Anthrax AV7909 Liquid vs Lyophilized

NCT04660201 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 17-0093
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, parallel-group, double-blind, Phase 1 study designed to assess safety, tolerability and immunogenicity 2 formulations of adjuvanted anthrax vaccine (AV7909), lyophilized and liquid. Forty healthy young adults, 18 to 45 years old, inclusive, who meet all eligibility criteria, will be randomly allocated to one of two study groups in a 1:1 ratio: 20 will receive AV7909 as the thermostable lyophilized product and 20 will receive AV7909 as the liquid product. The vaccines will be given intramuscularly in a 2-dose schedule, 2 weeks apart. Safety will be assessed by evaluation of non-serious unsolicited Adverse Events, Serious Adverse Events (SAEs), Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs) \[the AESIs collected in this study are Potentially Immune-Mediated Medical Conditions (PIMMCs)\], and by laboratory evaluations. Reactogenicity will be measured by the occurrence of solicited injection site and systemic reactions in the week after each study vaccination. Immunogenicity testing will include performing serological assays to assess for toxin neutralizing antibodies (reported as ED50 and NF50), the gold standard assay for assessing response and protection following anthrax vaccines, prior to vaccination and on approximately Days 8, 15, 22, 29, 64, 195, and 380. In addition, anti-PA IgG antibodies will be measured by ELISA from the serum of participants, on those same days. The primary safety objective of this study is to assess the safety of lyophilized and liquid formulations of AV7909. The primary tolerability objective is to assess the tolerability of lyophilized and liquid formulations of AV7909.

Conditions

Anthrax; Anthrax Immunisation

Keywords

Anthrax; AV7909 (Liquid); Healthy Adult Volunteers; Immunogenicity; Phase 1; Safety; Thermostable AV7909 (Lyophilized); Vaccine

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Serious Adverse Events (SAEs).

  Serious adverse events (SAEs) included any AE or suspected adverse reaction that, in the view of either the site PI (or appropriate sub-investigator) or sponsor, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, was a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, was a congenital anomaly/birth defect, or may have jeopardized the participant and required medical or surgical intervention to prevent one of the aforementioned outcomes.

  Day 1 through Day 380

• Number of Participants With Abnormal Clinical Safety Laboratory Adverse Events (AEs).

  Clinical safety laboratory parameters include blood urea nitrogen (BUN), serum creatinine, alkaline phosphatase, alanine aminotransferase (ALT), total bilirubin, hemoglobin, hemoglobin decrease from baseline, white blood cell (WBC) count, absolute eosinophil count, absolute neutrophil count, platelets, aspartate aminotransferase (AST), random glucose, urine protein, and urine glucose.

  Day 29

• Number of Participants With Protocol-specified Adverse Events of Special Interest (AESIs)

  Adverse events of special interest (AESIs) in this study were potentially immune-mediated medical conditions (PIMMCs). A list of PIMMCs was provided in the study protocol, including gastrointestinal disorders, liver disorders, metabolic diseases, musculoskeletal disorders, neuroinflammatory disorders, skin disorders, vasculitides, and autoimmune syndromes.

  Day 1 through Day 380

• Number of Participants With Medically Attended Adverse Events (MAAEs).

  Adverse events (AEs) characterized by unscheduled medical attention, defined as hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel for any reason, were designated as medically attended adverse events (MAAEs).

  Day 1 through Day 380

• Number of Participants With Unsolicited, Non-serious Adverse Events (AEs).

  An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. The occurrence of an unsolicited AE may have come to the attention of study personnel during study visits and interviews for medical care, or upon review by a study monitor.

  Day 1 through Day 64

• Number of Participants With Solicited Injection Site and Systemic Reactogenicity Events Following First Study Vaccination.

  Injection site and systemic reactogenicity events were solicited daily throughout the week following each study vaccination. The number of participants reporting each event on any day following first vaccination is presented. Injection site reactogenicity events included pruritus, ecchymosis, erythema, edema/induration, pain, and tenderness. Systemic reactogenicity events included fever, feverishness, fatigue, malaise, myalgia, arthralgia, headache, and nausea.

  Day 1 through Day 8

• Number of Participants With Solicited Injection Site and Systemic Reactogenicity Events Following Second Study Vaccination.

  Injection site and systemic reactogenicity events were solicited daily throughout the week following each study vaccination. The number of participants reporting each event on any day following second vaccination is presented. Injection site reactogenicity events included pruritus, ecchymosis, erythema, edema/induration, pain, and tenderness. Systemic reactogenicity events included fever, feverishness, fatigue, malaise, myalgia, arthralgia, headache, and nausea.

  Day 15 through Day 22

Secondary Outcomes (7)

• Geometric Mean Titer (GMT) and 95% Confidence Interval (CI) of TNA ED50 (Toxin Neutralization Assay 50% Effective Dilution).

  Day 1, Day 8, Day 15, Day 22, Day 29, Day 64, Day 195, and Day 380

• Geometric Mean Titer (GMT) and 95% Confidence Interval (CI) of TNA NF50 (Toxin Neutralization Assay 50% Neutralization Factor).

  Day 1, Day 8, Day 15, Day 22, Day 29, Day 64, Day 195, and Day 380

• Geometric Mean Concentration (GMC) and 95% Confidence Interval (CI) of Anti-PA IgG (Anti-protective Antigen Immunoglobulin G)

  Day 1, Day 8, Day 15, Day 22, Day 29, Day 64, Day 195, and Day 380

• Percentage and 95% Confidence Interval (CI) of Participants Achieving TNA ED50 (Toxin Neutralization Assay 50% Effective Dilution) Seroconversion.

  Day 8, Day 15, Day 22, Day 29, Day 64, Day 195, and Day 380

• Percentage and 95% Confidence Interval (CI) of Participants Achieving TNA NF50 (Toxin Neutralization Assay 50% Neutralization Factor) Seroconversion.

  Day 8, Day 15, Day 22, Day 29, Day 64, Day 195, and Day 380

Study Arms (2)

Group 1

EXPERIMENTAL

AV7909 liquid formulation will be administered 0.5mL intramuscularly in a 2-dose schedule, 2 weeks apart (on Day 1 and Day 15). N=20

Biological: AV7909

Group 2

ACTIVE COMPARATOR

AV7909 lyophilized formulation will be administered 0.5mL intramuscularly in a 2-dose schedule, 2 weeks apart (on Day 1 and Day 15). N=20

Biological: AV7909

Interventions

AV7909 BIOLOGICAL

AV7909 (Liquid Formulation) is an investigational vaccine that is a preformulated, sterile, milky-white suspension for IM injection. It consists of the Anthrax Vaccine Adsorbed (AVA) bulk drug substance and CPG 7909 adjuvant

Group 1

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent prior to initiation of any study procedures.
• Understand and comply with planned study procedures, including completion of the electronic memory aid, and be available for all study visits.
• Agree to the collection of venous blood, per protocol.
• Have adequate venous access for phlebotomies.
• Be a male or non-pregnant female, 18 to 45 years of age, inclusive, at the time of enrollment.
• Be in good health.\*
• Have an oral temperature less than 100.0 degrees Fahrenheit.
• Have a pulse 51 to 100 beats per minute, inclusive.
• Have a systolic blood pressure 85 to 140 mmHg, inclusive.
• Have a diastolic blood pressure 55 to 90 mmHg, inclusive.
• Have a calculated body mass index (BMI) less than or equal to 35.0 kg/m2 at screening.
• Screening laboratories are within acceptable parameters:
• BUN \<23 mg/dL
• Serum creatinine (female) \<1.3 mg/dL
• Serum creatinine (male) \< 1.4 mg/dL

You may not qualify if:

• Have an acute illness\*, as determined by the site principal investigator (PI) or appropriate sub-investigator, within 72 hours prior to study vaccination.
• \*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters and systemic reactogenicity events as required by the protocol.
• Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation.\*
• \*Including acute, subacute, intermittent, or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of this trial.
• Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.\*
• Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
• Have known active or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. Non-melanoma treated skin cancers are permitted.
• Have known human immunodeficiency virus (HIV), chronic hepatitis B, or hepatitis C infection.
• Have known hypersensitivity or allergy to any components of the study vaccines (Anthrax Vaccine Adsorbed (AVA), CPG adjuvants, aluminum, benzethonium chloride \[phemerol\], formaldehyde).
• Have a history of receipt or plan to receive, while enrolled in this study, a licensed or unlicensed anthrax vaccine (except for the vaccines under study herein).
• Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).\*
• \*Adverse Events of Special Interest
• Have a history of alcohol or drug abuse within 5 years prior to study enrollment or test positive on the screening urine test for drugs of abuse.
• Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere\* with participant compliance or safety evaluations.
• \*As determined by the site PI or appropriate sub-investigator.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of Maryland, School of Medicine, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201-1509, United States

Location

MeSH Terms

Conditions

Anthrax

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: James Campbell, MD
• Organization: University of Maryland School of Medicine

Jcampbel@som.umaryland.edu

410-706-5328

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 9, 2020
• Study Start: May 25, 2022
• Primary Completion: November 1, 2023
• Study Completion: March 30, 2024
• Last Updated: December 19, 2024
• Results First Posted: December 19, 2024

Record last verified: 2020-09

Locations

US (1)