Trial of the Immunogenicity, Safety, and Tolerability of rF1V Vaccine With CpG 1018® Adjuvant Compared With rF1V Vaccine in Adults 18 to 55 Years of Age

Study Overview
=================
Brief Summary
-----------------
Phase 2, Randomized, Active-Controlled, Observer-Blinded, Multicenter Trial of the Immunogenicity, Safety, and Tolerability of rF1V Vaccine with CpG 1018® Adjuvant Compared with rF1V Vaccine in Adults 18 to 55 Years of Age

Detailed Description
-----------------
Phase 2, randomized, active-controlled, observer-blind, multicenter trial of the immunogenicity, safety, and tolerability of rF1V vaccine with CpG 1018® adjuvant compared with rF1V vaccine alone in adults. Approximately two hundred healthy adults 18 to 55 years of age will be enrolled to compare a two-dose regimen of rF1V vaccine with CpG 1018® adjuvant administered on study Days 1 and 29 (and placebo at Day 183) with a three-dose regimen of rF1V vaccine alone administered on study Days 1, 29, and 183. The study will be conducted in 2 parts (Part 1 and Part 2).

Official Title
-----------------
Phase 2, Randomized, Active-Controlled, Observer-Blinded, Multicenter Trial of the Immunogenicity, Safety, and Tolerability of rF1V Vaccine With CpG 1018® Adjuvant Compared With rF1V Vaccine in Adults 18 to 55 Years of Age

Conditions
-----------------
Plague, Pneumonic, Plague, Vaccine-Preventable Diseases

Intervention / Treatment
-----------------
* Biological: rF1V vaccine and CpG 1018® adjuvant
* Biological: rF1V vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults aged 18 to 55 years Healthy participants or participants with pre-existing medical conditions who are in a stable medical condition. Pre-existing stable medical condition means a subject who: has full capacity of daily activity and no major medication modification within 3 months prior to Day 1; has not undergone surgical or minimally-invasive intervention or had any hospitalization/emergency room visit for the specific medical condition. Able to comply with the protocol schedule and procedures. Able and willing to provide written informed consent If female of child-bearing potential and heterosexually active, has practiced adequate contraception for 28 days prior to vaccination and has negative pregnancy tests just prior to vaccination and has agreed to continue adequate contraception until 28 days after last study injection. Adequate contraception is defined as a contraceptive method with a failure rate of < 1% per year when used consistently and correctly and, when applicable, in accordance with the product label. Examples include the following: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal Progestin-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable Intrauterine device (IUD) with or without hormonal release Vasectomized partner, provided he is the subject's sole partner and that he has received a medical assessment of the surgical success Credible self-reported history of heterosexual abstinence for at least 28 days prior to vaccine administration Female partner Exclusion Criteria: A history of plague disease or have previously received any plague vaccine. Active tuberculosis or other systemic infectious process. History of human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) infection, or positive test for antibody to HIV, HBV, or HCV History of autoimmune disorder History of sensitivity to any component of study vaccines Body mass index ≥ 30 kg/m2 Has received the following prior to the injection: 14 days: COVID-19 vaccine Any inactivated vaccine 28 days: Any live vaccine Systemic corticosteroids (more than 3 consecutive days) or other immunomodulators or immunomodulators immune suppressive medication, with the exception of inhaled steroids Any other investigational medicinal agent 90 days: Immunoglobulins or any blood products Granulocyte or granulocyte-macrophage colony-stimulating factor Antisense oligonucleotides Drugs/investigational agents with very long half-lives (defined as ≥ 60 days) At any time: DNA plasmids or other genetic therapy intended to integrate permanently into host cells If female is pregnant (known before or established at the time of screening), breastfeeding, or planning a pregnancy Is undergoing chemotherapy or expected to receive chemotherapy during the study period; has a diagnosis of cancer within the last 5 years other than squamous cell or basal cell carcinoma of the skin History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator Oral temperature >100.0°F at the time of vaccine administration. History of acute myocardial infarction (AMI) or documented coronary artery disease (CAD)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Group 1:rF1V vaccine and CpG 1018® adjuvant co-administered<br>rF1V vaccine and CpG 1018® adjuvant will be administered on Days 1 and 29, and 2 injections of placebo will be administered on Day 183 | Biological: rF1V vaccine and CpG 1018® adjuvant<br>* rF1V vaccine and CpG 1018® adjuvant<br>|
| Experimental: Part 1 Group 2:rF1V vaccine and CpG 1018® adjuvant bedside mix<br>Bedside mix of rF1V vaccine and CpG 1018® adjuvant and placebo will be administered on Days 1 and 29, and 2 injections of placebo will be administered on Day 183 | Biological: rF1V vaccine and CpG 1018® adjuvant<br>* rF1V vaccine and CpG 1018® adjuvant<br>|
| Active Comparator: Part 1 Group 3: rF1V vaccine and placebo<br>rF1V vaccine and placebo will be administered on Days 1, 29, and 183 | Biological: rF1V vaccine<br>* rF1V vaccine<br>|
| Experimental: Part 2 Group 1 & 3, OR Group 2 & 3<br>Group 1 & 3 (if selected): Group 1: rF1V vaccine and CpG 1018® adjuvant will be administered on Days 1 and 29, and 2 injections of placebo will be administered on Day 183. Group 3: rF1V vaccine and placebo will be administered on Days 1, 29, and 183 OR Group 2 & 3 (if selected): Group 2: Bedside mix of rF1V vaccine and CpG 1018® adjuvant will be administered on Days 1 and 29; placebo will be administered on Day 183. Group 3: rF1V vaccine will be administered on Days 1, 29, and 183 | Biological: rF1V vaccine and CpG 1018® adjuvant<br>* rF1V vaccine and CpG 1018® adjuvant<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Select one method of administration of rF1V vaccine with CpG 1018® adjuvant for Part 2 | To select one of the two methods of administration of rF1V vaccine with CpG 1018® adjuvant for Part 2 by comparing humoral immunization response 28 days after the second dose of vaccine | 28 days after second dose of vaccine of last participant in part 1 | 
| Assess the utility of a 2-dose schedule of rF1V vaccine with CpG 1018® adjuvant | To assess the utility of a 2-dose schedule of rF1V vaccine with CpG 1018® adjuvant as measured by reduction in time to onset of predicted rF1V protection | Through day 211 in part 2 | 
| Assess the serum Bridge ELISA concentration to rF1V vaccine with CpG 1018® adjuvant compared with rF1V vaccine 28 days after the second dose of vaccine |  | 28 days after second dose of vaccine of last participant in part 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of rF1V vaccine with CpG 1018® adjuvant compared with rF1V vaccine as measured by rates of reactogenicity and adverse events using grading system in CBER's toxicity guidance document. |  | Through week 50 | 
| To assess the serum Bridge ELISA concentration to rF1V vaccine with CpG 1018® adjuvant at selected time points after each dose |  | Week 0, 4, 8, 12, 16, 30, 38, 50 |