic reactions were to be recorded as adverse events by the investigator site staff after confirmation with the subject. | The reporting group was subjects who had any diary data available during the 7-day-post-vaccination period (i.e., n=196, n=196, and n=193, for the1st, 2nd, and 3rd post-vaccination periods, respectively). | Posted | Number | percentage of participants | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). |
|
|
|
| 2 |
| 200 |
| 109 |
| 200 |
|
| Aura | Nervous system disorders | MedDRA (14.0) | Systematic Assessment | The participant experienced a visual aura without headache. The event was assessed by the principal investigator as not related to vaccination. The event resolved without sequelae, and the subject completed the study. |
|
| Headache | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
Sponsor is responsible for public disclosure of study data. Any proposed publication is subject to review agreed between Biomedical Advanced Research and Development Authority (BARDA)and Emergent; between Emergent and the contract research organizations (CROs)/vendors; and between the CROs and the site Principal Investigator. Data are the property of the sponsor and cannot be published without prior authorization from the sponsor, but data and publication thereof will not be unduly withheld.
| D007239 | Infections |
| Tenderness |
|
| Itching |
|
| Pain |
|
| Arm Motion Limitation |
|
| Redness |
|
| Swelling |
|
| Lump |
|
| Bruise |
|
| Tenderness |
|
| Itching |
|
| Pain |
|
| Arm Motion Limitation |
|
| Redness |
|
| Swelling |
|
| Lump |
|
| Bruise |
|
| Muscle Ache |
|
| Headache |
|
| Fever |
|
| Muscle Ache |
|
| Headache |
|
| Fever |
|