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VELOCITY: An Anthrax Vaccine Clinical Study

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ClinicalTrials.gov Identifier: NCT03877926
Recruitment Status : Active, not recruiting
First Posted : March 18, 2019
Last Update Posted : July 10, 2019
Sponsor:
Collaborator:
Biomedical Advanced Research and Development Authority
Information provided by (Responsible Party):
Emergent Product Development Gaithersburg, Inc.

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).

Condition or disease Intervention/treatment Phase
Anthrax Biological: AV7909 Biological: BioThrax Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3861 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Actual Study Start Date : March 11, 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anthrax

Arm Intervention/treatment
Experimental: AV7909 Lot 1
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
AV7909 consists of Anthrax Vaccine Adsorbed (AVA) drug substance and CPG 7909 adjuvant. AVA drug substance is identical in composition and manufacturing process to commercial BioThrax. BioThrax is currently licensed for post-exposure prophylaxis and pre-exposure prophylaxis of anthrax disease in persons at high risk of exposure. CPG 7909 is an immunostimulatory synthetic oligodeoxynucleotide that functions as an adjuvant. It is designed to induce an enhanced immune response.

Experimental: AV7909 Lot 2
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
AV7909 consists of Anthrax Vaccine Adsorbed (AVA) drug substance and CPG 7909 adjuvant. AVA drug substance is identical in composition and manufacturing process to commercial BioThrax. BioThrax is currently licensed for post-exposure prophylaxis and pre-exposure prophylaxis of anthrax disease in persons at high risk of exposure. CPG 7909 is an immunostimulatory synthetic oligodeoxynucleotide that functions as an adjuvant. It is designed to induce an enhanced immune response.

Experimental: AV7909 Lot 3
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
AV7909 consists of Anthrax Vaccine Adsorbed (AVA) drug substance and CPG 7909 adjuvant. AVA drug substance is identical in composition and manufacturing process to commercial BioThrax. BioThrax is currently licensed for post-exposure prophylaxis and pre-exposure prophylaxis of anthrax disease in persons at high risk of exposure. CPG 7909 is an immunostimulatory synthetic oligodeoxynucleotide that functions as an adjuvant. It is designed to induce an enhanced immune response.

Active Comparator: BioThrax
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 will be administered, per the study visit schedule.
Biological: BioThrax
BioThrax (Anthrax Vaccine Adsorbed; AVA), is currently licensed for post-exposure prophylaxis and pre-exposure prophylaxis of anthrax disease in persons at high risk of exposure.




Primary Outcome Measures :
  1. The Confidence Interval (CI) for the ratios of geometric mean of Toxin Neutralizing Antibody (TNA) 50% neutralization factor (NF50) [ Time Frame: Day 1 through Day 64 ]
    Equivalent immunogenicity across three consecutive AV7909 lots as demonstrated by the 95% Confidence interval (CI) for the ratios of geometric mean TNA NF50 at Day 64 for each of the three lot-to-lot comparisons to be within 0.5 and 2.0.

  2. Protective level of immunogenicity [ Time Frame: Day 1 through Day 64 ]
    Protective level of immunogenicity in all three consecutive AV7909 lots as demonstrated by the lower bound of the two-sided 95% CI to be ≥40% for the proportions of AV7909 subjects in each of the three lots achieving a TNA NF50 ≥0.56 at Day 64. A 70% probability of survival was associated with a TNA NF50 level of 0.56 in rabbits exposed to Bacillus anthracis, the bacteria that causes anthrax.

  3. Proportion of AV7909 participants achieving a TNA NF50 ≥0.56 on Day 64. [ Time Frame: Day 1 through Day 64 ]
    Lower bound of the two-sided 95% CI is ≥40% for the proportion of AV7909 participants in Groups 1-3 (three lots pooled) achieving a TNA NF50 ≥0.56 on Day 64.

  4. Non-inferiority of AV7909 to BioThrax [ Time Frame: Day 1 through Day 64 ]
    Non-inferiority of AV7909 to BioThrax at Day 64 as determined by the two-sided lower 95% CI of the difference in the proportion of AV7909 participants (three lots pooled) with a TNA NF50 ≥0.29 and the proportion of BioThrax participants with a TNA NF50 ≥0.29 being greater than -15%. A 70% probability of survival was associated with a TNA NF50 level of 0.29 in nonhuman primates administered BioThrax.

  5. Incidences of Serious Adverse Events [ Time Frame: Day 1 though Day 394 ]
    Incidences of Serious Adverse Events from the time of the first vaccination on Day 1 through the 12-month safety follow-up telephone call following the last vaccination.


Secondary Outcome Measures :
  1. Proportion of AV7909 participants achieving a TNA NF50 ≥0.15 on Day 29. [ Time Frame: Day 1 through Day 29 ]
    Lower bound of the two-sided 95% CI will be ≥67% for the proportion of AV7909 participants in Groups 1-3 (three lots pooled) achieving a TNA NF50 ≥0.15 on Day 29. A 70% probability of survival was associated with a TNA NF50 level of 0.15 in nonhuman primates administered AV7909.

  2. Incidences of Adverse Events [ Time Frame: Day 1 through Day 64 ]
    Incidences of Adverse Events from the time of the first vaccination on Day 1 through Day 64

  3. Incidences of clinical laboratory abnormalities [ Time Frame: Day 1 through Day 64 ]
    Incidences of clinical laboratory abnormalities

  4. Incidences of autoimmune-associated Adverse Events of Special Interest [ Time Frame: Day 1 through Day 394 ]
    Incidences of autoimmune-associated Adverse Events of Special Interest from the time of the first vaccination on Day 1 through the 12-month safety follow-up telephone call following the last vaccination

  5. Incidences of solicited systemic reactions [ Time Frame: Day 1-7, Day 15-21, Day 29-35 (within 7 days after each vaccination, inclusive of the vaccination day) ]
    Incidences of solicited systemic reactions by severity following each vaccination as reported in participant e-diaries

  6. Incidences of solicited injection site reactions [ Time Frame: 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 reactions by severity following each vaccination as reported in participant e-diaries



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03877926


  Show 35 Study Locations
Sponsors and Collaborators
Emergent Product Development Gaithersburg, Inc.
Biomedical Advanced Research and Development Authority

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Responsible Party: Emergent Product Development Gaithersburg, Inc.
ClinicalTrials.gov Identifier: NCT03877926     History of Changes
Other Study ID Numbers: EBS.AVA.212
First Posted: March 18, 2019    Key Record Dates
Last Update Posted: July 10, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Emergent Product Development Gaithersburg, Inc.:
Anthrax
AV7909
BioThrax
Bacillus anthracis
Anthrax Vaccine Adsorbed
Post-exposure Prophylaxis
Vaccine
CPG 7909
Adjuvant
Additional relevant MeSH terms:
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Anthrax
Bacillaceae Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs