HealthyPhase 4AVRPNCT00119067
Anthrax Vaccine Clinical Trial to Assess Dose Reduction and Route Change
A Phase 4 study testing Anthrax Vaccine Adsorbed and Saline injection in people with Healthy, run by Centers for Disease Control and Prevention at 5 sites in United States.
Trial summary
Anthrax Clinical Trial Objectives: To assess whether: Anthrax vaccine (AVA or BioThrax, BioPort Corp. Lansing MI) administered by the intramuscular (IM) route elicits antibody responses that are not inferior (i.e., "non-inferior") to that achieved by the currently licensed schedule. Read more about this study
- Who is it for?
- Ages 18 to 61 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Anthrax Vaccine Adsorbed and Saline injection
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,564 participants
- Where
- 5 sitesUnited States
- Study dates
- May 2002to Feb 2010
- Phase
- Phase 4
- 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 to 61 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Read/sign Informed Consent Document; Female or male, 18 to 61 years old (up to 62nd birthday); Females must agree to exercise adequate birth control from the time of the screening procedures to one month after the last vaccination; willingness/ability to return for all follow-up visits and blood collections for the duration of the study; ability to understand/comply with planned study procedures; agree to complete the Participant Diary (Appendix G) and to report concomitant medications and AEs during the study period; thave two intact upper arms with sufficient subcutaneous and intramuscular tissue in the deltoid regions for vaccine administration.Potential participants with a history of the following conditions remain eligible for study enrollment: gestational diabetes; treated, controlled, uncomplicated hypertension; treated hypo- or hyperthyroidism; cured nonmetastatic cancer; disease-free for 5 years (excluding hematologic malignancies); localized skin cancer, resected (including squamous cell and basal cell carcinomas, participants with a history of melanoma must be disease-free for 5 years); exercise-induced bronchospasm; mild asthma: use of inhalers only for control of symptoms is acceptable (Persons who have required hospitalization for asthma within the previous 2 years or those who require chronic or frequent oral/parenteral steroids will not be eligible; use of low to medium doses of inhaled steroids; history of coronary artery disease, asymptomatic (NYHA Function Class I), on a stable medical regimen. Persons meeting these criteria must be at least 2 years post-myocardial infarction, cardiac bypass surgery, and/or percutaneous coronary intervention (e.g., angioplasty, stent placement, etc) in order to qualify. Persons with a history of cardiac disease must be under the care of a physician.
Who cannot join
- Prior history of anthrax or immunization against anthrax; Known allergy to aluminum hydroxide, formaldehyde, benzethonium chloride, or latex; Pregnant/plans to become pregnant for duration of study/does not agree to use adequate birth control from the time of screening procedures to one month after last vaccination; Used cytotoxic therapy in previous 5 years; Cardiovascular disease with significant likelihood of progression over 5 years; Moderate to severe asthma, chronic obstructive pulmonary disease, other significant pulmonary disease; using high doses of inhaled steroids; Clinically recognized hepatic or renal insufficiency; Inflammatory, vasculitic, or rheumatic disease including systemic lupus erythematosis, polymyalgia rheumatica and rheumatoid arthritis, scleroderma; Known HIV, hepatitis B or hepatitis C infection; Other conditions known to produce or be associated with immune suppression; Neuropathy or other evolving neurologic condition; Unstable/moderate to severe mental illness; Ongoing drug abuse/dependence (including alcohol); Seizure disorder; Active malignancy or history of metastatic or hematologic malignancy; current diabetes; Anyone who plans to receive within 60 days of study entry: cytotoxic therapy, experimental products, a live vaccine outside this trial, immunosuppressive therapy, parenteral immunoglobulin or blood products; Anyone who plans to receive an inactivated vaccine outside this trial within 42 days after study entry;: experimental products, a live vaccine outside this trial, immunosuppressive therapy; Anyone who received an inactivated vaccine outside this trial within 14 days prior to study entry, parenteral immunoglobulin or blood products within three months of study. In addition to conditions listed above, temporary exclusion would result from moderate or severe illness and/or oral temperature >100.4˚F within 3 days of injection or chronic condition that, in opinion of investigator, would render injection unsafe or would interfere with evaluations.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Emory
Atlanta, Georgia, 30322
University of Alabama, Birmingham (UAB)
Birmingham, Alabama, 35294-2050
Baylor
Houston, Texas, 77030
Mayo Clinic
Rochester, Minnesota, 55905
Walter Reed Army Institute for Research (WRAIR)
Silver Spring, Maryland, 20910-7500
About this study
Official title: Anthrax Vaccine Adsorbed: Human Reactogenicity and Immunogenicity Trial to Address Change in Route of Administration and Dose Reduction
Anthrax Clinical Trial Objectives:
To assess whether:
Read more
- Anthrax vaccine (AVA or BioThrax, BioPort Corp. Lansing MI) administered by the intramuscular (IM) route elicits antibody responses that are not inferior (i.e., "non-inferior") to that achieved by the currently licensed schedule.
- BioThrax administered by the IM route and containing fewer numbers of doses elicits antibody responses that are not inferior (i.e., "non-inferior") to that achieved by the currently licensed schedule.
- Differences in reactogenicity exist between the IM and subcutaneous (SQ) administration of BioThrax.
Additionally for the final report we will assess whether:
- Occurrence of adverse events following AVA administration is influenced by selected risk factors.
Read the detailed description
This study is a 43-month prospective, randomized, double-blind, placebo-controlled comparison of immunogenicity and reactogenicity elicited by BioThrax given by different routes of administration (SQ versus IM) and dosing regimens (as many as 8 doses versus as few as 4 doses). Sterile saline is used as the placebo where doses are dropped in regimens using AVA, and in the all-placebo study group.
This study is conducted among a total of 1564 healthy adult men and women (18 to 61 years of age) at five sites in the United States. Participants were randomized into one of 6 study groups with 260 participants per group. One group receives BioThrax given as currently licensed (SQ with 6 doses followed by annual boosters); another group is given placebo IM (130 participants) or SQ (130 participants) in the currently licensed dosing regimen. The four other groups receive BioThrax IM in modified dosing regimens; placebo is given when a dose of BioThrax is omitted from the licensed dosing regimen. There are a total of 25 required visits for this study, during which all participants receive an injection of vaccine or placebo (8 injections total), have a blood sample drawn (16 or 17 total), and have an in-clinic examination for adverse events (22 total).
Immunogenicity is assessed by assaying 16 serial blood samples obtained from all participants and a 17th sample from a subset of participants before vaccination and at other specified times. Total anti-protective antigen IgG antibody (anti-PA IgG) is quantified using a standardized and validated enzyme-linked immunosorbent assay (ELISA); the primary study endpoints are 4-fold rise in antibody titer and antibody concentration relative to the pre-vaccination titers or assay reactivity threshold. A subset of serum samples is also assayed in an in vitro toxin neutralization assay (TNA) to measure the functional activity of anti-BioThrax antibodies. The kinetics of the immune response to BioThrax are examined at 3 time points in the study and blood samples from a subset of participants will be further tested in correlates of protection and immunogenetics substudies. All adverse events (AEs), including vaccine reactogenicity, are actively monitored. While all AEs will be ascertained among study participants, several endpoints will be defined based on the likelihood of their occurrence and/or their clinical importance. Of primary interest is the occurrence of local AEs such as warmth, tenderness, itching, pain, arm motion limitation, erythema, induration, nodule, and bruise. Systemic AEs such as fever, fatigue, muscle ache, headache, temperature, and painful axillary adenopathy are also evaluated.
This study is expected to provide the basis for consideration of change in route of BioThrax administration from SQ to IM and reduction in number of vaccine doses required for primary and booster immunization.
There is an interim analysis of data collected through each participant's first 7 months of this study for consideration in changing the route of BioThrax administration from SQ to IM, and elimination of the 2 week vaccine priming dose.
At the end of the study, the Sponsor will present the entire results of the trial to FDA for consideration in elimination of additional doses from the licensed BioThrax schedule. At that time, the Sponsor will also supplement these data with results from parallel non-human primate challenge studies and additional research on immunologic correlates of protection.
- Conditions
- Healthy
- Being tested
- Anthrax Vaccine Adsorbed, Saline injection
- Keywords
- Anthrax, Vaccine, Immunogenicity, Reactogenicity
- Medical subject headings
- Anthrax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anthrax Vaccine AdsorbedBiological
Also called AVA, BioThrax
Saline injectionBiological
| Study group | Role | What they receive |
|---|---|---|
| Anthrax Vaccine Adsorbed 8-SQ | Active comparator | receive 8 injections of AVA injected SQ at the same points as the original licensure: 0m, 2weeks, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. Receives: Biological: Anthrax Vaccine Adsorbed |
| Anthrax Vaccine Adsorbed 8-IM | Experimental | receive 8 injections of AVA IM administered at 0m, 2weeks, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. Receives: Biological: Anthrax Vaccine Adsorbed |
| Anthrax Vaccine Adsorbed 7-IM | Experimental | receive 7 injections of AVA IM administered at 0m, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. Receives: Biological: Anthrax Vaccine Adsorbed |
| Anthrax Vaccine Adsorbed 5-IM | Experimental | receive 5 injections of AVA IM administered at 0m, 1m, 6m, and 2 boosters - 30m and 42m. Receives: Biological: Anthrax Vaccine Adsorbed |
| Anthrax Vaccine Adsorbed 4-IM | Experimental | receive 4 injections of AVA IM; months 0, 2, 6 and a booster at month 42 Receives: Biological: Anthrax Vaccine Adsorbed |
| Saline placebo IM or SQ | Placebo comparator | Saline injections to be administered either IM or SQ at 0m, 2weeks, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. Receives: Biological: Saline injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local AEs
warmth, tenderness, itching, pain, arm motion limitation, erythema, induration, nodule, and bruise.
The number of injections analyzable varies for each event based on the presence or absence of reported data.
Measured: 4 weeks after each injection
Systemic AEs
Fatigue, Muscle Ache, Headache, Fever, Tender Axillary Lymphnode The number of injections analyzable varies for each event based on the presence or absence of reported data.
Measured: 4 weeks after each injection
Anti-protective Antigen IgG Geometric Mean Concentration
Geometric mean of the Anti-PA IgG Concentration measured in μg/mL. The lower limit of quantification (LLOQ) is 3.7, results below the LLOQ have been replaced by 1/2 LLOQ (1.85) before taking the geometric mean.
Measured: 4 weeks after the m1, m6 and m42 injections
Anti-protective Antigen IgG Geometric Mean Titer
Geometric mean of the Dilutional Titer. The Dilutional Titer is the reciprocal of the dilution at which the anti-PA IgG response reaches a threshold. The lower limit of quantification (LLOQ) is 58, results below the LLOQ have been replaced by 1/2 LLOQ (29) before taking the geometric mean.
Measured: 4 weeks after the m1, m6 and m42 injections
4-fold Rise in Anti-protective Antigen IgG Titer Response
Percent of participants who achieved a 4-fold or greater rise in anti-PA IgG Titer relative to the pre-vaccination level at month 0. The Dilutional Titer is the reciprocal of the dilution at which the anti-PA IgG response reaches a threshold. The lower limit of quantification (LLOQ) is 58, results below the LLOQ have been replaced by LLOQ (58) before calculating the fold response. Thus the lowest titer that can achieve 4-fold rise is 4*58 = 232.
Measured: 4 weeks after the m1, m6 and m42 injections
Secondary outcomes (1)
TNA ED50 Titer
Geometric mean of the ED50. The ED50 is the reciprocal of the dilution at which patient serum neutralizes 50% of a dose of anthrax lethal toxin (ED50). The lower limit of quantification (LLOQ) for this assay is 36, results below the LLOQ have been replaced with 1/2 LLOQ (18) before taking the geometric mean. Note that this secondary endpoint was only performed on ~47% of the participants.
Measured: 4 weeks after the m1, m6 and m42 injections
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2005 (estimated)
- Study startMay 2002
- Primary completionFeb 2010
- Study completionFeb 2010
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 (5)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,564 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Collaborators
- Walter Reed Army Institute of Research (WRAIR), Baylor College of Medicine, University of Alabama at Birmingham, Emory University, Mayo Clinic
- Responsible party
- Sponsor
- Investigators
- Jennifer Wright, DVM, Principal investigator, Centers for Disease Control and Prevention
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00119067
- Sponsor's protocol ID
- CDC-NCID-3344
- Acronym
- AVRP
- Status last verified
- May 2024
- First submitted
- 6 Jul 2005
- Last updated
- 29 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Marano N, Plikaytis BD, Martin SW, Rose C, Semenova VA, Martin SK, Freeman AE, Li H, Mulligan MJ, Parker SD, Babcock J, Keitel W, El Sahly H, Poland GA, Jacobson RM, Keyserling HL, Soroka SD, Fox SP, Stamper JL, McNeil MM, Perkins BA, Messonnier N, Quinn CP; Anthrax Vaccine Research Program Working Group. Effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial. JAMA. 2008 Oct 1;300(13):1532-43. doi: 10.1001/jama.300.13.1532.
PubMed 18827210Wright JG, Plikaytis BD, Rose CE, Parker SD, Babcock J, Keitel W, El Sahly H, Poland GA, Jacobson RM, Keyserling HL, Semenova VA, Li H, Schiffer J, Dababneh H, Martin SK, Martin SW, Marano N, Messonnier NE, Quinn CP. Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial. Vaccine. 2014 Feb 12;32(8):1019-28. doi: 10.1016/j.vaccine.2013.10.039. Epub 2013 Dec 25.
PubMed 24373307Quinn CP, Sabourin CL, Schiffer JM, Niemuth NA, Semenova VA, Li H, Rudge TL, Brys AM, Mittler RS, Ibegbu CC, Wrammert J, Ahmed R, Parker SD, Babcock J, Keitel W, Poland GA, Keyserling HL, El Sahly H, Jacobson RM, Marano N, Plikaytis BD, Wright JG. Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans. Clin Vaccine Immunol. 2016 Apr 4;23(4):326-38. doi: 10.1128/CVI.00696-15. Print 2016 Apr.
PubMed 26865594Falola MI, Wiener HW, Wineinger NE, Cutter GR, Kimberly RP, Edberg JC, Arnett DK, Kaslow RA, Tang J, Shrestha S. Genomic copy number variants: evidence for association with antibody response to anthrax vaccine adsorbed. PLoS One. 2013 May 31;8(5):e64813. doi: 10.1371/journal.pone.0064813. Print 2013.
PubMed 23741398Pajewski NM, Parker SD, Poland GA, Ovsyannikova IG, Song W, Zhang K, McKinney BA, Pankratz VS, Edberg JC, Kimberly RP, Jacobson RM, Tang J, Kaslow RA. The role of HLA-DR-DQ haplotypes in variable antibody responses to anthrax vaccine adsorbed. Genes Immun. 2011 Sep;12(6):457-65. doi: 10.1038/gene.2011.15. Epub 2011 Mar 3.
PubMed 21368772
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anthrax Vaccine Adsorbed: Human Reactogenicity and Immunogenicity Trial to Address Change in Route of Administration and Dose Reduction
- ClinicalTrials.gov ID
- NCT00119067
- Acronym / sponsor ID
- AVRP / CDC-NCID-3344
- Conditions
- Healthy
- Keywords
- Anthrax, Vaccine, Immunogenicity, Reactogenicity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,564 participants (actual)
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Collaborators
- Walter Reed Army Institute of Research (WRAIR), Baylor College of Medicine, University of Alabama at Birmingham, Emory University, Mayo Clinic
- Study start
- May 2002
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 13 Jul 2005 (estimated)
- Results
- Posted 29 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Anthrax Clinical Trial Objectives:
To assess whether:
- Anthrax vaccine (AVA or BioThrax, BioPort Corp. Lansing MI) administered by the intramuscular (IM) route elicits antibody responses that are not inferior (i.e., "non-inferior") to that achieved by the currently licensed schedule.
- BioThrax administered by the IM route and containing fewer numbers of doses elicits antibody responses that are not inferior (i.e., "non-inferior") to that achieved by the currently licensed schedule.
- Differences in reactogenicity exist between the IM and subcutaneous (SQ) administration of BioThrax.
Additionally for the final report we will assess whether:
- Occurrence of adverse events following AVA administration is influenced by selected risk factors.
Detailed description
This study is a 43-month prospective, randomized, double-blind, placebo-controlled comparison of immunogenicity and reactogenicity elicited by BioThrax given by different routes of administration (SQ versus IM) and dosing regimens (as many as 8 doses versus as few as 4 doses). Sterile saline is used as the placebo where doses are dropped in regimens using AVA, and in the all-placebo study group.
This study is conducted among a total of 1564 healthy adult men and women (18 to 61 years of age) at five sites in the United States. Participants were randomized into one of 6 study groups with 260 participants per group. One group receives BioThrax given as currently licensed (SQ with 6 doses followed by annual boosters); another group is given placebo IM (130 participants) or SQ (130 participants) in the currently licensed dosing regimen. The four other groups receive BioThrax IM in modified dosing regimens; placebo is given when a dose of BioThrax is omitted from the licensed dosing regimen. There are a total of 25 required visits for this study, during which all participants receive an injection of vaccine or placebo (8 injections total), have a blood sample drawn (16 or 17 total), and have an in-clinic examination for adverse events (22 total).
Immunogenicity is assessed by assaying 16 serial blood samples obtained from all participants and a 17th sample from a subset of participants before vaccination and at other specified times. Total anti-protective antigen IgG antibody (anti-PA IgG) is quantified using a standardized and validated enzyme-linked immunosorbent assay (ELISA); the primary study endpoints are 4-fold rise in antibody titer and antibody concentration relative to the pre-vaccination titers or assay reactivity threshold. A subset of serum samples is also assayed in an in vitro toxin neutralization assay (TNA) to measure the functional activity of anti-BioThrax antibodies. The kinetics of the immune response to BioThrax are examined at 3 time points in the study and blood samples from a subset of participants will be further tested in correlates of protection and immunogenetics substudies. All adverse events (AEs), including vaccine reactogenicity, are actively monitored. While all AEs will be ascertained among study participants, several endpoints will be defined based on the likelihood of their occurrence and/or their clinical importance. Of primary interest is the occurrence of local AEs such as warmth, tenderness, itching, pain, arm motion limitation, erythema, induration, nodule, and bruise. Systemic AEs such as fever, fatigue, muscle ache, headache, temperature, and painful axillary adenopathy are also evaluated.
This study is expected to provide the basis for consideration of change in route of BioThrax administration from SQ to IM and reduction in number of vaccine doses required for primary and booster immunization.
There is an interim analysis of data collected through each participant's first 7 months of this study for consideration in changing the route of BioThrax administration from SQ to IM, and elimination of the 2 week vaccine priming dose.
At the end of the study, the Sponsor will present the entire results of the trial to FDA for consideration in elimination of additional doses from the licensed BioThrax schedule. At that time, the Sponsor will also supplement these data with results from parallel non-human primate challenge studies and additional research on immunologic correlates of protection.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Anthrax Vaccine Adsorbed 8-SQ | Active comparator | Biological: Anthrax Vaccine Adsorbedreceive 8 injections of AVA injected SQ at the same points as the original licensure: 0m, 2weeks, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. |
| Anthrax Vaccine Adsorbed 8-IM | Experimental | Biological: Anthrax Vaccine Adsorbedreceive 8 injections of AVA IM administered at 0m, 2weeks, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. |
| Anthrax Vaccine Adsorbed 7-IM | Experimental | Biological: Anthrax Vaccine Adsorbedreceive 7 injections of AVA IM administered at 0m, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. |
| Anthrax Vaccine Adsorbed 5-IM | Experimental | Biological: Anthrax Vaccine Adsorbedreceive 5 injections of AVA IM administered at 0m, 1m, 6m, and 2 boosters - 30m and 42m. |
| Anthrax Vaccine Adsorbed 4-IM | Experimental | Biological: Anthrax Vaccine Adsorbedreceive 4 injections of AVA IM; months 0, 2, 6 and a booster at month 42 |
| Saline placebo IM or SQ | Placebo comparator | Biological: Saline injectionSaline injections to be administered either IM or SQ at 0m, 2weeks, 1m, 6m, 12m, 18m, and 2 boosters - 30m and 42m. |
Who may qualify
- Ages
- 18 to 61 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Read/sign Informed Consent Document; Female or male, 18 to 61 years old (up to 62nd birthday); Females must agree to exercise adequate birth control from the time of the screening procedures to one month after the last vaccination; willingness/ability to return for all follow-up visits and blood collections for the duration of the study; ability to understand/comply with planned study procedures; agree to complete the Participant Diary (Appendix G) and to report concomitant medications and AEs during the study period; thave two intact upper arms with sufficient subcutaneous and intramuscular tissue in the deltoid regions for vaccine administration.Potential participants with a history of the following conditions remain eligible for study enrollment: gestational diabetes; treated, controlled, uncomplicated hypertension; treated hypo- or hyperthyroidism; cured nonmetastatic cancer; disease-free for 5 years (excluding hematologic malignancies); localized skin cancer, resected (including squamous cell and basal cell carcinomas, participants with a history of melanoma must be disease-free for 5 years); exercise-induced bronchospasm; mild asthma: use of inhalers only for control of symptoms is acceptable (Persons who have required hospitalization for asthma within the previous 2 years or those who require chronic or frequent oral/parenteral steroids will not be eligible; use of low to medium doses of inhaled steroids; history of coronary artery disease, asymptomatic (NYHA Function Class I), on a stable medical regimen. Persons meeting these criteria must be at least 2 years post-myocardial infarction, cardiac bypass surgery, and/or percutaneous coronary intervention (e.g., angioplasty, stent placement, etc) in order to qualify. Persons with a history of cardiac disease must be under the care of a physician.
Key exclusion criteria (1 listed)
- Prior history of anthrax or immunization against anthrax; Known allergy to aluminum hydroxide, formaldehyde, benzethonium chloride, or latex; Pregnant/plans to become pregnant for duration of study/does not agree to use adequate birth control from the time of screening procedures to one month after last vaccination; Used cytotoxic therapy in previous 5 years; Cardiovascular disease with significant likelihood of progression over 5 years; Moderate to severe asthma, chronic obstructive pulmonary disease, other significant pulmonary disease; using high doses of inhaled steroids; Clinically recognized hepatic or renal insufficiency; Inflammatory, vasculitic, or rheumatic disease including systemic lupus erythematosis, polymyalgia rheumatica and rheumatoid arthritis, scleroderma; Known HIV, hepatitis B or hepatitis C infection; Other conditions known to produce or be associated with immune suppression; Neuropathy or other evolving neurologic condition; Unstable/moderate to severe mental illness; Ongoing drug abuse/dependence (including alcohol); Seizure disorder; Active malignancy or history of metastatic or hematologic malignancy; current diabetes; Anyone who plans to receive within 60 days of study entry: cytotoxic therapy, experimental products, a live vaccine outside this trial, immunosuppressive therapy, parenteral immunoglobulin or blood products; Anyone who plans to receive an inactivated vaccine outside this trial within 42 days after study entry;: experimental products, a live vaccine outside this trial, immunosuppressive therapy; Anyone who received an inactivated vaccine outside this trial within 14 days prior to study entry, parenteral immunoglobulin or blood products within three months of study. In addition to conditions listed above, temporary exclusion would result from moderate or severe illness and/or oral temperature >100.4˚F within 3 days of injection or chronic condition that, in opinion of investigator, would render injection unsafe or would interfere with evaluations.
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 |
|---|---|---|
| Anthrax Vaccine AdsorbedAlso: AVA, BioThrax | Biological | Anthrax Vaccine Adsorbed 4-IM, Anthrax Vaccine Adsorbed 5-IM, Anthrax Vaccine Adsorbed 7-IM, Anthrax Vaccine Adsorbed 8-IM, Anthrax Vaccine Adsorbed 8-SQ |
| Saline injection | Biological | Saline placebo IM or SQ |
Primary outcome
Local AEs
Time frame: 4 weeks after each injection
warmth, tenderness, itching, pain, arm motion limitation, erythema, induration, nodule, and bruise. The number of injections analyzable varies for each event based on the presence or absence of reported data.
Systemic AEs
Time frame: 4 weeks after each injection
Fatigue, Muscle Ache, Headache, Fever, Tender Axillary Lymphnode The number of injections analyzable varies for each event based on the presence or absence of reported data.
Anti-protective Antigen IgG Geometric Mean Concentration
Time frame: 4 weeks after the m1, m6 and m42 injections
Geometric mean of the Anti-PA IgG Concentration measured in μg/mL. The lower limit of quantification (LLOQ) is 3.7, results below the LLOQ have been replaced by 1/2 LLOQ (1.85) before taking the geometric mean.
Anti-protective Antigen IgG Geometric Mean Titer
Time frame: 4 weeks after the m1, m6 and m42 injections
Geometric mean of the Dilutional Titer. The Dilutional Titer is the reciprocal of the dilution at which the anti-PA IgG response reaches a threshold. The lower limit of quantification (LLOQ) is 58, results below the LLOQ have been replaced by 1/2 LLOQ (29) before taking the geometric mean.
4-fold Rise in Anti-protective Antigen IgG Titer Response
Time frame: 4 weeks after the m1, m6 and m42 injections
Percent of participants who achieved a 4-fold or greater rise in anti-PA IgG Titer relative to the pre-vaccination level at month 0. The Dilutional Titer is the reciprocal of the dilution at which the anti-PA IgG response reaches a threshold. The lower limit of quantification (LLOQ) is 58, results below the LLOQ have been replaced by LLOQ (58) before calculating the fold response. Thus the lowest titer that can achieve 4-fold rise is 4*58 = 232.
1 secondary outcome
TNA ED50 Titer
Time frame: 4 weeks after the m1, m6 and m42 injections
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18827210Marano N, Plikaytis BD, Martin SW, Rose C, Semenova VA, Martin SK, Freeman AE, Li H, Mulligan MJ, Parker SD, Babcock J, Keitel W, El Sahly H, Poland GA, Jacobson RM, Keyserling HL, Soroka SD, Fox SP, Stamper JL, McNeil MM, Perkins BA, Messonnier N, Quinn CP; Anthrax Vaccine Research Program Working Group. Effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial. JAMA. 2008 Oct 1;300(13):1532-43. doi: 10.1001/jama.300.13.1532.
- Results publication: PubMed 24373307Wright JG, Plikaytis BD, Rose CE, Parker SD, Babcock J, Keitel W, El Sahly H, Poland GA, Jacobson RM, Keyserling HL, Semenova VA, Li H, Schiffer J, Dababneh H, Martin SK, Martin SW, Marano N, Messonnier NE, Quinn CP. Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial. Vaccine. 2014 Feb 12;32(8):1019-28. doi: 10.1016/j.vaccine.2013.10.039. Epub 2013 Dec 25.
- Derived from this study: PubMed 26865594Quinn CP, Sabourin CL, Schiffer JM, Niemuth NA, Semenova VA, Li H, Rudge TL, Brys AM, Mittler RS, Ibegbu CC, Wrammert J, Ahmed R, Parker SD, Babcock J, Keitel W, Poland GA, Keyserling HL, El Sahly H, Jacobson RM, Marano N, Plikaytis BD, Wright JG. Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans. Clin Vaccine Immunol. 2016 Apr 4;23(4):326-38. doi: 10.1128/CVI.00696-15. Print 2016 Apr.
- Derived from this study: PubMed 23741398Falola MI, Wiener HW, Wineinger NE, Cutter GR, Kimberly RP, Edberg JC, Arnett DK, Kaslow RA, Tang J, Shrestha S. Genomic copy number variants: evidence for association with antibody response to anthrax vaccine adsorbed. PLoS One. 2013 May 31;8(5):e64813. doi: 10.1371/journal.pone.0064813. Print 2013.
- Derived from this study: PubMed 21368772Pajewski NM, Parker SD, Poland GA, Ovsyannikova IG, Song W, Zhang K, McKinney BA, Pankratz VS, Edberg JC, Kimberly RP, Jacobson RM, Tang J, Kaslow RA. The role of HLA-DR-DQ haplotypes in variable antibody responses to anthrax vaccine adsorbed. Genes Immun. 2011 Sep;12(6):457-65. doi: 10.1038/gene.2011.15. Epub 2011 Mar 3.
- 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.
Jennifer Wright, DVM principal investigator
Centers for Disease Control and Prevention
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Anthrax Vaccine Adsorbed and Saline injection in people with Healthy, run by Centers for Disease Control and Prevention at 5 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 1 inclusion and 1 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 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 29 May 2024). 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?
Local AEs (time frame: 4 weeks after each injection). The study lists 5 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 NCT00119067, which also lists 5 linked publications.
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 29 May 2024.