Clinical trial NCT03877926: VELOCITY: An Anthrax Vaccine Clinical Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anthrax
Keywords: Anthrax
AV7909
BioThrax
Bacillus anthracis
Anthrax Vaccine Adsorbed
Post-exposure Prophylaxis
Vaccine
CPG 7909
Adjuvant
Lead sponsor: Emergent BioSolutions
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2019-03-18
Enrollment: 3862
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.
17. Member or family member of the investigator site team.
18. 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.

Primary outcomes:
measure: Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) 50% Neutralization Factor (NF50) at Day 64
timeFrame: Day 64 (seven weeks after second AV7909 vaccination)
measure: Percentage of Participants in AV7909 Lot 1, Lot 2 and Lot 3 Groups Achieving a TNA NF50 ≥0.56 on Day 64
timeFrame: Day 64 (seven weeks after second AV7909 vaccination)
measure: Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.56 on Day 64
timeFrame: Day 64 (seven weeks after second AV7909 vaccination)
measure: Percentage of AV7909 Participants and BioThrax Participants With TNA NF50 ≥0.29 at Day 64
timeFrame: Day 64 (seven weeks after second AV7909 vaccination; five weeks after third BioThrax vaccination)
measure: Incidence of Serious Adverse Events
timeFrame: Day 1 though Day 394
Secondary outcomes:
measure: Percentage of AV7909 Participants Achieving a TNA NF50 ≥0.15 on Day 29.
timeFrame: Day 29 (two weeks after second AV7909 vaccination)
measure: Incidence of Adverse Events
timeFrame: Day 1 through Day 64
measure: Incidence of Adverse Events of Special Interest (Events of Autoimmune Etiology)
timeFrame: Day 1 through Day 394
measure: Incidence of Solicited Systemic Reactogenicity Events
timeFrame: Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day)
measure: Incidences of Solicited Injection Site Reactogenicity Events
timeFrame: Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Achieve Clinical Research, LLC
state: Alabama
city: Huntsville
country: United States
facility: Optimal Research, LLC
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research, an AMR company
state: Alabama
city: Phoenix
country: United States
facility: Central Phoenix Medical Clinic, LLC
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Consortium, an AMR company
state: Arizona
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: San Diego
country: United States
facility: Optimal Research, LLC
state: California
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Melbourne
country: United States
facility: Optimal Research, LLC
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center, Inc
state: Florida
city: Savannah
country: United States
facility: Meridian Clinical Research, LLC
state: Georgia
city: Boise
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Champaign
country: United States
facility: Christie Clinic, LLC
state: Illinois
city: Peoria
country: United States
facility: Optimal Research, LLC
state: Illinois
city: West Des Moines
country: United States
facility: The Iowa Clinic, PC
state: Iowa
city: Augusta
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Hutchinson
country: United States
facility: Hutchinson Clinic
state: Kansas
city: Lenexa
country: United States
facility: Johnson County Clin-Trials, LLC
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Metairie
country: United States
facility: Benchmark Research New Orleans
state: Louisiana
city: Rockville
country: United States
facility: Optimal Research, LLC
state: Maryland
city: Kansas City
country: United States
facility: The Center for Pharmaceutical Research, an AMR company
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada LLC
state: Nevada
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc.
state: Ohio
city: Grove City
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: Norman
country: United States
facility: Lynn Institute of Norman
state: Oklahoma
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center, Inc
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Nashville
country: United States
facility: Clinical Research Associates, Inc.
state: Tennessee
city: Austin
country: United States
facility: Tekton Research
state: Texas
city: Fort Worth
country: United States
facility: Benchmark Research
state: Texas
city: San Angelo
country: United States
facility: Benchmark Research San Angelo
state: Texas
city: Tomball
country: United States
facility: Martin Diagnostic Clinic
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
Study officials:
affiliation: Emergent BioSolutions
name: Gideon Akintunde, MD
role: STUDY_DIRECTOR
References: