AnthraxPhase 2B-SAFENCT03518125
BARDA Securing Anthrax Immunity For the Elderly
A Phase 2 study testing BioThrax and AV7909 in people with Anthrax, run by Biomedical Advanced Research and Development Authority at 4 sites in United States.
Trial summary
This study is designed to assess the safety and ability of BioThrax and AV7909 anthrax vaccines to generate an immune response in adults ≥ 66 years of age in stable health in comparison to adults 18-50 years of age in stable health. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Anthrax
- What is being tested?
- BioThrax and AV7909
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 305 participants
- Where
- 4 sitesUnited States
- Study dates
- 9 May 2018to 9 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or nonpregnant females, 66 years of age or older at the time of randomization for the elderly population, or 18 through 50 years of age at the time of randomization for the younger population.
- Females who are of childbearing potential and are sexually active with a male partner must agree to use an acceptable method of birth control from Screening to Day 64 and must have used a reliable birth control method for at least 2 months prior to Screening.
- A female of childbearing potential is defined as post onset menarche and pre-menopausal female capable of becoming pregnant. This does not include females who meet any of the following conditions: menopausal >2 years, tubal ligation >1 year, bilateral salpingo-oophorectomy, or hysterectomy.
- Adequate contraception is defined as a contraceptive method with a failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label. Examples include: oral contraceptives, either combined or progestogen alone; injectable progestogen; implants of etenogestrel or levonorgestrel; estrogenic vaginal ring; percutaneous contraceptive patches; intrauterine device or intrauterine system; male partner sterilization at least 6 months prior to the female subject's Screening Visit, and this male is the sole partner for that subject (the information on the male partner's sterility can come from the site personnel's review of the subject's medical records or interview with the subject on her medical history); male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository); male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).
- Able to provide written informed consent prior to initiation of any study procedures. As part of the consent process, subjects must be able to demonstrate understanding by passing the "Assessment of Understanding Questionnaire" within 2 attempts. Passing is defined as being able to answer all questions correctly.
- In relatively stable health based on site investigator's judgment, as determined by medical history, physical examination, and the following criteria:
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- Stable health for age (defined as no new conditions per medical history, new medications in a different therapeutic class, or change in daily dose of existing prescription medications within the 45 days preceding Screening). Effective treatment (to resolution) of an acute infection (e.g., urinary tract infection, cellulitis, otitis, or bronchitis) with an antibiotic within 45 days preceding Screening will not be considered a deviation from this inclusion criterion as long as the antibiotic therapy was completed at least one week prior to Screening and no signs or symptoms of the infection have been present since the completion of treatment. Any prescription change that is due to change of health care provider or insurance company, or that is made for reasons that do not reflect a change in disease status (e.g., financial considerations), as long as within the same general class of medication, will not be considered a deviation from this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site investigator, will not be considered a deviation from this inclusion criterion.
- Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site investigator, these pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and their use is not for management of a worsening of medical diagnosis or condition. Note: Topical, nasal, and inhaled medications (with the exception of steroids, as outlined in the subject exclusion criteria) and vitamins are permitted.
- Have a body mass index (BMI) less than 35.0 kg/m2 at Screening. (BMI will not be reassessed prior to subsequent vaccinations.)
- Have access to a consistent and reliable means of telephone contact, which may be home, workplace, or by personal mobile electronic device.
- Are available and able to comply with all study visits.
Who cannot join
- Females who have a positive urine pregnancy test at Screening or within 24 hours prior to each study vaccination or women who are breastfeeding.
- Have a requirement for skilled nursing care.
- Have a history of severe reactions to components of AVA or CPG 7909, e.g., formaldehyde, benzethonium chloride (phemerol), or aluminum.
- Have a history of latex sensitivity.
- Have a history of ever receiving a vaccine for anthrax prior to Screening, or had an anthrax infection.
- Have any medical, psychiatric, or social condition that, in the opinion of the site investigator, unfavorably alters the risk-benefit of subject participation, or is likely to interfere with study compliance or assessments, or is likely to confound interpretation of safety or immunogenicity data.
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- Have any diagnosis, current or past, of a potentially immune-mediated medical condition, such as Guillain-Barré syndrome, narcolepsy, or an autoimmune or chronic inflammatory disease.
- Have any diagnosis, current or past, of schizophrenia or bipolar disorder.
- Have been hospitalized for psychiatric illness, have a history of suicide attempt, or confinement for danger to self or others within the preceding 10 years prior to Screening and each study vaccination.
- Have a history of alcohol or drug abuse (per investigator's judgment) within 5 years prior to Screening and each study vaccination, or test positive for drugs of abuse at Screening (including for cannabis, even where legal). Benzodiazepines for anxiety disorders and stimulants for attention deficit hyperactivity disorder are not exclusionary if the subject has been on a stable dose for more than 3 months prior to Screening and each study vaccination and if the subject can produce a valid, current prescription for the medication. Propoxyphene, opioids, or combinations containing these medications (including as used for opioid addiction) are not permitted regardless of prescription status. Note: A positive Screening urine drug screen may not be repeated. (Drug screen will not be repeated prior to subsequent vaccinations.)
- Have known human immunodeficiency virus (HIV), or acute or chronic hepatitis B or hepatitis C infection based on medical history; or test positive for any of these at Screening. Subjects who have been effectively treated for hepatitis C, as evidenced by a negative hepatitis C ribonucleic acid (RNA) confirmation test and who no longer require antiviral therapy, are eligible for participation. (Screening tests will not be repeated prior to subsequent vaccinations.)
- Have known active neoplastic disease or a history of any hematologic malignancy. However, subjects with superficial skin cancer who do not require intervention other than local excision are not excluded.
- Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy (cytotoxic) or radiation therapy within 3 years prior to Screening and each study vaccination.
- Have taken any systemic immunosuppressive agents, including immunomodulators, 6 months prior to Screening and each study vaccination. Allergen immunotherapy (desensitization) is not exclusionary. Allergen immunotherapy (desensitization) does not include systemic antibodies such as benralizumab, mepolizumab, or omalizumab; these are exclusionary.
- Are suffering from or have a history of neuralgia, paresthesia, or neuritis within 90 days prior to Screening and each study vaccination; or have any history of stroke.
- Have had convulsions or encephalomyelitis within three years prior to Screening and each study vaccination.
- Have received immunoglobulin or other blood products (with the exception of Rho[D] immune globulin) within 90 days prior to Screening and each study vaccination.
- Have received an experimental agent within 180 days prior to the first study vaccination, or expects to participate in another clinical trial with an interventional agent during the study period. This includes licensed or unlicensed vaccines, drugs, biologics, devices, blood products, or medications. Participation in an observational study is not exclusionary as long as it doesn't interfere with study visits or procedures (e.g., blood collection volume restrictions).
- Have taken oral or parenteral corticosteroids of any dose within 30 days prior to each study vaccination.
- Have taken high-dose inhaled corticosteroids within 30 days prior to each study vaccination. High-dose is defined as >800 mcg/day of beclomethasone dipropionate or equivalent. Lower doses of inhaled corticosteroids are not exclusionary.
- Have received any licensed live vaccine within 30 days prior to the first study vaccination or planned receipt from the first study vaccination through Visit 10 (Day 64).
- Have received any licensed inactivated vaccine within 14 days prior to the first study vaccination or planned receipt from the first study vaccination through Visit 10 (Day 64).
- Have an acute illness, as determined by the site investigator, within 72 hours prior to each study vaccination.
- If subject's oral temperature is above 100.0°F (37.8°C), the subject may be re-assessed for eligibility within the visit window (+3 Days).
- An acute illness that is nearly resolved, with only minor residual symptoms remaining, is allowable if, in the opinion of the site investigator, the residual symptoms will not interfere with the ability of study staff to assess safety parameters as required by the protocol.
- For bacterial infections that have been successfully treated with antibiotics, inclusion criterion 4a applies.
- Have a history of myocardial infarction or ischemia, or have electrocardiogram (ECG) findings of myocardial infarction, ischemia, strain, complete bundle branch block, or ventricular arrhythmias (other than unifocal premature ventricular contractions ≤2/minute). Additionally, other cardiac history or ECG findings, which in the opinion of the investigator represent a potentially unstable or unacceptably high risk of an adverse cardiac outcome, are exclusionary. (ECG will not be repeated prior to subsequent vaccinations.)
- Have any laboratory test result or clinical findings (including vital signs) that singly or in combination are, in the investigator's opinion, likely to unfavorably alter the risk-benefit of subject participation or to confound study safety or immunogenicity results. Additionally, the following are exclusionary:
- Any clinically significant Grade 3 laboratory or vital sign result, or any Grade 4 laboratory or vital sign result (regardless of assessed significance) at Screening. For subsequent vaccinations, abnormal laboratory results and vital sign results postvaccination will be assessed against the rules for early termination of dosing.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times the upper limit of normal (ULN), or bilirubin >1.5 times the ULN unless isolated Gilbert's syndrome.
- Creatinine >1.5 times ULN for age and sex.
- White blood cell count <3,000/μL or >12,500/μL; absolute neutrophil count <1200/μL; absolute lymphocyte count <750/μL; hemoglobin <10 g/dL females, or <11.5 g/dL males; platelet count <75,000/μL.
- Hemoglobin A1C (HbA1C) >7.0% at Screening. (HbA1C will not be repeated prior to subsequent vaccinations.)
- Subjects cannot be rescreened for exclusionary laboratory test results. Potentially exclusionary vital sign results may be repeated, but unless they have resolved to a Grade 3 designation or less and are not considered clinically significant, the subject should be excluded. The most recent laboratory and vital sign results will be used when determining eligibility for subsequent vaccinations.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Johnson County Clin-Trials
Lenexa, Kansas, 66219
Coastal Carolina Research Center
Mt. Pleasant, South Carolina, 29464
Clinical Research Associates, Inc.
Nashville, Tennessee, 29464
JBR Clinical Research
Salt Lake City, Utah, 84124
About this study
Official title: Randomized, Active-Comparison, Double-Blind, Phase 2 Study to Assess the Safety and Immunogenicity of Anthrax Vaccine Adsorbed (BioThrax®) Without and With CPG 7909 Adjuvant (AV7909 Anthrax Vaccine), Using a Post-Exposure Prophylaxis Dosing Regimen in Adults 66 Years of Age or Older in Stable Health in Comparison to Adults 18-50 Years of Age in Stable Health
This study is designed to assess the safety and ability of BioThrax and AV7909 anthrax vaccines to generate an immune response in adults ≥ 66 years of age in stable health in comparison to adults 18-50 years of age in stable health.
Read the detailed description
This is a phase 2, randomized, active-controlled, double-blinded, multi-site study to assess the safety and immunogenicity of BioThrax (Anthrax Vaccine Adsorbed) and AV7909 (Anthrax Vaccine Adsorbed plus CPG 7909 adjuvant) using a post-exposure prophylaxis dosing regimen in adults ≥ 66 years of age in stable health. The safety and immunogenicity profile of BioThrax and AV7909 in adults ≥ 66 years of age will also be compared to the safety and immunogenicity profile of subjects 18-50 years of age in stable health. The main study goal is to determine optimal dosing for AV7909 in the elderly population. Subjects will receive either 3 doses of BioThrax, 3 doses of AV7909, or 2 doses of AV7909 and 1 dose of placebo. Doses will be administered approximately 14 days apart. Subjects will be followed for safety assessment for 12 months following the last dose. The expected study duration is approximately 14 months per subject.
- Conditions
- Anthrax
- Being tested
- BioThrax, AV7909, Sodium chloride injection USP, 0.9% (placebo)
- Keywords
- Anthrax, Bacillaceae Infections, Gram-Positive Bacterial Infections, Bacterial Infections, Anthrax Vaccine Adsorbed, BioThrax, AV7909, CPG 7909, Adjuvant, Vaccines, Post-exposure Prophylaxis
- Medical subject headings
- Anthrax, Bacillaceae Infections, Gram-Positive Bacterial Infections, Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BioThraxBiological
Other Names:
Anthrax Vaccine Adsorbed (AVA)
AV7909Biological
Also called AV7909 Anthrax Vaccine Adsorbed, NuThrax
Anthrax Vaccine Absorbed plus CPG 7909 Adjuvant
Sodium chloride injection USP, 0.9% (placebo)Drug
Other Names:
Saline Solution
| Study group | Role | What they receive |
|---|---|---|
| Age ≥ 66, BioThrax (Days 1, 15, 29) | Experimental | Subjects dosed on Days 1, 15, and 29 with 0.5 mL BioThrax. Receives: Biological: BioThrax |
| Age ≥ 66, AV7909 (Days 1, 15, 29) | Experimental | Subjects dosed on Days 1, 15, and 29 with 0.5 mL AV7909. Receives: Biological: AV7909 |
| Age ≥ 66, AV7909 (Days 1 and 15) | Experimental | Subjects dosed on Days 1 and 15 with 0.5 mL AV7909 and on Day 29 with 0.5 mL placebo. Receives: Biological: AV7909; Drug: Sodium chloride injection USP, 0.9% (placebo) |
| Age ≥ 66, AV7909 (Days 1 and 29) | Experimental | Subjects dosed on Days 1 and 29 with 0.5 mL AV7909 and on Day 15 with 0.5 mL placebo. Receives: Biological: AV7909; Drug: Sodium chloride injection USP, 0.9% (placebo) |
| Age18-50, BioThrax (Days 1, 15, 29) | Active comparator | Subjects dosed on Days 1, 15, and 29 with 0.5 mL BioThrax. Receives: Biological: BioThrax |
| Age 18-50, AV7909 (Days 1 and 15) | Active comparator | Subjects dosed on Days 1 and 15 with 0.5 mL AV7909 and on Day 29 with 0.5 mL placebo. Receives: Biological: AV7909; Drug: Sodium chloride injection USP, 0.9% (placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Solicited Local Reactogenicity Symptoms
Count of participants who experienced at least one of the following during the time frame specified on the arm which received the vaccination: injection site warmth, tenderness, itching, pain, restriction of range of arm motion, erythema/redness, palpable or observable lump, induration/swelling, or bruising.
Measured: Day 1-8, Day 15-22, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)
Solicited Systemic Reactogenicity Symptoms
Count of participants who experienced at least one of the following during the time frame specified on the arm which received the vaccination: fatigue, myalgia/muscle ache, headache, and fever.
Measured: Day 1-8, Day 15-22, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)
Seroprotection Based on Toxin Neutralization Antibody (TNA) 50% Neutralization Factor (NF50) Antibody Level, Defined as a TNA NF50 Antibody Level ≥0.56
The percentage of participants achieving seroprotection based on TNA NF50. 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.
Measured: Day 64
Secondary outcomes (12)
Treatment-emergent Unsolicited Adverse Events (AEs)
The count of participants who experienced at least one post-vaccination unsolicited AE (i.e. AEs not included in the solicited local and systemic adverse event list through Day 50 and those reported as a serious AE, medically attended adverse event (MAAE), or potentially immune-mediated medical condition (PIMMC) after Day 50).
Measured: Day 1 through Day 394
Treatment-emergent Serious Adverse Events (SAEs)
The count of participants who experienced at least one post-vaccination SAE
Measured: Day 1 through Day 394
Treatment-emergent Medically Attended Adverse Events (MAAEs)
Count of participants who experienced at least one adverse event that requires a visit to medical personnel, including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason occurring post-vaccination.
Measured: Day 1 through Day 394
Treatment-emergent Potentially Immune Mediated Medical Conditions (PIMMCs)
Count of participants who experienced at least one medical condition that was potentially immune mediated occurring post-vaccination
Measured: Day 1 through Day 394
Solicited Local Reactogenicity Symptoms on the Contralateral Arm
Count of participants who experienced at least one of the following during the time frame specified on the arm which did not receive the vaccination: injection site warmth, tenderness, itching, pain, restriction of range of arm motion, erythema/redness, palpable or observable lump, induration/swelling, or bruising.
Measured: Day 1-8, Day 15-22, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)
TNA NF50 Antibody Levels
A higher TNA NF50 antibody level means a better immune response to the vaccine.
Measured: Days 1, 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
TNA Effective Dilution Resulting in 50% Neutralization (ED50) Antibody Levels
A higher TNA ED50 antibody level means a better immune response to the vaccine.
Measured: Days 1, 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
Enzyme-linked Immunosorbent Assay (ELISA) Anti-protective Antigen (Anti-PA) Immunoglobulin G (IgG) Antibody Levels
A higher ELISA anti-PA IgG antibody level means a better immune response to the vaccine.
Measured: Days 1, 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
Seroprotection Based on TNA NF50, Defined as a TNA NF50 Antibody Level ≥0.56
The percentage of participants achieving seroprotection based on TNA NF50 antibody level. 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.
Measured: Days 1, 8, 22, 29, 36, 43, 50, 85, 181, and 394
Seroconversion Based on TNA NF50, Defined as a ≥4-fold Increase Over Pre-vaccination Levels, or a ≥4-fold Increase Over the Lower Limit of Quantification (LLOQ) if the Pre-vaccination Value is Below the LLOQ
The percentage of subjects obtaining seroconversion based on TNA NF50 antibody levels. Seroconversion represents the minimum intended effect of vaccination.
Measured: Days 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
Seroconversion Based on TNA ED50, Defined as a ≥4-fold Increase Over Pre-vaccination Levels, or a ≥4-fold Increase Over the Lower Limit of Quantification (LLOQ) if the Pre-vaccination Value is Below the LLOQ
The percentage of subjects obtaining seroconversion based on TNA ED50 antibody levels. Seroconversion represents the minimum intended effect of vaccination.
Measured: Days 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
Seroconversion Based on ELISA Anti-PA IgG, Defined as a ≥4-fold Increase Over Pre-vaccination Levels, or a ≥4-fold Increase Over the Lower Limit of Quantification (LLOQ) if the Pre-vaccination Value is Below the LLOQ
The percentage of subjects obtaining seroconversion based on ELISA anti-PA IgG antibody levels. Seroconversion represents the minimum intended effect of vaccination.
Measured: Days 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2018
- Study start9 May 2018
- Primary completion14 Jan 2019
- Study completion9 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AnthraxStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized to receive either BioThrax or AV7909. Randomization will be stratified by sex and age (18-50, 66-74, and ≥75 years). Subjects ≥66 years of age will be randomized 1:1:1:1 within stratum across 4 treatment arms (approximately 50 subjects per group), and subjects 18 through 50 years of age will be randomized 1:1 within stratum across 2 treatment arms (approximately 50 subjects per group). Once randomized, subjects will receive 3 vaccinations, each separated by approximately 14 days, on Day 1, Day 15, and Day 29, based on their assigned treatment arm.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 305 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biomedical Advanced Research and Development Authority
- Sponsor type
- US federal agency
- Collaborators
- Rho, Inc.
- Responsible party
- Sponsor
- Investigators
- Carlos Fierro, MD, Principal investigator, Johnson County Clin-TrialsDerek Muse, MD, Principal investigator, JBR Clinical ResearchStephan Sharp, MD, Principal investigator, Clinical Research Associates, Inc.Cynthia Strout, MD, Principal investigator, Coastal Carolina Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03518125
- Sponsor's protocol ID
- BP-C-17001
- Other IDs
- HHSO100201400004I
- Acronym
- B-SAFE
- Status last verified
- Jul 2020
- First submitted
- 24 Apr 2018
- Last updated
- 21 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wolfe DN, Espeland EM, Gao Y, Lu D, Blatner G, Amass K, Horwith G, Tong XM, Hopkins R, David GL, Jepson BM, King JC Jr. Evaluation of BioThrax(R) and AV7909 anthrax vaccines in adults 66 years of age or older. Vaccine. 2020 Nov 25;38(50):7970-7976. doi: 10.1016/j.vaccine.2020.10.053. Epub 2020 Oct 28.
PubMed 33129609
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Active-Comparison, Double-Blind, Phase 2 Study to Assess the Safety and Immunogenicity of Anthrax Vaccine Adsorbed (BioThrax®) Without and With CPG 7909 Adjuvant (AV7909 Anthrax Vaccine), Using a Post-Exposure Prophylaxis Dosing Regimen in Adults 66 Years of Age or Older in Stable Health in Comparison to Adults 18-50 Years of Age in Stable Health
- ClinicalTrials.gov ID
- NCT03518125
- Acronym / sponsor ID
- B-SAFE / BP-C-17001
- Conditions
- Anthrax
- Keywords
- Anthrax, Bacillaceae Infections, Gram-Positive Bacterial Infections, Bacterial Infections, Anthrax Vaccine Adsorbed, BioThrax, AV7909, CPG 7909
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 305 participants (actual)
- Lead sponsor
- Biomedical Advanced Research and Development AuthorityUS federal agency
- Collaborators
- Rho, Inc.
- Study start
- 9 May 2018 (actual)
- Primary completion
- 14 Jan 2019 (actual)
- Study completion
- 9 Dec 2019 (actual)
- First posted
- 8 May 2018 (actual)
- Results
- Posted 9 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to assess the safety and ability of BioThrax and AV7909 anthrax vaccines to generate an immune response in adults ≥ 66 years of age in stable health in comparison to adults 18-50 years of age in stable health.
Detailed description
This is a phase 2, randomized, active-controlled, double-blinded, multi-site study to assess the safety and immunogenicity of BioThrax (Anthrax Vaccine Adsorbed) and AV7909 (Anthrax Vaccine Adsorbed plus CPG 7909 adjuvant) using a post-exposure prophylaxis dosing regimen in adults ≥ 66 years of age in stable health. The safety and immunogenicity profile of BioThrax and AV7909 in adults ≥ 66 years of age will also be compared to the safety and immunogenicity profile of subjects 18-50 years of age in stable health. The main study goal is to determine optimal dosing for AV7909 in the elderly population. Subjects will receive either 3 doses of BioThrax, 3 doses of AV7909, or 2 doses of AV7909 and 1 dose of placebo. Doses will be administered approximately 14 days apart. Subjects will be followed for safety assessment for 12 months following the last dose. The expected study duration is approximately 14 months per subject.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
- Model description
- Subjects will be randomized to receive either BioThrax or AV7909. Randomization will be stratified by sex and age (18-50, 66-74, and ≥75 years). Subjects ≥66 years of age will be randomized 1:1:1:1 within stratum across 4 treatment arms (approximately 50 subjects per group), and subjects 18 through 50 years of age will be randomized 1:1 within stratum across 2 treatment arms (approximately 50 subjects per group). Once randomized, subjects will receive 3 vaccinations, each separated by approximately 14 days, on Day 1, Day 15, and Day 29, based on their assigned treatment arm.
| Arm | Type | Receives |
|---|---|---|
| Age ≥ 66, BioThrax (Days 1, 15, 29) | Experimental | Biological: BioThraxSubjects dosed on Days 1, 15, and 29 with 0.5 mL BioThrax. |
| Age ≥ 66, AV7909 (Days 1, 15, 29) | Experimental | Biological: AV7909Subjects dosed on Days 1, 15, and 29 with 0.5 mL AV7909. |
| Age ≥ 66, AV7909 (Days 1 and 15) | Experimental | Biological: AV7909, Drug: Sodium chloride injection USP, 0.9% (placebo)Subjects dosed on Days 1 and 15 with 0.5 mL AV7909 and on Day 29 with 0.5 mL placebo. |
| Age ≥ 66, AV7909 (Days 1 and 29) | Experimental | Biological: AV7909, Drug: Sodium chloride injection USP, 0.9% (placebo)Subjects dosed on Days 1 and 29 with 0.5 mL AV7909 and on Day 15 with 0.5 mL placebo. |
| Age18-50, BioThrax (Days 1, 15, 29) | Active comparator | Biological: BioThraxSubjects dosed on Days 1, 15, and 29 with 0.5 mL BioThrax. |
| Age 18-50, AV7909 (Days 1 and 15) | Active comparator | Biological: AV7909, Drug: Sodium chloride injection USP, 0.9% (placebo)Subjects dosed on Days 1 and 15 with 0.5 mL AV7909 and on Day 29 with 0.5 mL placebo. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or nonpregnant females, 66 years of age or older at the time of randomization for the elderly population, or 18 through 50 years of age at the time of randomization for the younger population.
- Females who are of childbearing potential and are sexually active with a male partner must agree to use an acceptable method of birth control from Screening to Day 64 and must have used a reliable birth control method for at least 2 months prior to Screening.
- Able to provide written informed consent prior to initiation of any study procedures. As part of the consent process, subjects must be able to demonstrate understanding by passing the "Assessment of Understanding Questionnaire" within 2 attempts. Passing is defined as being able to answer all questions correctly.
- In relatively stable health based on site investigator's judgment, as determined by medical history, physical examination, and the following criteria:
- Have a body mass index (BMI) less than 35.0 kg/m2 at Screening. (BMI will not be reassessed prior to subsequent vaccinations.)
Key exclusion criteria (34 listed)
- Females who have a positive urine pregnancy test at Screening or within 24 hours prior to each study vaccination or women who are breastfeeding.
- Have a requirement for skilled nursing care.
- Have a history of severe reactions to components of AVA or CPG 7909, e.g., formaldehyde, benzethonium chloride (phemerol), or aluminum.
- Have a history of latex sensitivity.
- Have a history of ever receiving a vaccine for anthrax prior to Screening, or had an anthrax infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BioThraxOther Names: Anthrax Vaccine Adsorbed (AVA) | Biological | Age ≥ 66, BioThrax (Days 1, 15, 29), Age18-50, BioThrax (Days 1, 15, 29) |
| AV7909Also: AV7909 Anthrax Vaccine Adsorbed, NuThraxAnthrax Vaccine Absorbed plus CPG 7909 Adjuvant | Biological | Age 18-50, AV7909 (Days 1 and 15), Age ≥ 66, AV7909 (Days 1 and 15), Age ≥ 66, AV7909 (Days 1 and 29), Age ≥ 66, AV7909 (Days 1, 15, 29) |
| Sodium chloride injection USP, 0.9% (placebo)Other Names: Saline Solution | Drug | Age 18-50, AV7909 (Days 1 and 15), Age ≥ 66, AV7909 (Days 1 and 15), Age ≥ 66, AV7909 (Days 1 and 29) |
Primary outcome
Solicited Local Reactogenicity Symptoms
Time frame: Day 1-8, Day 15-22, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)
Count of participants who experienced at least one of the following during the time frame specified on the arm which received the vaccination: injection site warmth, tenderness, itching, pain, restriction of range of arm motion, erythema/redness, palpable or observable lump, induration/swelling, or bruising.
Solicited Systemic Reactogenicity Symptoms
Time frame: Day 1-8, Day 15-22, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)
Count of participants who experienced at least one of the following during the time frame specified on the arm which received the vaccination: fatigue, myalgia/muscle ache, headache, and fever.
Seroprotection Based on Toxin Neutralization Antibody (TNA) 50% Neutralization Factor (NF50) Antibody Level, Defined as a TNA NF50 Antibody Level ≥0.56
Time frame: Day 64
The percentage of participants achieving seroprotection based on TNA NF50. 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.
12 secondary outcomes
Treatment-emergent Unsolicited Adverse Events (AEs)
Time frame: Day 1 through Day 394
Treatment-emergent Serious Adverse Events (SAEs)
Time frame: Day 1 through Day 394
Treatment-emergent Medically Attended Adverse Events (MAAEs)
Time frame: Day 1 through Day 394
Treatment-emergent Potentially Immune Mediated Medical Conditions (PIMMCs)
Time frame: Day 1 through Day 394
Solicited Local Reactogenicity Symptoms on the Contralateral Arm
Time frame: Day 1-8, Day 15-22, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)
TNA NF50 Antibody Levels
Time frame: Days 1, 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
TNA Effective Dilution Resulting in 50% Neutralization (ED50) Antibody Levels
Time frame: Days 1, 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
Enzyme-linked Immunosorbent Assay (ELISA) Anti-protective Antigen (Anti-PA) Immunoglobulin G (IgG) Antibody Levels
Time frame: Days 1, 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
Seroprotection Based on TNA NF50, Defined as a TNA NF50 Antibody Level ≥0.56
Time frame: Days 1, 8, 22, 29, 36, 43, 50, 85, 181, and 394
Seroconversion Based on TNA NF50, Defined as a ≥4-fold Increase Over Pre-vaccination Levels, or a ≥4-fold Increase Over the Lower Limit of Quantification (LLOQ) if the Pre-vaccination Value is Below the LLOQ
Time frame: Days 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
Seroconversion Based on TNA ED50, Defined as a ≥4-fold Increase Over Pre-vaccination Levels, or a ≥4-fold Increase Over the Lower Limit of Quantification (LLOQ) if the Pre-vaccination Value is Below the LLOQ
Time frame: Days 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
Seroconversion Based on ELISA Anti-PA IgG, Defined as a ≥4-fold Increase Over Pre-vaccination Levels, or a ≥4-fold Increase Over the Lower Limit of Quantification (LLOQ) if the Pre-vaccination Value is Below the LLOQ
Time frame: Days 8, 22, 29, 36, 43, 50, 64, 85, 181, and 394
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33129609Wolfe DN, Espeland EM, Gao Y, Lu D, Blatner G, Amass K, Horwith G, Tong XM, Hopkins R, David GL, Jepson BM, King JC Jr. Evaluation of BioThrax(R) and AV7909 anthrax vaccines in adults 66 years of age or older. Vaccine. 2020 Nov 25;38(50):7970-7976. doi: 10.1016/j.vaccine.2020.10.053. Epub 2020 Oct 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlos Fierro, MD principal investigator
Johnson County Clin-Trials
Derek Muse, MD principal investigator
JBR Clinical Research
Stephan Sharp, MD principal investigator
Clinical Research Associates, Inc.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BioThrax and AV7909 in people with Anthrax, run by Biomedical Advanced Research and Development Authority at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Solicited Local Reactogenicity Symptoms (time frame: Day 1-8, Day 15-22, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03518125, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2020.