PA83-FhCMB Plant-Derived Recombinant Protective Antigen (rPA) Anthrax Vaccine

A Phase 1 Study of the Safety and Immunogenicity of Plant-Derived Recombinant Protective Antigen (rPA) Anthrax Vaccine in Healthy Adults

The purposes of this study is to evaluate and compare the safety, reactogenicity, and tolerability of the PA83-FhCMB vaccine candidate delivered at 4 dose levels with Alhydrogel

Study Overview

• Status: Completed
• Conditions: Anthrax
• Intervention / Treatment: Biological: PA83-FhCMB

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Walter Reed Army Institute of Research, Clinical Trials Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Citizen or permanent resident of the US
• Male or female aged 18 to 49 years inclusive
• Able to give written informed consent
• Healthy, as determined by medical history, physical examination, vital signs, and clinical safety laboratory examinations at baseline

• Females should fulfill one of the following criteria:

  1. At least one year post-menopausal
  2. Surgically sterile
  3. Willing to use a medically approved form of contraception (eg, oral, implantable, transdermal, or injectable hormonal contraceptive; intrauterine device; barrier protection to include female condom, diaphragm, cervical cap, or male condoms in conjunction with spermicide) for 30 days prior to first vaccination and through the end of the study
  4. Willing to abstain from sexual intercourse for 30 days prior to first vaccination and through the end of the study
• Women of childbearing potential must have a negative urine pregnancy test within 24 hours preceding receipt of each dose
• Comprehension of the study requirements
• Expressed availability for the required study period
• Ability to attend scheduled visits and to be contacted by telephone throughout the follow-up period

Exclusion Criteria:

• History of anthrax disease or receipt of anthrax vaccine
• Presence of significant uncontrolled medical or psychiatric illness (acute or chronic) including institution of new medical or surgical treatment or a significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months of screening
• Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies
• Pregnancy or lactation
• Cancer or treatment for cancer, within the previous 3 years, excluding basal cell carcinoma
• Presence of any medical condition that may be associated with impaired immune responsiveness, including diabetes mellitus, per the investigator's discretion

• Presently receiving or history of receiving, during the preceding 3-month period, any medications or other treatments that may adversely affect the immune system

  1. This includes allergy injections, immune globulin, interferon, immunomodulators, cytotoxic drugs, or systemic corticosteroids (oral or injectable; 20 mg/day x 14 days or longer)
  2. Radiation therapy
  3. Intranasal and topical corticosteroids will be allowed
• Receipt or planned administration of a non study vaccine within 14 days prior to vaccination and throughout the study period (30 days for live vaccines) Immunization on an emergency basis with Tetanus Toxoids Adsorbed for adult use (Td or Tdap) or influenza vaccine up to 14 days before or at least 14 days after a dose of study vaccine will be allowed
• History of anaphylactic type reaction to injected vaccines
• History of drug or chemical abuse in the year before the study
• Receipt of any investigational product or nonregistered drug within 30 days prior to vaccination or currently enrolled in any investigational drug study or intends to enroll in such a study within the ensuing study period
• Receipt of blood or blood products 8 weeks prior to vaccination or planned administration during the study period
• Donation of blood or blood products within 8 weeks prior to vaccination or at any time during the study

• Acute disease within 72 hours prior to vaccination

  1. Acute disease is defined as the presence of a moderate or severe illness (as determined by the Investigator through medical history and physical examination) with or without fever (≥38°C; 100.4°F), or an oral temperature of ≥38°C orally
  2. Study vaccine can be administered to persons with a minor illness
• History of immunodeficiency, chronic illness requiring continuous or frequent medical intervention, autoimmune disease, use of immunosuppressive medications, or ongoing therapy with systemic corticosteroids within 3 months prior to any planned vaccine dose. Inhaled and topical steroids are permitted. "Burst" therapy of steroids is permitted except within 2 weeks prior to vaccination.
• Evidence of psychiatric, medical and/or substance abuse problems during the past 6 months that the investigator believes would adversely affect the subject's ability to participate in the trial

• Occupational or other responsibilities that would prevent completion of participation in the trial, including:

  1. US military or reservists who may receive the licensed anthrax vaccine (BioThrax) or served during the Persian Gulf War between January and May, 1991. Such individuals may be enrolled only if they provide their medical records, which can then show proof that they have not received the licensed anthrax vaccine.
  2. Postal and other workers who may be exposed to anthrax or may have to take BioThrax
• Any condition that, in the opinion of the investigator, might interfere with interpretation of data supporting the primary study objectives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 12.5 µg + Alhydrogel; vaccine	Biological: PA83-FhCMB
Experimental: 25 µg + Alhydrogel; vaccine	Biological: PA83-FhCMB
Experimental: 50 µg + Alhydrogel; vaccine	Biological: PA83-FhCMB
Experimental: 100 µg + Alhydrogel; vaccine	Biological: PA83-FhCMB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in antibody titer after three immunizations	Up to 6 months

Collaborators and Investigators

• Sponsor: Fraunhofer, Center for Molecular Biotechnology

Publications and helpful links

General Publications

• Paolino KM, Regules JA, Moon JE, Ruck RC, Bennett JW, Remich SA, Mills KT, Lin L, Washington CN, Fornillos GA, Lindsey CY, O'Brien KA, Shi M, Mark Jones R, Green BJ, Tottey S, Chichester JA, Streatfield SJ, Yusibov V. Safety and immunogenicity of a plant-derived recombinant protective antigen (rPA)-based vaccine against Bacillus anthracis: A Phase 1 dose-escalation study in healthy adults. Vaccine. 2022 Mar 15;40(12):1864-1871. doi: 10.1016/j.vaccine.2022.01.047. Epub 2022 Feb 10.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: August 13, 2014
• First Submitted That Met QC Criteria: September 10, 2014
• First Posted (Estimate): September 12, 2014

Study Record Updates

• Last Update Posted (Estimate): May 12, 2016
• Last Update Submitted That Met QC Criteria: May 10, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Bacillaceae Infections; Anthrax
• Other Study ID Numbers: FhCMB rPA83-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED