BARDA Securing Anthrax Immunity For the Elderly

NCT03518125 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: BP-C-17001HHSO100201400004I
• Study Type: interventional
• Target: 305
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Anthrax

Keywords

Anthrax; Bacillaceae Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Anthrax Vaccine Adsorbed; BioThrax; AV7909; CPG 7909; Adjuvant; Vaccines; Post-exposure Prophylaxis

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Day 64

Secondary Outcomes (12)

• Treatment-emergent Unsolicited Adverse Events (AEs)

  Day 1 through Day 394

• Treatment-emergent Serious Adverse Events (SAEs)

  Day 1 through Day 394

• Treatment-emergent Medically Attended Adverse Events (MAAEs)

  Day 1 through Day 394

• Treatment-emergent Potentially Immune Mediated Medical Conditions (PIMMCs)

  Day 1 through Day 394

• Solicited Local Reactogenicity Symptoms on the Contralateral Arm

  Day 1-8, Day 15-22, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)

Study Arms (6)

Age ≥ 66, BioThrax (Days 1, 15, 29)

EXPERIMENTAL

Subjects dosed on Days 1, 15, and 29 with 0.5 mL BioThrax.

Biological: BioThrax

Age ≥ 66, AV7909 (Days 1, 15, 29)

EXPERIMENTAL

Subjects dosed on Days 1, 15, and 29 with 0.5 mL AV7909.

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.

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.

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.

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.

Biological: AV7909; Drug: Sodium chloride injection USP, 0.9% (placebo)

Interventions

BioThrax BIOLOGICAL

Other Names: Anthrax Vaccine Adsorbed (AVA)

Age ≥ 66, BioThrax (Days 1, 15, 29); Age18-50, BioThrax (Days 1, 15, 29)

AV7909 BIOLOGICAL

Anthrax Vaccine Absorbed plus CPG 7909 Adjuvant

Also known as: AV7909 Anthrax Vaccine Adsorbed, NuThrax

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) DRUG

Other Names: Saline Solution

Age 18-50, AV7909 (Days 1 and 15); Age ≥ 66, AV7909 (Days 1 and 15); Age ≥ 66, AV7909 (Days 1 and 29)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.
• 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.
• 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 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.

Sponsors & Collaborators

• Biomedical Advanced Research and Development Authority: lead
• Rho, Inc.: collaborator

Study Sites (4)

Johnson County Clin-Trials

Lenexa, Kansas, 66219, United States

Location

Coastal Carolina Research Center

Mt. Pleasant, South Carolina, 29464, United States

Location

Clinical Research Associates, Inc.

Nashville, Tennessee, 29464, United States

Location

JBR Clinical Research

Salt Lake City, Utah, 84124, United States

Location

Related Publications (1)

• 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.

  PMID: 33129609 DERIVED

MeSH Terms

Conditions

Anthrax; Bacillaceae Infections; Gram-Positive Bacterial Infections; Bacterial Infections

Interventions

Biothrax

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Susan Hollingsworth/Regulatory Operations Specialist
• Organization: BARDA

Susan.Hollingsworth@hhs.gov

202-691-2040

Study Officials

• Carlos Fierro, MD

  Johnson County Clin-Trials

  PRINCIPAL INVESTIGATOR

• Derek Muse, MD

  JBR Clinical Research

  PRINCIPAL INVESTIGATOR

• Stephan Sharp, MD

  Clinical Research Associates, Inc.

  PRINCIPAL INVESTIGATOR

• Cynthia Strout, MD

  Coastal Carolina Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 24, 2018
• First Posted: May 8, 2018
• Study Start: May 9, 2018
• Primary Completion: January 14, 2019
• Study Completion: December 9, 2019
• Last Updated: July 21, 2020
• Results First Posted: June 9, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)