Safety, Tolerability and Immunogenicity Study of AV7909 Anthrax Vaccine in Healthy Adults

NCT01263691 | Completed Phase 1 Results DMC

• 2 other identifiers: EBS.AVA.201 / DMID 10-0013HHSN272200800051C
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this Phase 1 clinical trial is to evaluate the safety, tolerability, and immunogenicity of AV7909 anthrax vaccine in healthy adults. In this study, healthy male and female subjects between 18 and 50 years of age will receive vaccinations via the intramuscular (IM) route at Days 0 and 14. Safety and tolerability will be evaluated via laboratory tests, physical examinations, vital signs, adverse events (AEs), concomitant medications, and local and systemic signs and symptoms of reactogenicity.

Conditions

Bacillus Anthracis (Anthrax) Infection

Keywords

AVA; AV7909; Anthrax vaccine

Outcome Measures

Primary Outcomes (10)

• Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Vaccination (Day 0)

  Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the first injection (Day 0). All local reactions collected by subjects on diary cards were recorded as adverse events. Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials." Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows: * Grade 0: none * Grade 1: \<3 cm * Grade 2: 3 to 10 cm * Grade 3: \>10 cm For all other ISRs, the following scale was used: * Grade 0: not present * Grade 1: present with no limitation of activity * Grade 2: interfering with daily activities or requiring non-narcotic treatment * Grade 3: preventing normal daily activities or requiring narcotic analgesia

  Days 0-6

• Percentage of Subjects With Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Vaccination (Day 0)

  Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the first injection (Day 0). All local reactions collected by subjects on diary cards were recorded as adverse events. Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials." Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows: * Grade 0: none * Grade 1: \<3 cm * Grade 2: 3 to 10 cm * Grade 3: \>10 cm For all other ISRs, the following scale was used: * Grade 0: not present * Grade 1: present with no limitation of activity * Grade 2: interfering with daily activities or requiring non-narcotic treatment * Grade 3: preventing normal daily activities or requiring narcotic analgesia

  Days 0-6

• Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Vaccination (Day 14)

  Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the second injection (Day 14). All local reactions collected by subjects on diary cards were recorded as adverse events. Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials." Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows: * Grade 0: none * Grade 1: \<3 cm * Grade 2: 3 to 10 cm * Grade 3: \>10 cm For all other ISRs, the following scale was used: * Grade 0: not present * Grade 1: present with no limitation of activity * Grade 2: interfering with daily activities or requiring non-narcotic treatment * Grade 3: preventing normal daily activities or requiring narcotic analgesia

  Days 14-20

• Percentage of Subjects With Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Vaccination (Day 14)

  Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the second injection (Day 14). All local reactions collected by subjects on diary cards were recorded as adverse events. Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials." Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows: * Grade 0: none * Grade 1: \<3 cm * Grade 2: 3 to 10 cm * Grade 3: \>10 cm For all other ISRs, the following scale was used: * Grade 0: not present * Grade 1: present with no limitation of activity * Grade 2: interfering with daily activities or requiring non-narcotic treatment * Grade 3: preventing normal daily activities or requiring narcotic analgesia

  Days 14-20

• Incidence of Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Injection (Day 0)

  Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events. Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials." Toxicity grades for fever were derived from body temperature using the following scale: * Grade 0: \<100°F * Grade 1: 100.0 - 101.5°F * Grade 2: 101.6 - 102.9°F ; * Grade 3: 103.0 - 105.0°F For all other systemic reactions, the following scale was used: * Grade 0: not present * Grade 1: present with no limitation of activity * Grade 2: interfering with daily activities or requiring non-narcotic treatment * Grade 3: preventing normal daily activities or requiring narcotic analgesia

  Days 0-6

• Percentage of Subjects With Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Injection (Day 0)

  Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events. Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials." Toxicity grades for fever were derived from body temperature using the following scale: * Grade 0: \<100°F * Grade 1: 100.0 - 101.5°F * Grade 2: 101.6 - 102.9°F ; * Grade 3: 103.0 - 105.0°F For all other systemic reactions, the following scale was used: * Grade 0: not present * Grade 1: present with no limitation of activity * Grade 2: interfering with daily activities or requiring non-narcotic treatment * Grade 3: preventing normal daily activities or requiring narcotic analgesia

  Days 0-6

• Incidence of Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Injection (Day 14)

  Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events. Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials." Toxicity grades for fever were derived from body temperature using the following scale: * Grade 0: \<100°F * Grade 1: 100.0 - 101.5°F * Grade 2: 101.6 - 102.9°F ; * Grade 3: 103.0 - 105.0°F For all other systemic reactions, the following scale was used: * Grade 0: not present * Grade 1: present with no limitation of activity * Grade 2: interfering with daily activities or requiring non-narcotic treatment * Grade 3: preventing normal daily activities or requiring narcotic analgesia

  Days 14-20

• Percentage of Subjects With Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Injection (Day 14)

  Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events. Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials." Toxicity grades for fever were derived from body temperature using the following scale: * Grade 0: \<100°F * Grade 1: 100.0 - 101.5°F * Grade 2: 101.6 - 102.9°F ; * Grade 3: 103.0 - 105.0°F For all other systemic reactions, the following scale was used: * Grade 0: not present * Grade 1: present with no limitation of activity * Grade 2: interfering with daily activities or requiring non-narcotic treatment * Grade 3: preventing normal daily activities or requiring narcotic analgesia

  Days 14-20

• Incidence of Hematology, Serum Chemistry, and Urinalysis Abnormalities Reported as Adverse Events

  Hematology test included hemoglobin, hematocrit, white blood cell count, absolute lymphocyte count, absolute neutrophil count, absolute eosinophil count, and platelet count. Serum chemistry test included albumin, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, glucose, calcium, potassium, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Urinalysis included appearance, color, pH, specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and occult blood. Hematology tests were done on Days 0, 1, 2, 7, 28, and 56. Serum chemistry tests and urinalysis were done on Days 0, 7, 28, and 56.

  Days 0-56

• Percentage of Subjects With Hematology, Serum Chemistry, and Urinalysis Abnormalities Reported as Adverse Events

  Hematology test included hemoglobin, hematocrit, white blood cell count, absolute lymphocyte count, absolute neutrophil count, absolute eosinophil count, and platelet count. Serum chemistry test included albumin, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, glucose, calcium, potassium, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Urinalysis included appearance, color, pH, specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and occult blood. Hematology tests were done on Days 0, 1, 2, 7, 28, and 56. Serum chemistry tests and urinalysis were done on Days 0, 7, 28, and 56.

  Days 0-56

Secondary Outcomes (3)

• Peak TNA NF50 GMT for All Subjects in the Immunogenicity Population and by Gender After IM Administration of Investigational Product on Days 0 and 14.

  Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.

• Median Time to Peak TNA NF50 GMT for All Subjects in the Immunogenicity Population and by Gender After IM Administration of Investigational Product on Days 0 and 14.

  Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.

• TNA NF50 GMTs Across Study Days After IM Administration of Investigational Product on Days 0 and 14.

  Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.

Study Arms (6)

BioThrax

ACTIVE COMPARATOR

BioThrax, 0.5 mL AVA per dose

Biological: BioThrax

AV7909 Formulation 1

EXPERIMENTAL

0.5 mL AVA + 0.5 mg CPG 7909 per 0.5 mL dose

Biological: AV7909 Formulation 1

AV7909 Formulation 2

EXPERIMENTAL

0.5 mL AVA + 0.25 mg CPG 7909 per 0.5 mL dose

Biological: AV7909 Formulation 2

AV7909 Formulation 3

EXPERIMENTAL

0.25 mL AVA + 0.5 mg CPG 7909 per 0.5 mL dose

Biological: AV7909 Formulation 3

AV7909 Formulation 4

EXPERIMENTAL

0.25 mL AVA + 0.25 mg CPG 7909 per 0.5 mL dose

Biological: AV7909 Formulation 4

Control

PLACEBO COMPARATOR

Saline control

Drug: Control

Interventions

BioThrax BIOLOGICAL

BioThrax

Also known as: Anthrax Vaccine Adsorbed (AVA)

BioThrax

AV7909 Formulation 1 BIOLOGICAL

AV7909 Formulation 1

AV7909 Formulation 1

AV7909 Formulation 2 BIOLOGICAL

AV7909 Formulation 2

AV7909 Formulation 2

AV7909 Formulation 3 BIOLOGICAL

AV7909 Formulation 3

AV7909 Formulation 3

AV7909 Formulation 4 BIOLOGICAL

AV7909 Formulation 4

AV7909 Formulation 4

Control DRUG

Saline control

Control

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be between 18 and 50 years of age, inclusive, at the time of enrollment.
• Be in good health as determined by the investigator from medical history and a physical examination.
• If a pre-menopausal female, must be using acceptable methods of birth control.
• Have all hematology and chemistry parameters (measured at Screening) within the laboratory's normal range.
• Have negative values for the following tests at Screening: Hepatitis C antibody, anti-Human Immunodeficiency Virus (Anti-HIV-1/-2/-O), and anti-Hepatitis B Core Antigen (Anti-HBc).
• Be willing and capable of complying with all aspects of the protocol through completion of the required visits.
• Have not donated blood in the preceding 8 weeks and are willing to not donate blood or plasma within 56 days after dosing.
• Have adequate venous access for repeat phlebotomies.
• Have read, understood and signed an informed consent form.

You may not qualify if:

• A known anaphylactic response, severe systematic response, or serious hypersensitivity reaction to a prior immunization.
• Prior immunization with anthrax vaccine, recombinant Protective Antigen (rPA) vaccine, or known exposure to anthrax organisms.
• Have previously served in the military or plans to enlist in the military from Screening through Day 84.
• Have participated in anthrax therapeutic or vaccine trials (monoclonal anti-protective antigen (PA) or anthrax immune globulins or anthrax vaccines).
• Participation in any investigational clinical trial within 30 days preceding the Screening visit or planning to participate in a clinical trial requiring dosing through the Day 194 visit.
• A history of drug or alcohol abuse within 12 months prior to Screening, or a positive result on a urine drug screen for amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, methylenedioxymethamphetamine opiates, oxycodone, phencyclidine, propoxyphene, or tricyclic antidepressants.
• Blood pressure greater than 145 millimeters of mercury (mmHg) systolic or 90 mmHg diastolic.
• Past history of significant autoimmune disease such as rheumatoid arthritis, lupus erythematous, psoriasis, glomerulonephritis, or autoimmune thyroiditis.
• A medical condition that, in the opinion of the Principal Investigator (PI), could adversely impact the subject's participation, safety, or conduct of the study.

Sponsors & Collaborators

• Emergent BioSolutions: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Department of Health and Human Services: collaborator

Study Sites (3)

Miami Research Associates

Miami, Florida, 33143, United States

Location

North Carolina Clinical Research

Raleigh, North Carolina, 27607, United States

Location

Jean Brown Research

Salt Lake City, Utah, 84124, United States

Location

Related Publications (1)

• Hopkins RJ, Daczkowski NF, Kaptur PE, Muse D, Sheldon E, LaForce C, Sari S, Rudge TL, Bernton E. Randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers. Vaccine. 2013 Jun 26;31(30):3051-8. doi: 10.1016/j.vaccine.2013.04.063. Epub 2013 May 10.

  PMID: 23701746 RESULT

MeSH Terms

Conditions

Anthrax; Infections

Interventions

Biothrax; Anthrax Vaccines

Condition Hierarchy (Ancestors)

Bacillaceae Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr. Robert Hopkins
• Organization: Emergent BioSolutions

hopkinsr@ebsi.com

(301) 944-0136

Study Officials

• Edward Bernton, MD

  Emergent Biosolutions, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2010
• First Posted: December 21, 2010
• Study Start: December 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: June 1, 2012
• Last Updated: March 18, 2024
• Results First Posted: August 20, 2014

Record last verified: 2024-03

Locations

US (3)