Anthrax Vaccine Clinical Trial to Assess Dose Reduction and Route Change

NCT00119067 | Completed Phase 4 Results DMC

• 1 other identifier: CDC-NCID-3344
• Study Type: interventional
• Target: 1,564
• Locations: 1 country
• Sites: 5

Brief 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.
• 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.

Conditions

Healthy

Keywords

Anthrax; Vaccine; Immunogenicity; Reactogenicity

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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 The lower limit of quantification (LLOQ) is 3.7, results below the LLOQ have been replaced by 1/2 LLOQ (1.85) before taking the geometric mean.

  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 The lower limit of quantification (LLOQ) is 58, results below the LLOQ have been replaced by 1/2 LLOQ (29) before taking the geometric mean.

  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.

  4 weeks after the m1, m6 and m42 injections

Secondary Outcomes (1)

• TNA ED50 Titer

  4 weeks after the m1, m6 and m42 injections

Study Arms (6)

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.

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.

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.

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.

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

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.

Biological: Saline injection

Interventions

Anthrax Vaccine Adsorbed BIOLOGICAL

Also known as: AVA, BioThrax

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

Eligibility Criteria

• Age: 18 Years - 61 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Walter Reed Army Institute of Research (WRAIR): collaborator
• Baylor College of Medicine: collaborator
• University of Alabama at Birmingham: collaborator
• Emory University: collaborator
• Mayo Clinic: collaborator

Study Sites (5)

University of Alabama, Birmingham (UAB)

Birmingham, Alabama, 35294-2050, United States

Location

Emory

Atlanta, Georgia, 30322, United States

Location

Walter Reed Army Institute for Research (WRAIR)

Silver Spring, Maryland, 20910-7500, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Baylor

Houston, Texas, 77030, United States

Location

Related Publications (5)

• 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.

  PMID: 18827210 BACKGROUND

• Wright 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.

  PMID: 24373307 RESULT

• Quinn 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.

  PMID: 26865594 DERIVED

• Falola 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.

  PMID: 23741398 DERIVED

• Pajewski 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.

  PMID: 21368772 DERIVED

MeSH Terms

Conditions

Anthrax

Interventions

Anthrax Vaccines; Biothrax; Sodium Chloride

Condition Hierarchy (Ancestors)

Bacillaceae Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

The study was not statistically powered to identify very rare SAEs.

Results Point of Contact

• Title: Jennifer G Wright
• Organization: CDC

jgwright@cdc.gov

Study Officials

• Jennifer Wright, DVM

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2005
• First Posted: July 13, 2005
• Study Start: May 1, 2002
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: May 29, 2024
• Results First Posted: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)