VELOCITY: An Anthrax Vaccine Clinical Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Anthrax

Intervention / Treatment
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* Biological: AV7909
* Biological: BioThrax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained from the participant (dated and signed). Healthy condition as established by medical history and clinical examination before entering into the study. A male or female aged 18 to 65 years, inclusive, at the time of informed consent. Body mass index (BMI) ≤35.0 kg/m^2 at Screening visit. Have adequate venous access for phlebotomies. 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: 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. 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. 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. Planned administration of any commercially-available vaccine from seven days prior to the first study vaccination through two weeks after the last vaccination. 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. History of anthrax disease, suspected exposure to anthrax, or previous vaccination with any anthrax vaccine. Have a tattoo/scar/birthmark or any other skin condition affecting the deltoid area that may interfere with injection site assessments. A positive blood test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) HIV-1 or HIV-2 antibodies. Any confirmed or suspected immunodeficiency condition (congenital or secondary) or autoimmune disease based on medical history and Physical Exam, for example, Guillain-Barré. A family history of congenital or hereditary immunodeficiency. 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). 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. Any medical condition that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study. Any planned elective surgery during the study through 12 months after the last vaccination. 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. 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. Member or family member of the investigator site team. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AV7909 Lot 1<br>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<br>* 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.<br>|
| Experimental: AV7909 Lot 2<br>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<br>* 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.<br>|
| Experimental: AV7909 Lot 3<br>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<br>* 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.<br>|
| Active Comparator: BioThrax<br>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<br>* BioThrax vaccine (Anthrax Vaccine Adsorbed; AVA) is licensed for post-exposure prophylaxis of anthrax disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) 50% Neutralization Factor (NF50) at Day 64 | 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. | Day 64 (seven weeks after second AV7909 vaccination) | 
| Percentage of Participants in AV7909 Lot 1, Lot 2 and Lot 3 Groups Achieving a TNA NF50 ≥0.56 on Day 64 | 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). | Day 64 (seven weeks after second AV7909 vaccination) | 
| Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.56 on 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%. | Day 64 (seven weeks after second AV7909 vaccination) | 
| Percentage of AV7909 Participants and BioThrax Participants With TNA NF50 ≥0.29 at Day 64 | 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%. | Day 64 (seven weeks after second AV7909 vaccination; five weeks after third BioThrax vaccination) | 
| Incidence of Serious Adverse Events | 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. | Day 1 though Day 394 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.15 on Day 29. | 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. | Day 29 (two weeks after second AV7909 vaccination) | 
| Incidence of Adverse Events | 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. | Day 1 through Day 64 | 
| Incidence of Adverse Events of Special Interest (Events of Autoimmune Etiology) | 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. | Day 1 through Day 394 | 
| Incidence of Solicited Systemic Reactogenicity Events | Incidence of any solicited systemic reactogenicity reaction after any AV7909 or BioThrax vaccination. | Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day) | 
| Incidences of Solicited Injection Site Reactogenicity Events | Incidence of any solicited injection site reactogenicity reaction after any AV7909 (Lots 1, 2 or 3) or BioThrax vaccination. | Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anthrax, AV7909, BioThrax, Bacillus anthracis, Anthrax Vaccine Adsorbed, Post-exposure Prophylaxis, Vaccine, CPG 7909, Adjuvant