Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Anthrax vaccine adsorbed (BioThrax), BioThrax, Anthrax Vaccine Adsorbed
AVA · 4 trials · 3 indications
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.
Ratios of Area Under the Curve from zero to 12 hours (AUC0-12h) and maximum concentration (Cmax) achieved for ciprofloxacin (Day 5/Day 44).
Safety will be measured by looking at safety labs, Adverse Events (AEs) and vaccine reactogenicity data from Baseline through Day 211. Immunogenicity will be measured by the peak serum antibody response to the PA transgene defined as the highest toxin-neutralizing antibody (TNA) titer achieved by a subject at any time between the first post-vaccination visit though Day 85 (and Day 211 if Day 85 is positive).
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
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
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
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
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
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
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
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
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.
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.
| Arm | Type | Description |
|---|---|---|
| BioThrax (0.5 mL, on days 0, 14, and 28) | EXPERIMENTAL | - |
| BioThrax + Ciprofloxacin PK | EXPERIMENTAL | BioThrax: route of administration/schedule- 0.5 mL subcutaneous (SC) injection / 0-2-4 week schedule. Ciprofloxacin: 500 mg twice a day (Days 1-6, 19-21, 33-35, 40-48). |
| BioThrax + Ciprofloxacin no PK | EXPERIMENTAL | BioThrax: route of administration/schedule- 0.5 mL subcutaneous (SC) injection / 0-2-4 week schedule. Ciprofloxacin: 500 mg twice a day (Days 1-6, 19-21, 33-35, 40-48). |
| BioThrax only | EXPERIMENTAL | BioThrax: route of administration/schedule- 0.5 mL subcutaneous (SC) injection / 0-2-4 week schedule. |
| AVA | ACTIVE_COMPARATOR | Anthrax Vaccine Adsorbed (0.5 mL) as the placebo control on Days 1, 15 and 29 |
| Ad4-PA-1 | EXPERIMENTAL | Given at 10\^9, 10\^10 and 10\^11 vp Ad4-PA at Day 1 + oral placebo on Day 15 + AVA boost at Day 29 |
| Ad4-PA-2 | EXPERIMENTAL | Given at 10\^9, 10\^10 and 10\^11 vp Ad4-PA at Days 1, 15 and 29 |
| Ad4-PA-3 | EXPERIMENTAL | Ad4 given at 10\^9, 10\^10 and 10\^11 vp Ad4 PA-GPI at Day 1 + AVA boost at Day 15 + placebo on Day 29 |
| Ad4-PA-GPI-1 | EXPERIMENTAL | Given at 10\^9, 10\^10 and 10\^11 viral particles Ad4 PA-GPI at Day 1 + oral placebo on Day 29 + AVA boost at Day 15 |
| Ad4 PA-GPI-2 | EXPERIMENTAL | Given at 10\^9, 10\^10 and 10\^11 viral particles Ad4 PA-GPI at Day 1 + placebo on Day 15 + AVA boost at Day 29 |
| Ad4-PA-GPI -3 | EXPERIMENTAL | Given at 10\^9, 10\^10 and 10\^11 viral particles Ad4-PA-GPI at Days 1, 15 and 29 |
| BioThrax | ACTIVE_COMPARATOR | BioThrax, 0.5 mL AVA per dose |
| AV7909 Formulation 1 | EXPERIMENTAL | 0.5 mL AVA + 0.5 mg CPG 7909 per 0.5 mL dose |
| AV7909 Formulation 2 | EXPERIMENTAL | 0.5 mL AVA + 0.25 mg CPG 7909 per 0.5 mL dose |
| AV7909 Formulation 3 | EXPERIMENTAL | 0.25 mL AVA + 0.5 mg CPG 7909 per 0.5 mL dose |
| AV7909 Formulation 4 | EXPERIMENTAL | 0.25 mL AVA + 0.25 mg CPG 7909 per 0.5 mL dose |
| Control | PLACEBO_COMPARATOR | Saline control |
| Name | Type | Description |
|---|---|---|
| BioThrax | BIOLOGICAL | BioThrax, 0.5 mL administered subcutaneously on days 0, 14, and 28. |
| Ciprofloxacin | DRUG | 500 mg twice a day (Days 1-6, 19-21, 33-35, 40-48). |
| AVA | BIOLOGICAL | Anthrax Vaccine Adsorbed (0.5 mL) as the placebo control on Days 1, 15 and 29 |
| Ad4-PA-1 | BIOLOGICAL | Ad4-PA will be given at 10\^9, 10\^10 and 10\^11 on Day, followed by an oral placebo on Day 15 and an AVA boost on Day 29 |
| Ad4-PA-GPI-1 | BIOLOGICAL | Given at 10\^9, 10\^10 and 10\^11 viral particles Ad4 PA-GPI at Day 1 + oral placebo on Day 29 + AVA boost at Day 15 |
| AV7909 Formulation 1 | BIOLOGICAL | AV7909 Formulation 1 |
| AV7909 Formulation 2 | BIOLOGICAL | AV7909 Formulation 2 |
| AV7909 Formulation 3 | BIOLOGICAL | AV7909 Formulation 3 |
| AV7909 Formulation 4 | BIOLOGICAL | AV7909 Formulation 4 |
| Control | DRUG | Saline control |
Inclusion Criteria: * Be between 18 and 65 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 hematolog...
AVA is an investigational monoclonal antibody being developed for the prevention or treatment of anthrax infection. It is currently in Phase 1 clinical development and has not been approved by regulatory authorities.
AVA is being developed by Emergent BioSolutions Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker symbol EBS.
AVA is in Phase 1 clinical development. A Phase 1 ascending dose study has been completed, but the drug remains investigational and has not received regulatory approval.
AVA has been studied in one completed Phase 1 trial, NCT01979406, which assessed the safety and immunogenicity of adenovirus anthrax vector candidate vaccines. The trial enrolled 120 healthy volunteers in the United States.
AVA is a monoclonal antibody candidate for anthrax infection, distinct from traditional vaccines. The completed trial NCT01979406 evaluated adenovirus-based vector candidate vaccines, and AVA is being developed as a separate therapeutic approach.