VELOCITY: An Anthrax Vaccine Clinical Study

• Sponsor: Emergent BioSolutions (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03877926
• Collaborator: Biomedical Advanced Research and Development Authority (U.S. Fed)
• Enrollment: 3,862
• Locations: 35
• Arms: 4
• Actual Duration (Months): 16.9
• Patients Per Site: 110.3
• Patients Per Site Per Month: 6.5

Study Details

Study Description

Brief Summary

This study is designed to evaluate the lot consistency (using three consecutively manufactured lots), safety, and ability of the AV7909 anthrax vaccine to generate an immune response in healthy adults and compare the response to that induced by the currently licensed vaccine, BioThrax®, (Anthrax Vaccine Adsorbed; AVA) for post-exposure of anthrax disease.

Condition or Disease	Intervention/Treatment	Phase
Anthrax	Biological: AV7909; Biological: BioThrax	Phase 3

Detailed Description

This is a Phase 3, multicenter, randomized, double-blind, parallel-group trial designed to evaluate the lot consistency (using three consecutively manufactured lots), immunogenicity, and safety of AV7909 administered in healthy adults for an indication of postexposure prophylaxis (PEP) of anthrax.

Healthy adults between 18 and 65 years of age (inclusive) will sign and date an informed consent form and then be screened for eligibility for participation in the study 2 to 28 days prior to randomization. Participants meeting the entry criteria will be randomized 2:2:2:1 to one of four study groups on Day 1. Randomization will be stratified by site.

Participants will be evaluated for safety through Day 64 [or the early withdrawal visit (EWV)], as assessed by clinical laboratory tests (hematology, serum chemistry, and urinalysis), monitoring of Adverse Events (AE) including Serious Adverse Events (SAE) and Adverse Events of Special Interest (AESI), vital signs, and physical examinations. Adverse Events of Special Interest are adverse events associated with autoimmune disease as defined by the Center for Biologics Evaluation and Research, and might represent a safety signal for vaccine-associated autoimmunity. Reactogenicity (solicited systemic and injection site reactions) will be assessed daily by the participants using electronic diaries (e-diaries) after each vaccination.

Information on the use of medications will be collected at each study visit. In addition, blood samples for auto-antibody assessment will be taken at Day 1 predose and Day 64 (or Early Withdrawal Visit).

Participants who receive at least one dose of vaccine but who for any reason discontinue vaccinations prematurely will be asked to participate in the further planned study visits up to Day 64 for safety assessment only.

Participants who receive at least one dose of vaccine will also be asked to participate in safety follow-up phone calls occurring on Day 43, Month 4, Month 7, Month 10, and Month 13 (nominally 0.5, 3, 6, 9, and 12 months after the last vaccination) to collect information on AEs, SAEs and any potential AESIs. Based on responses at these phone contacts, participants may be asked to return to the clinic for an unscheduled visit to provide blood samples for auto-antibody testing to investigate reports of potential AESIs.

Independent safety oversight will be provided by a Data Safety Monitoring Board, which will be notified of significant AEs as determined by the Medical Monitor on an ongoing basis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3862 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Randomized, Double-blind, Parallel-group Trial to Evaluate the Lot Consistency, Immunogenicity, and Safety of AV7909 for Postexposure Prophylaxis of Anthrax in Healthy Adults
• Actual Study Start Date: Mar 11, 2019
• Actual Primary Completion Date: Aug 6, 2020
• Actual Study Completion Date: Aug 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AV7909 Lot 1 Participants meeting the entry criteria will be randomized 2:2:2:1 to one of four study groups. Groups 1 to 3 will each receive one of the three consecutively manufactured lots of AV7909, per the study visit schedule.	Biological: AV7909; AV7909 consists of Anthrax Vaccine Adsorbed (AVA) drug substance and CPG 7909 adjuvant. AVA drug substance in AV7909 is similar in composition and manufactured using the same process as commercial BioThrax® vaccine. BioThrax is licensed for post-exposure prophylaxis of anthrax disease. CPG 7909 is an immunostimulatory synthetic oligodeoxynucleotide that functions as an adjuvant. It is designed to induce an enhanced immune response.
Experimental: AV7909 Lot 2 Participants meeting the entry criteria will be randomized 2:2:2:1 to one of four study groups. Groups 1 to 3 will each receive one of the three consecutively manufactured lots of AV7909, per the study visit schedule.	Biological: AV7909; AV7909 consists of Anthrax Vaccine Adsorbed (AVA) drug substance and CPG 7909 adjuvant. AVA drug substance in AV7909 is similar in composition and manufactured using the same process as commercial BioThrax® vaccine. BioThrax is licensed for post-exposure prophylaxis of anthrax disease. CPG 7909 is an immunostimulatory synthetic oligodeoxynucleotide that functions as an adjuvant. It is designed to induce an enhanced immune response.
Experimental: AV7909 Lot 3 Participants meeting the entry criteria will be randomized 2:2:2:1 to one of four study groups. Groups 1 to 3 will each receive one of the three consecutively manufactured lots of AV7909, per the study visit schedule.	Biological: AV7909; AV7909 consists of Anthrax Vaccine Adsorbed (AVA) drug substance and CPG 7909 adjuvant. AVA drug substance in AV7909 is similar in composition and manufactured using the same process as commercial BioThrax® vaccine. BioThrax is licensed for post-exposure prophylaxis of anthrax disease. CPG 7909 is an immunostimulatory synthetic oligodeoxynucleotide that functions as an adjuvant. It is designed to induce an enhanced immune response.
Active Comparator: BioThrax Participants meeting the entry criteria will be randomized 2:2:2:1 to one of four study groups. In Group 4, one lot of BioThrax® vaccine will be administered, per the study visit schedule.	Biological: BioThrax; BioThrax vaccine (Anthrax Vaccine Adsorbed; AVA) is licensed for post-exposure prophylaxis of anthrax disease.

Outcome Measures

Primary Outcome Measures

1. Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) 50% Neutralization Factor (NF50) at Day 64 [Day 64 (seven weeks after second AV7909 vaccination)]

   GMT of TNA NF50 at Day 64 in AV7909 study groups (Lots 1, 2 and 3) and BioThrax group. The outcome measure in AV7909 study groups was assessed for AV7909 lot-to-lot consistency, which was based on GMT TNA NF50 response at Day 64, wherein the 95% confidence interval (CI) for ratios of geometric mean titer (GMT) of TNA NF50 at Day 64 (seven weeks after second AV7909 vaccination) for each of the three AV7909 lot-to-lot comparisons had to be within equivalence margin of 0.5 and 2.0.

2. Percentage of Participants in AV7909 Lot 1, Lot 2 and Lot 3 Groups Achieving a TNA NF50 ≥0.56 on Day 64 [Day 64 (seven weeks after second AV7909 vaccination)]

   Proportion of participants with TNA NF50 ≥0.56 at Day 64 in each AV7909 study groups (Lot 1, Lot 2, Lot 3). The assessment of the immune response in each study group was pre-defined as the lower bound of the two-sided 95% CI to be ≥40% for the percentage of AV7909 participants in each of the three lots achieving a TNA NF50 ≥0.56 at seven weeks after second AV7909 vaccination (Day 64).

3. Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.56 on Day 64 [Day 64 (seven weeks after second AV7909 vaccination)]

   Percentage of AV7909 participants (from all three AV7909 study groups pooled) achieving a TNA NF50 ≥0.56 on Day 64 (seven weeks after second AV7909 vaccination). The assessment of the immune response in AV7909 participants was pre-defined as the lower bound of the two-sided 95% CI for proportion of AV7909 participants with TNA NF50 ≥0.56 at Day 64 ≥40%.

4. Percentage of AV7909 Participants and BioThrax Participants With TNA NF50 ≥0.29 at Day 64 [Day 64 (seven weeks after second AV7909 vaccination; five weeks after third BioThrax vaccination)]

   Proportion of AV7909 participants (in each AV7909 study groups) and BioThrax participants who achieved TNA NF50 ≥0.29 at Day 64. Non-inferiority of AV7909 vaccine to BioThrax vaccine at Day 64 was assessed as determined by the two-sided lower bound for the 95% CI of the difference in the percentage of AV7909 participants (three lots pooled) with a TNA NF50 ≥0.29 and the percentage of BioThrax participants with a TNA NF50 ≥0.29 being greater than -15%.

5. Incidence of Serious Adverse Events [Day 1 though Day 394]

   Number of AV7909 participants or BioThrax participants who received at least one vaccination and reported serious adverse event(s) (SAEs) from the time of the first vaccination on Day 1 through Day 394.

Secondary Outcome Measures

1. Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.15 on Day 29. [Day 29 (two weeks after second AV7909 vaccination)]

   Proportion of AV7909 participants (in each AV7909 study group) who achieved TNA NF50 ≥0.15 at Day 29 (two weeks after second AV7909 vaccination). Assessment of the lower bound of the two-sided 95% CI to be ≥67% for the percentage of AV7909 participants in AV7909 study groups 1-3 (Pooled AV7909) achieving a TNA NF50 ≥0.15 on Day 29 was performed.

2. Incidence of Adverse Events [Day 1 through Day 64]

   Number of AV7909 or BioThrax participants who received at least one vaccination and had at least one adverse event reported from the time of the first vaccination on Day 1 through Day 64.

3. Incidence of Adverse Events of Special Interest (Events of Autoimmune Etiology) [Day 1 through Day 394]

   Incidence of adverse events of special interest (AESIs; events of autoimmune etiology) from the time of the first vaccination on Day 1 through Day 394 in participants who received at least one dose of AV7909 (Lot 1, Lot 2 or Lot 3) or BioThrax vaccines.

4. Incidence of Solicited Systemic Reactogenicity Events [Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day)]

   Incidence of any solicited systemic reactogenicity reaction after any AV7909 or BioThrax vaccination.

5. Incidences of Solicited Injection Site Reactogenicity Events [Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day)]

   Incidence of any solicited injection site reactogenicity reaction after any AV7909 (Lots 1, 2 or 3) or BioThrax vaccination.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Written informed consent obtained from the participant (dated and signed).

2. Healthy condition as established by medical history and clinical examination before entering into the study.

3. A male or female aged 18 to 65 years, inclusive, at the time of informed consent.

4. Body mass index (BMI) ≤35.0 kg/m^2 at Screening visit.

5. Have adequate venous access for phlebotomies.

6. For a woman of childbearing potential (WOCBP), negative serum pregnancy test at Screening and negative urine pregnancy test prevaccination on Day 1, not currently breastfeeding, and no intention to become pregnant during the study through Month 13. Every female participant is considered to be a WOCBP unless surgically sterile (bilateral oophorectomy or bilateral salpingectomy or hysterectomy) OR postmenopausal (defined as >12 consecutive months without menses and screening follicle-stimulating hormone >30 mIU/mL). Women who are not of childbearing potential are allowed to enroll if they are surgically sterile or postmenopausal as defined above.

Exclusion Criteria:

1. Use of any investigational or nonregistered product (drug, vaccine, device, or combination product) within 30 days preceding the dose of study vaccine, or planned use during the study through Month 13.

2. Positive test result on urine drug screen, any evidence of ongoing drug abuse or dependence (including alcohol), or recent history (over the past five years) of treatment for alcohol or drug abuse.

3. Chronic administration (defined as >14 days) of immunosuppressants or other immune-modifying drugs (includes oral or parenteral corticosteroids, for example, a glucocorticoid dose exceeding 10 mg/day prednisone or equivalent) within six months prior to the vaccine dose; inhalation use (for example, for seasonal allergies) is permitted.

4. Planned administration of any commercially-available vaccine from seven days prior to the first study vaccination through two weeks after the last vaccination.

5. Previous anaphylactic reaction, severe systemic response, or serious hypersensitivity to a prior immunization or a known allergy to synthetic Oligodeoxynucleotides, aluminum, formaldehyde, benzethonium chloride (phemerol), or latex.

6. History of anthrax disease, suspected exposure to anthrax, or previous vaccination with any anthrax vaccine.

7. Have a tattoo/scar/birthmark or any other skin condition affecting the deltoid area that may interfere with injection site assessments.

8. A positive blood test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) HIV-1 or HIV-2 antibodies.

9. Any confirmed or suspected immunodeficiency condition (congenital or secondary) or autoimmune disease based on medical history and Physical Exam, for example, Guillain-Barré.

10. A family history of congenital or hereditary immunodeficiency.

11. Major congenital defects or serious chronic illness, including any cancer other than the following: a) any non-metastatic cancer (excluding hematologic malignancies) or melanoma of which the participant has been disease-free for at least five years and b) localized skin cancer, resected (including squamous cell and basal cell carcinomas).

12. Acute disease at the time of enrollment. Note that screening lab tests may be delayed to allow the resolution of a transient acute condition or the subject may be rescreened.

13. Any medical condition that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study.

14. Any planned elective surgery during the study through 12 months after the last vaccination.

15. Planned receipt of immunoglobulins and/or any blood products within the three months preceding study enrollment or at any point during the study period until after the final safety phone contact.

16. Woman of childbearing potential refusing to practice an adequate method of contraception from at least one month before Day 1 and continuing through Month 13.

An adequate method of contraception is defined as abstinence from sexual intercourse; prior bilateral tubal ligation; monogamous relationship with a vasectomized partner (vasectomy performed at least six months prior to the participant's screening visit); or any of these forms of birth control: pill, intrauterine device (IUD), implantable or injectable contraceptive (for example, Norplant® or Depo-Provera®), removable device (for example, NuvaRing® or Evra® patch), or double-barrier method (condom with spermicide, diaphragm with spermicide). The Principal Investigator and/or designee will discuss with the participant the need to use adequate contraception consistently and correctly and document such conversation in the participant's chart. In addition, the Principal Investigator and/or designee will instruct the participant to call immediately if the selected contraception method is discontinued or if pregnancy is known or suspected.

1. Member or family member of the investigator site team.

2. Previously served in the military any time after 1990 and/or plan to enlist in the military at any time from screening through the final telephone contact.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Achieve Clinical Research, LLC	Birmingham	Alabama	United States	35216
2	Optimal Research, LLC	Huntsville	Alabama	United States	35802
3	Coastal Clinical Research, an AMR company	Mobile	Alabama	United States	36608
4	Central Phoenix Medical Clinic, LLC	Phoenix	Arizona	United States	85020
5	Clinical Research Consortium, an AMR company	Tempe	Arizona	United States	85283
6	California Research Foundation	San Diego	California	United States	92103
7	Optimal Research, LLC	San Diego	California	United States	92108
8	Research Centers of America	Hollywood	Florida	United States	33024
9	Optimal Research, LLC	Melbourne	Florida	United States	32934
10	New Horizon Research Center, Inc	Miami	Florida	United States	33175
11	Meridian Clinical Research, LLC	Savannah	Georgia	United States	31406
12	Advanced Clinical Research	Boise	Idaho	United States	83642
13	Christie Clinic, LLC	Champaign	Illinois	United States	61820
14	Optimal Research, LLC	Peoria	Illinois	United States	61614
15	The Iowa Clinic, PC	West Des Moines	Iowa	United States	50266
16	Heartland Research Associates, LLC	Augusta	Kansas	United States	67010
17	Hutchinson Clinic	Hutchinson	Kansas	United States	67502
18	Johnson County Clin-Trials, LLC	Lenexa	Kansas	United States	66219
19	Heartland Research Associates, LLC	Wichita	Kansas	United States	67205
20	Benchmark Research New Orleans	Metairie	Louisiana	United States	70006
21	Optimal Research, LLC	Rockville	Maryland	United States	20850
22	The Center for Pharmaceutical Research, an AMR company	Kansas City	Missouri	United States	64114
23	Meridian Clinical Research, LLC	Omaha	Nebraska	United States	68134
24	Clinical Research Center of Nevada LLC	Las Vegas	Nevada	United States	89104
25	Rapid Medical Research, Inc.	Cleveland	Ohio	United States	44122
26	Aventiv Research Inc.	Grove City	Ohio	United States	43123
27	Lynn Institute of Norman	Norman	Oklahoma	United States	73072
28	Coastal Carolina Research Center, Inc	Mount Pleasant	South Carolina	United States	29464
29	Spartanburg Medical Research	Spartanburg	South Carolina	United States	29303
30	Clinical Research Associates, Inc.	Nashville	Tennessee	United States	37203
31	Tekton Research	Austin	Texas	United States	78745
32	Benchmark Research	Fort Worth	Texas	United States	76135
33	Benchmark Research San Angelo	San Angelo	Texas	United States	76904
34	Martin Diagnostic Clinic	Tomball	Texas	United States	77375
35	Advanced Clinical Research	West Jordan	Utah	United States	84088

Sponsors and Collaborators

• Emergent BioSolutions
• Biomedical Advanced Research and Development Authority

Investigators

• Study Director: Gideon Akintunde, MD, Emergent BioSolutions

Study Documents (Full-Text)

• Study Protocol - Mar 14, 2019
• Statistical Analysis Plan - Sep 15, 2020
• Informed Consent Form - Jan 29, 2019

More Information

Publications

None provided.

• Responsible Party: Emergent BioSolutions
• ClinicalTrials.gov Identifier: NCT03877926
• Other Study ID Numbers: EBS.AVA.212
• First Posted: Mar 18, 2019
• Last Update Posted: Dec 21, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Emergent BioSolutions: Anthrax; AV7909; BioThrax; Bacillus anthracis; Anthrax Vaccine Adsorbed; Post-exposure Prophylaxis; Vaccine; CPG 7909; Adjuvant
• Additional relevant MeSH terms: Anthrax

Study Results

Participant Flow

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3	BioThrax
Arm/Group Description	Eligible participants randomized to receive AV7909 Lot 1. AV7909: AV7909 consists of Anthrax Vaccine Adsorbed (AVA) drug substance and CPG 7909 adjuvant. AVA drug substance in AV7909 is similar in composition and manufactured using the same process as commercial BioThrax® vaccine. CPG 7909 is an immunostimulatory synthetic oligodeoxynucleotide that functions as an adjuvant.	Eligible participants randomized to receive AV7909 Lot 2. AV7909: AV7909 consists of Anthrax Vaccine Adsorbed (AVA) drug substance and CPG 7909 adjuvant. AVA drug substance in AV7909 is similar in composition and manufactured using the same process as commercial BioThrax vaccine. CPG 7909 is an immunostimulatory synthetic oligodeoxynucleotide that functions as an adjuvant.	Eligible participants randomized to receive AV7909 Lot 3. AV7909: AV7909 consists of Anthrax Vaccine Adsorbed (AVA) drug substance and CPG 7909 adjuvant. AVA drug substance in AV7909 is similar in composition and manufactured using the same process as commercial BioThrax vaccine. CPG 7909 is an immunostimulatory synthetic oligodeoxynucleotide that functions as an adjuvant.	Eligible participants randomized to receive BioThrax vaccine. BioThrax vaccine (Anthrax Vaccine Adsorbed; AVA) is licensed for post-exposure prophylaxis of anthrax disease.
Period Title: Overall Study
STARTED	1103	1103	1098	558
Received at Least One Study Vaccination	1100	1102	1097	558
Did Not Receive Any Study Vaccination	3	1	1	0
COMPLETED	1032	1026	1035	537
NOT COMPLETED	71	77	63	21

Baseline Characteristics

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3	BioThrax	Total
Arm/Group Description	Eligible participants randomized to receive AV7909 Lot 1.	Eligible participants randomized to receive AV7909 Lot 2.	Eligible participants randomized to receive AV7909 Lot 3.	Eligible participants randomized to receive BioThrax vaccine.	Total of all reporting groups
Overall Participants	1103	1103	1098	558	3862
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.0 (13.0)	39.2 (13.1)	38.9 (12.8)	38.6 (12.4)	39.0 (12.9)
Age, Customized (Count of Participants)
18-30 years	341 30.9%	355 32.2%	352 32.1%	176 31.5%	1224 31.7%
31-50 years	502 45.5%	470 42.6%	488 44.4%	269 48.2%	1729 44.8%
51-65 years	260 23.6%	278 25.2%	258 23.5%	113 20.3%	909 23.5%
Sex: Female, Male (Count of Participants)
Female	650 58.9%	615 55.8%	647 58.9%	308 55.2%	2220 57.5%
Male	453 41.1%	488 44.2%	451 41.1%	250 44.8%	1642 42.5%
Race/Ethnicity, Customized (Count of Participants)
Race : American Indian or Alaska Native	4 0.4%	4 0.4%	5 0.5%	2 0.4%	15 0.4%
Race : Asian	17 1.5%	18 1.6%	24 2.2%	15 2.7%	74 1.9%
Race : Black or African American	170 15.4%	186 16.9%	191 17.4%	89 15.9%	636 16.5%
Race : Native Hawaiian or Other Pacific Islander	2 0.2%	5 0.5%	3 0.3%	1 0.2%	11 0.3%
Race : White	878 79.6%	865 78.4%	852 77.6%	439 78.7%	3034 78.6%
Race : More than One Race	22 2%	20 1.8%	14 1.3%	9 1.6%	65 1.7%
Race : Other	8 0.7%	3 0.3%	5 0.5%	1 0.2%	17 0.4%
Race : Unknown	2 0.2%	2 0.2%	4 0.4%	2 0.4%	10 0.3%
Ethnicity: Not Hispanic or Latino	910 82.5%	938 85%	945 86.1%	450 80.6%	3243 84%
Ethnicity: Hispanic or Latino	177 16%	156 14.1%	142 12.9%	98 17.6%	573 14.8%
Ethnicity: Unknown	4 0.4%	2 0.2%	8 0.7%	4 0.7%	18 0.5%
Ethnicity: Not Reported	12 1.1%	7 0.6%	3 0.3%	6 1.1%	28 0.7%
Region of Enrollment (Count of Participants)
United States	1103 100%	1103 100%	1098 100%	558 100%	3862 100%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.9 (4.3)	27.3 (4.3)	27.2 (4.3)	27.3 (4.2)	27.1 (4.3)

Outcome Measures

1. Primary Outcome

Title	Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) 50% Neutralization Factor (NF50) at Day 64
Description	GMT of TNA NF50 at Day 64 in AV7909 study groups (Lots 1, 2 and 3) and BioThrax group. The outcome measure in AV7909 study groups was assessed for AV7909 lot-to-lot consistency, which was based on GMT TNA NF50 response at Day 64, wherein the 95% confidence interval (CI) for ratios of geometric mean titer (GMT) of TNA NF50 at Day 64 (seven weeks after second AV7909 vaccination) for each of the three AV7909 lot-to-lot comparisons had to be within equivalence margin of 0.5 and 2.0.
Time Frame	Day 64 (seven weeks after second AV7909 vaccination)

Outcome Measure Data

Analysis Population Description

Participants that met protocol-defined immunogenicity criteria from AV7909 Lot 1 group (n=878), AV7909 Lot 2 group (n=896), AV7909 Lot 3 group (n=896) and BioThrax group (n=454) are included.

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3	BioThrax
Arm/Group Description	Eligible participants who received AV7909 vaccine lot 1.	Eligible participants who received AV7909 vaccine lot 2.	Eligible participants who received AV7909 vaccine lot 3.	Eligible participants who received BioThrax vaccine.
Measure Participants	878	896	896	454
Geometric Mean (95% Confidence Interval) [Titer (TNA NF50)]	0.753	0.746	0.718	0.335

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AV7909 Lot 1, AV7909 Lot 2
	Comments
	Type of Statistical Test	Equivalence
	Comments	The 95% CIs for the Day 64 TNA NF50 GMT ratios between AV7909 Lot 1 and Lot 2 had to be within 0.5 to 2.0 equivalence margin.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AV7909 Lot 1, AV7909 Lot 3
	Comments
	Type of Statistical Test	Equivalence
	Comments	The 95% CIs for the Day 64 TNA NF50 GMT ratios between AV7909 Lot 1 and Lot 3 had to be within 0.5 to 2.0 equivalence margin.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	AV7909 Lot 2, AV7909 Lot 3
	Comments
	Type of Statistical Test	Equivalence
	Comments	The 95% CIs for the Day 64 TNA NF50 GMT ratios between AV7909 Lot 2 and Lot 3 had to be within 0.5 to 2.0 equivalence margin.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants in AV7909 Lot 1, Lot 2 and Lot 3 Groups Achieving a TNA NF50 ≥0.56 on Day 64
Description	Proportion of participants with TNA NF50 ≥0.56 at Day 64 in each AV7909 study groups (Lot 1, Lot 2, Lot 3). The assessment of the immune response in each study group was pre-defined as the lower bound of the two-sided 95% CI to be ≥40% for the percentage of AV7909 participants in each of the three lots achieving a TNA NF50 ≥0.56 at seven weeks after second AV7909 vaccination (Day 64).
Time Frame	Day 64 (seven weeks after second AV7909 vaccination)

Outcome Measure Data

Analysis Population Description

Data from participants that met protocol-defined criteria for inclusion in the immunogenicity population are included in the analysis; i.e., AV7909 Lot 1 n=878; AV7909 Lot 2 n=896; AV7909 Lot 3 n=896. Pre-defined success criteria (lower bound of the two-sided 95% CI to be ≥40% for the percentage of participants achieving a TNA NF50 ≥0.56 at Day 64) was only applicable for AV7909 study groups and not for BioThrax group; therefore, BioThrax group is not included.

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3
Arm/Group Description	Eligible participants who received AV7909 vaccine lot 1.	Eligible participants who received AV7909 vaccine lot 2.	Eligible participants who received AV7909 vaccine lot 3.
Measure Participants	878	896	896
Number (95% Confidence Interval) [percentage of participants]	68.5 6.2%	66.1 6%	64.5 5.9%

3. Primary Outcome

Title	Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.56 on Day 64
Description	Percentage of AV7909 participants (from all three AV7909 study groups pooled) achieving a TNA NF50 ≥0.56 on Day 64 (seven weeks after second AV7909 vaccination). The assessment of the immune response in AV7909 participants was pre-defined as the lower bound of the two-sided 95% CI for proportion of AV7909 participants with TNA NF50 ≥0.56 at Day 64 ≥40%.
Time Frame	Day 64 (seven weeks after second AV7909 vaccination)

Outcome Measure Data

Analysis Population Description

Data from participants who met protocol-defined criteria for inclusion in the immunogenicity population from all three AV7909 study groups (i.e., pooled AV7909; n=2670) were used for the analysis. The pre-defined success criteria (lower bound of the two-sided 95% CI to be ≥40% for the percentage of participants achieving a TNA NF50 ≥0.56 on Day 64) was not applicable for BioThrax participants, therefore BioThrax group was not included.

Arm/Group Title	Pooled AV7909
Arm/Group Description	Participants from groups 1-3 [.e., AV7909 Lot 1 (group 1), AV7909 Lot 2 (group 2) and AV7909 Lot 3 (group 3)] were pooled to assess TNA NF50 response at Day 64.
Measure Participants	2670
Number (95% Confidence Interval) [percentage of participants]	66.3 6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AV7909 Lot 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	66.3
	Confidence Interval	(2-Sided) 95%; 64.5 to 68.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Percentage of AV7909 Participants and BioThrax Participants With TNA NF50 ≥0.29 at Day 64
Description	Proportion of AV7909 participants (in each AV7909 study groups) and BioThrax participants who achieved TNA NF50 ≥0.29 at Day 64. Non-inferiority of AV7909 vaccine to BioThrax vaccine at Day 64 was assessed as determined by the two-sided lower bound for the 95% CI of the difference in the percentage of AV7909 participants (three lots pooled) with a TNA NF50 ≥0.29 and the percentage of BioThrax participants with a TNA NF50 ≥0.29 being greater than -15%.
Time Frame	Day 64 (seven weeks after second AV7909 vaccination; five weeks after third BioThrax vaccination)

Outcome Measure Data

Analysis Population Description

Data from participants who met protocol-defined criteria for inclusion in the immunogenicity population from each AV7909 study group (Lot 1 n=878; Lot 2 n=896; Lot 3 n=896) and BioThrax group (n=454) were used in the analysis. For the non-inferiority assessment, participants who met pre-defined criteria (achievement of TNA NF50 ≥0.29 at Day 64) from the pooled AV7909 study groups 1-3 (AV7909 Lot 1, Lot 2, Lot 3; i.e., Pooled AV7909) and BioThrax group were included.

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3	BioThrax
Arm/Group Description	Eligible participants who received AV7909 vaccine lot 1 and achieved TNA NF50 ≥0.29 at Day 64.	Eligible participants who received AV7909 vaccine lot 2 and achieved TNA NF50 ≥0.29 at Day 64.	Eligible participants who received AV7909 vaccine lot 3 and achieved TNA NF50 ≥0.29 at Day 64.	Eligible participants who received BioThrax vaccine and achieved TNA NF50 ≥0.29 at Day 64.
Measure Participants	878	896	896	454
Number (95% Confidence Interval) [percentage of participants]	86.9 7.9%	87.2 7.9%	85.8 7.8%	62.1 11.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AV7909 Lot 1, AV7909 Lot 2, AV7909 Lot 3, BioThrax
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	A non-inferiority margin of -15% was used for the difference in percentage of AV7909 participants (pooled from three AV7909 study groups [Lot 1, 2, and 3]) vs. BioThrax participants who achieved TNA NF50 ≥0.29 at Day 64. The success criterion was defined as the lower bound of 95% confidence interval of the difference in the percentage of AV7909 vs. BioThrax participants being greater than -15%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	24.5
	Confidence Interval	(2-Sided) 95%; 20.0 to 29.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Incidence of Serious Adverse Events
Description	Number of AV7909 participants or BioThrax participants who received at least one vaccination and reported serious adverse event(s) (SAEs) from the time of the first vaccination on Day 1 through Day 394.
Time Frame	Day 1 though Day 394

Outcome Measure Data

Analysis Population Description

For the relative risk of SAE incidence analysis, participants from all three AV7909 study groups (Lot 1, Lot 2, Lot 3) since AV7909 lots 1, 2 and 3 were considered the same product (consecutively manufactured, and released with the same product specifications); hence, it was pre-defined to combine SAE data from participants across the three AV7909 lots for SAE relative risk analysis.

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3	BioThrax
Arm/Group Description	Eligible participants who received at least one dose of AV7909 Lot 1.	Eligible participants who received at least one dose of AV7909 Lot 2.	Eligible participants who received at least one dose of AV7909 Lot 3.	Eligible participants who received at least one dose of BioThrax vaccine.
Measure Participants	1100	1102	1097	558
Count of Participants [Participants]	21 1.9%	16 1.5%	21 1.9%	4 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AV7909 Lot 1, AV7909 Lot 2, AV7909 Lot 3, BioThrax
	Comments
	Type of Statistical Test	Other
	Comments	Relative risk of serious adverse events incidence between AV7909 (combined from all three AV7909 lots) and BioThrax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk (AV7909/BioThrax)
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; 0.9 to 6.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI of the relative risk was derived using the Farrington-Manning relative risk score statistic.

6. Secondary Outcome

Title	Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.15 on Day 29.
Description	Proportion of AV7909 participants (in each AV7909 study group) who achieved TNA NF50 ≥0.15 at Day 29 (two weeks after second AV7909 vaccination). Assessment of the lower bound of the two-sided 95% CI to be ≥67% for the percentage of AV7909 participants in AV7909 study groups 1-3 (Pooled AV7909) achieving a TNA NF50 ≥0.15 on Day 29 was performed.
Time Frame	Day 29 (two weeks after second AV7909 vaccination)

Outcome Measure Data

Analysis Population Description

Data from participants who met protocol-defined criteria for inclusion in the immunogenicity population (AV7909 study groups 1-3) were used in the analysis. The pre-defined success criteria (lower bound of the two-sided 95% CI to be ≥67% for the percentage of participants achieving a TNA NF50 ≥0.15 on Day 29) was not applicable for BioThrax, therefore BioThrax group was not included.

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3
Arm/Group Description	Eligible participants who received AV7909 vaccine lot 1 and achieved TNA NF50 ≥0.15 at Day 29.	Eligible participants who received AV7909 vaccine lot 2 and achieved TNA NF50 ≥0.15 at Day 29.	Eligible participants who received AV7909 vaccine lot 3 and achieved TNA NF50 ≥0.15 at Day 29.
Measure Participants	863	878	876
Number (95% Confidence Interval) [percentage of participants]	98.1 8.9%	97.9 8.9%	97.4 8.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AV7909 Lot 1, AV7909 Lot 2, AV7909 Lot 3
	Comments
	Type of Statistical Test	Other
	Comments	Success criteria was defined as the lower bound for the 95% CI for the proportion of participants pooled from all three AV7909 study groups with TNA NF50 ≥0.15 to be ≥67%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	97.8
	Confidence Interval	(2-Sided) 95%; 97.2 to 98.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Incidence of Adverse Events
Description	Number of AV7909 or BioThrax participants who received at least one vaccination and had at least one adverse event reported from the time of the first vaccination on Day 1 through Day 64.
Time Frame	Day 1 through Day 64

Outcome Measure Data

Analysis Population Description

Data from participants who received at least one dose of AV7909 vaccine Lot 1 (n=1100), Lot 2 (n=1102) or Lot 3 (n=1097) or BioThrax vaccine (n=558) are included in the analysis.

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3	BioThrax
Arm/Group Description	Eligible participants who received at least one dose of AV7909 Lot 1.	Eligible participants who received at least one dose of AV7909 Lot 2.	Eligible participants who received at least one dose of AV7909 Lot 3.	Eligible participants randomized to receive BioThrax vaccine.
Measure Participants	1100	1102	1097	558
Count of Participants [Participants]	410 37.2%	400 36.3%	408 37.2%	210 37.6%

8. Secondary Outcome

Title	Incidence of Adverse Events of Special Interest (Events of Autoimmune Etiology)
Description	Incidence of adverse events of special interest (AESIs; events of autoimmune etiology) from the time of the first vaccination on Day 1 through Day 394 in participants who received at least one dose of AV7909 (Lot 1, Lot 2 or Lot 3) or BioThrax vaccines.
Time Frame	Day 1 through Day 394

Outcome Measure Data

Analysis Population Description

Data from participants who received at least one dose of AV7909 vaccine (Lot 1, Lot 2 or Lot 3) or BioThrax vaccine are used in the analysis. Since AV7909 lots 1, 2 and 3 were considered the same product (consecutively manufactured, and released with the same product specifications), it was pre-defined to combine AESI data from participants across the three AV7909 lots for AESI relative risk analysis.

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3	BioThrax
Arm/Group Description	Eligible participants who received at least one dose of AV7909 Lot 1.	Eligible participants who received at least one dose of AV7909 Lot 2.	Eligible participants who received at least one dose of AV7909 Lot 3.	Eligible participants randomized to receive BioThrax vaccine.
Measure Participants	1100	1102	1097	558
Count of Participants [Participants]	5 0.5%	4 0.4%	6 0.5%	2 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AV7909 Lot 1, AV7909 Lot 2, AV7909 Lot 3, BioThrax
	Comments
	Type of Statistical Test	Other
	Comments	Relative risk of adverse events of special interest (events of autoimmune etiology) incidence between AV7909 (combined from all three AV7909 lots) and BioThrax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk (AV7909/BioThrax)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; 0.3 to 5.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI of the relative risk was derived using the Farrington-Manning relative risk score statistic.

9. Secondary Outcome

Title	Incidence of Solicited Systemic Reactogenicity Events
Description	Incidence of any solicited systemic reactogenicity reaction after any AV7909 or BioThrax vaccination.
Time Frame	Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day)

Outcome Measure Data

Analysis Population Description

Data from participants (solicited systemic reactogenicity events after any vaccination) who received at least one dose of AV7909 vaccine or BioThrax vaccine are included in the analysis.

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3	BioThrax
Arm/Group Description	Eligible participants who received at least one dose of AV7909 Lot 1.	Eligible participants who received at least one dose of AV7909 Lot 2.	Eligible participants who received at least one dose of AV7909 Lot 3.	Eligible participants randomized to receive BioThrax vaccine.
Measure Participants	1100	1102	1097	558
Count of Participants [Participants]	930 84.3%	923 83.7%	906 82.5%	438 78.5%

10. Secondary Outcome

Title	Incidences of Solicited Injection Site Reactogenicity Events
Description	Incidence of any solicited injection site reactogenicity reaction after any AV7909 (Lots 1, 2 or 3) or BioThrax vaccination.
Time Frame	Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day)

Outcome Measure Data

Analysis Population Description

Data from participants who received at least one dose of AV7909 or BioThrax dose are included in the analysis.

Arm/Group Title	AV7909 Lot 1	AV7909 Lot 2	AV7909 Lot 3	BioThrax
Arm/Group Description	Eligible participants who received at least one dose of AV7909 Lot 1.	Eligible participants who received at least one dose of AV7909 Lot 2.	Eligible participants who received at least one dose of AV7909 Lot 3.	Eligible participants randomized to receive BioThrax vaccine.
Measure Participants	1100	1102	1097	558
Count of Participants [Participants]	1009 91.5%	1010 91.6%	1013 92.3%	525 94.1%

Adverse Events

Time Frame	Day 1 through Day 394.
Adverse Event Reporting Description	Adverse events, serious adverse events and adverse events of special interest (events of autoimmune etiology) were collected from Day 1 through Day 394. Local and systemic reactogenicity were solicited for seven days after each vaccination.
Arm/Group Title	AV7909 Lot 1		AV7909 Lot 2		AV7909 Lot 3		BioThrax
Arm/Group Description	Eligible participants who received at least one dose of AV7909 Lot 1.		Eligible participants who received at least one dose of AV7909 Lot 2.		Eligible participants who received at least one dose of AV7909 Lot 3.		Eligible participants who received at least one dose of BioThrax vaccine.
All Cause Mortality
	AV7909 Lot 1		AV7909 Lot 2		AV7909 Lot 3		BioThrax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/1100 (0.2%)		2/1102 (0.2%)		2/1097 (0.2%)		0/558 (0%)
Serious Adverse Events
	AV7909 Lot 1		AV7909 Lot 2		AV7909 Lot 3		BioThrax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/1100 (1.9%)		16/1102 (1.5%)		21/1097 (1.9%)		4/558 (0.7%)
Blood and lymphatic system disorders
Lymphadenitis	0/1100 (0%)	0	0/1102 (0%)	0	0/1097 (0%)	0	1/558 (0.2%)	1
Cardiac disorders
Acute myocardial infarction	0/1100 (0%)	0	1/1102 (0.1%)	2	0/1097 (0%)	0	0/558 (0%)	0
Atrial flutter	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Coronary artery disease	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Myocardial infarction	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Colitis	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Haematemesis	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Pancreatitis acute	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Rectal prolapse	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Small intestinal obstruction	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
General disorders
Death	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Gait disturbance	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Non-cardiac chest pain	0/1100 (0%)	0	1/1102 (0.1%)	3	0/1097 (0%)	0	0/558 (0%)	0
Treatment noncompliance	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Cholecystitis acute	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Infections and infestations
Appendicitis	1/1100 (0.1%)	1	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Abdominal abscess	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Cellulitis	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Corona virus infection	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Pneumonia	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	1/558 (0.2%)	1
Pyelonephritis	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Sepsis	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Vulval abscess	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Sialoadenitis	0/1100 (0%)	0	0/1102 (0%)	0	0/1097 (0%)	0	1/558 (0.2%)	1
Injury, poisoning and procedural complications
Toxicity to various agents	1/1100 (0.1%)	1	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Ankle fracture	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Eye injury	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Gun shot wound	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Joint injury	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Lower limb fracture	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Multiple fractures	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Multiple injuries	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Overdose	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Radius fracture	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Rib fracture	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Skin laceration	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis	0/1100 (0%)	0	0/1102 (0%)	0	2/1097 (0.2%)	2	0/558 (0%)	0
Intervertebral disc protrusion	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Mobility decreased	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Musculoskeletal chest pain	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Systemic lupus erythematosus	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer	1/1100 (0.1%)	1	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Colon cancer metastatic	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Intraductal proliferative breast lesion	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Invasive ductal breast carcinoma	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Rectal cancer	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Uterine leiomyoma	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Nervous system disorders
Headache	0/1100 (0%)	0	1/1102 (0.1%)	1	1/1097 (0.1%)	1	0/558 (0%)	0
Syncope	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Toxic encephalopathy	1/1100 (0.1%)	1	0/1102 (0%)	0	0/1097 (0%)	0	0/558 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	3/1100 (0.3%)	3	2/1102 (0.2%)	2	0/1097 (0%)	0	1/558 (0.2%)	1
Abortion missed	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Premature rupture of membranes	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Psychiatric disorders
Completed suicide	0/1100 (0%)	0	2/1102 (0.2%)	2	0/1097 (0%)	0	0/558 (0%)	0
Anxiety	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Dysphemia	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Post-traumatic stress disorder	0/1100 (0%)	0	1/1102 (0.1%)	1	0/1097 (0%)	0	0/558 (0%)	0
Reproductive system and breast disorders
Uterine haemorrhage	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/1100 (0%)	0	0/1102 (0%)	0	1/1097 (0.1%)	1	0/558 (0%)	0
Vascular disorders	0/1100 (0%)	0	0/1102 (0%)	0	0/1097 (0%)	0	1/558 (0.2%)	1
Thrombosis	0/1100 (0%)	0	0/1102 (0%)	0	0/1097 (0%)	0	1/558 (0.2%)	1
Other (Not Including Serious) Adverse Events
	AV7909 Lot 1		AV7909 Lot 2		AV7909 Lot 3		BioThrax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	193/1100 (17.5%)		189/1102 (17.2%)		120/1097 (10.9%)		110/558 (19.7%)
Gastrointestinal disorders
Diarrhoea	10/1100 (0.9%)	10	5/1102 (0.5%)	6	7/1097 (0.6%)	8	6/558 (1.1%)	6
General disorders
Injection site pain	32/1100 (2.9%)	57	35/1102 (3.2%)	57	29/1097 (2.6%)	54	13/558 (2.3%)	32
Injection site erythema	5/1100 (0.5%)	6	8/1102 (0.7%)	8	16/1097 (1.5%)	16	9/558 (1.6%)	9
Injection site induration	10/1100 (0.9%)	11	11/1102 (1%)	11	8/1097 (0.7%)	9	54/558 (9.7%)	69
Injection site swelling	5/1100 (0.5%)	6	5/1102 (0.5%)	5	8/1097 (0.7%)	9	15/558 (2.7%)	16
Injection site warmth	5/1100 (0.5%)	6	2/1102 (0.2%)	3	5/1097 (0.5%)	5	7/558 (1.3%)	8
Injection site bruising	5/1100 (0.5%)	6	5/1102 (0.5%)	5	1/1097 (0.1%)	1	9/558 (1.6%)	10
Injection site pruritus	4/1100 (0.4%)	5	2/1102 (0.2%)	3	3/1097 (0.3%)	3	13/558 (2.3%)	14
Injection site mass	1/1100 (0.1%)	1	2/1102 (0.2%)	2	0/1097 (0%)	0	8/558 (1.4%)	10
Infections and infestations
Upper respiratory tract infection	27/1100 (2.5%)	30	34/1102 (3.1%)	36	31/1097 (2.8%)	34	12/558 (2.2%)	14
Urinary tract infection	18/1100 (1.6%)	21	13/1102 (1.2%)	18	21/1097 (1.9%)	23	4/558 (0.7%)	4
Nasopharyngitis	12/1100 (1.1%)	12	8/1102 (0.7%)	8	10/1097 (0.9%)	10	6/558 (1.1%)	7
Influenza	8/1100 (0.7%)	8	6/1102 (0.5%)	6	7/1097 (0.6%)	7	6/558 (1.1%)	6
Injury, poisoning and procedural complications
Vaccination complication	27/1100 (2.5%)	29	31/1102 (2.8%)	33	28/1097 (2.6%)	31	7/558 (1.3%)	8
Procedural headache	20/1100 (1.8%)	21	26/1102 (2.4%)	27	31/1097 (2.8%)	34	12/558 (2.2%)	14
Musculoskeletal procedural complication	14/1100 (1.3%)	14	21/1102 (1.9%)	21	26/1097 (2.4%)	28	4/558 (0.7%)	4
Musculoskeletal and connective tissue disorders
Back pain	18/1100 (1.6%)	20	10/1102 (0.9%)	10	9/1097 (0.8%)	9	6/558 (1.1%)	6
Nervous system disorders
Headache	16/1100 (1.5%)	17	15/1102 (1.4%)	17	14/1097 (1.3%)	15	7/558 (1.3%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.