Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AV7909 · 3 trials · 1 indication
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.
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).
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%.
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%.
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.
Based on serum concentrations of ciprofloxacin on Day 8 (pre-AV7909 vaccination) and on Day 35 (post-AV7909 vaccination), steady state AUC0-12h and Cmax were derived, and geometric mean of ratio of AUC0-12h on Day35/Day 8 and geometric mean of ratio for Cmax on Day 35/Day8, and the corresponding 90% CI of the mean ratios were calculated.
Based on serum concentrations of doxycycline on Day 8 (pre-AV7909 vaccination) and on Day 38 (post-AV7909 vaccination), steady state AUC0-12h and Cmax were derived, and geometric mean of ratio of AUC0-12h on Day38/Day 8 and geometric mean of ratio for Cmax on Day 38/Day8, and the corresponding 90% CI of the mean ratios were calculated.
Immunogenicity measured by the lower bound (LB) of the 95% confidence intervals (CIs) for the proportion of subjects in each study arm with Day 63 TNA 50% neutralization factor (NF50) values greater than or equal to threshold
Incidence of adverse events (including assessment of symptoms, physical exam findings, clinical laboratory tests, and vital signs) from the time of the first immunization on Day 0 through Day 84
Incidence of solicited systemic reactions and solicited injection site reactions each day for 7 days following each vaccination using subject e-diaries by severity. Reactions were graded using the following scale (note, for redness and swelling, the diameter \[greater of two perpendicular measurements\] was assessed by the subject using an injection site measurement tool): Grade 0 (Absent): Symptom not present; Grade 1 (Mild): Symptom present but does not interfere with activities of daily living, or affected area (redness, swelling) measures \<3 cm; Grade 2 (Moderate): Symptom causes some interference with activities of daily living, or affected area (redness, swelling) measures 3 - 10 cm; Grade 3 (Severe): Symptom prevents activities of daily living or requires treatment, or affected area (redness, swelling) measures \> 10 cm. For each reaction, subjects are counted once across all vaccinations at the highest reported level of severity.
Incidence of clinical laboratory abnormalities throughout the study (up to Day 84). Clinical laboratory abnormalities are presented as the total of Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (potentially life-threatening) abnormalities according to criteria adapted from the U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research: Guidance for Industry. Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007). Within each laboratory parameter, subjects are counted once for their most severe occurrence of clinical laboratory abnormality.
Incidence of immunologically significant adverse events of special interest as defined by the Center for Biologics Evaluation and Research from the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination
| Arm | Type | Description |
|---|---|---|
| AV7909 Lot 1 | EXPERIMENTAL | 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. |
| AV7909 Lot 2 | EXPERIMENTAL | 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. |
| AV7909 Lot 3 | EXPERIMENTAL | 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. |
| BioThrax | ACTIVE_COMPARATOR | 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. |
| Group 1:Ciprofloxacin + AV7909 | EXPERIMENTAL | Participants meeting entry criteria will be randomized 1:1:1 to one of three investigational study groups. Groups 1 to 3 will each receive a manufactured lot of AV7909 per the study visit schedule. Group 1 will concomitantly receive ciprofloxacin. |
| Group 2: Doxycycline +AV7909 | EXPERIMENTAL | Participants meeting entry criteria will be randomized 1:1:1 to one of three investigational study groups. Groups 1 to 3 will each receive a manufactured lot of AV7909 per the study visit schedule. Group 2 will concomitantly receive doxycycline. |
| Group 3: AV7909 | EXPERIMENTAL | Participants meeting entry criteria will be randomized 1:1:1 to one of three investigational study groups. Groups 1 to 3 will each receive a manufactured lot of AV7909 per the study visit schedule. |
| AV7909 (Day 0 and 14) | EXPERIMENTAL | Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 |
| AV7909 (Day 0 and 28) | EXPERIMENTAL | Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 |
| AV7909 (Day 0, 14, and 28) | EXPERIMENTAL | Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 |
| AV7909 Reduced Dose | EXPERIMENTAL | Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 |
| Name | Type | Description |
|---|---|---|
| AV7909 | BIOLOGICAL | 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. |
| BioThrax | BIOLOGICAL | BioThrax vaccine (Anthrax Vaccine Adsorbed; AVA) is licensed for post-exposure prophylaxis of anthrax disease. |
| Ciprofloxacin 500Mg Tablet | DRUG | Ciprofloxacin 500mg administered by mouth every 12 hours. The antibiotic will be administered orally on Study Days 4-9, 22-24 and 31-37. |
| Doxycycline 100Mg Tablet | DRUG | Doxycycline 100mg administered by mouth every 12 hours. The antibiotic will be administered orally on Study Days 2-9, 22-24 and 32-38. |
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. B...
AV7909 is an investigational vaccine being developed for the prevention of anthrax, a serious infectious disease caused by Bacillus anthracis. It is currently in clinical development and has not been approved by the FDA. The vaccine is being studied in healthy adults aged 18 years and older in the United States.
AV7909 is being developed by Emergent BioSolutions Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker symbol EBS. The company is conducting clinical trials to evaluate the safety and immunogenicity of the vaccine for anthrax prevention.
AV7909 is in Phase 3 clinical development. The most advanced trial, VELOCITY (NCT03877926), is a Phase 3 study that has been completed. The vaccine is investigational and has not received FDA approval. It is being studied for the prevention of anthrax.
AV7909 has been studied in three completed clinical trials: NCT01770743, a Phase 2 safety and immunogenicity study with 168 participants; NCT03877926 (VELOCITY), a Phase 3 study with 3,689 participants; and NCT04067011 (Velocity 2), a Phase 2 study with 210 participants. All trials were conducted in the United States.
AV7909 is a distinct investigational anthrax vaccine being developed by Emergent BioSolutions. It is not the same as other approved anthrax vaccines. The vaccine is being evaluated in clinical trials to determine its safety and ability to generate an immune response against anthrax.