Plague, Plague, Pneumonic, Vaccine-Preventable Diseases
Conditions
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 (rF1V-1018) 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-1018 with a three-dose regimen of rF1V vaccine alone. The study will be conducted in 2 parts (Part 1 and Part 2).
Interventions
BIOLOGICALrF1V-1018
rF1V vaccine and CpG 1018® adjuvant
BIOLOGICALrF1V vaccine
rF1V vaccine
Sponsors
United States Department of Defense
Dynavax Technologies Corporation
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Reactogenicity and Safety | Day 1 to Week 56 | Rates of solicited local and systemic post-injection reactions, and AEs, severe AEs, SAEs, AESIs, and deaths |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rF1V-1018 Co-Administered rF1V vaccine and CpG 1018® adjuvant administered on Days 1 and 29, and 2 injections of placebo administered on Day 183 | 21 |
| rF1V-1018 Bedside Mix Bedside mix of rF1V vaccine and CpG 1018® adjuvant administered on Days 1 and 29, and 2 injections of placebo administered on Day 183 | 90 |
| rF1V Vaccine Only rF1V vaccine administered on Days 1, 29, and 183 | 89 |
| Total | 200 |
Baseline characteristics
| Characteristic | Total | rF1V-1018 Co-Administered | rF1V-1018 Bedside Mix | rF1V Vaccine Only |
|---|---|---|---|---|
| Age, Customized 18-39 | 100 Participants | 12 Participants | 42 Participants | 46 Participants |
| Age, Customized 40+ | 100 Participants | 9 Participants | 48 Participants | 43 Participants |
| Age, Customized Mean (SD) | 39.0 Years STANDARD_DEVIATION 9.76 | 39.1 Years STANDARD_DEVIATION 8.17 | 40.0 Years STANDARD_DEVIATION 9.2 | 37.9 Years STANDARD_DEVIATION 9.91 |
| Body mass index | 25.8 (kg/m^2) STANDARD_DEVIATION 3.04 | 26.5 (kg/m^2) STANDARD_DEVIATION 2.46 | 25.9 (kg/m^2) STANDARD_DEVIATION 3.04 | 25.5 (kg/m^2) STANDARD_DEVIATION 3.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 0 Participants | 8 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 175 Participants | 21 Participants | 77 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 0 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 1 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 43 Participants | 4 Participants | 19 Participants | 20 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 9 Participants | 1 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 138 Participants | 14 Participants | 62 Participants | 62 Participants |
| Sex: Female, Male Female | 79 Participants | 9 Participants | 34 Participants | 36 Participants |
| Sex: Female, Male Male | 121 Participants | 12 Participants | 56 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 90 | 1 / 89 |
| other Total, other adverse events | 18 / 21 | 77 / 90 | 69 / 89 |
| serious Total, serious adverse events | 1 / 21 | 0 / 90 | 3 / 89 |
Outcome results
Primary
Rates of Reactogenicity and Safety
Rates of solicited local and systemic post-injection reactions, and AEs, severe AEs, SAEs, AESIs, and deaths
Time frame: Day 1 to Week 56
Population: Safety analysis population: All participants who received at least 1 study injection and had any post-baseline safety data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rF1V-1018 Co-Administered | Rates of Reactogenicity and Safety | Local Reactions | 16 Participants |
| rF1V-1018 Co-Administered | Rates of Reactogenicity and Safety | Severe (Grade 3 or 4) AEs | 2 Participants |
| rF1V-1018 Co-Administered | Rates of Reactogenicity and Safety | Systemic Reactions | 13 Participants |
| rF1V-1018 Co-Administered | Rates of Reactogenicity and Safety | Severe Local Reactions | 0 Participants |
| rF1V-1018 Co-Administered | Rates of Reactogenicity and Safety | SAEs | 1 Participants |
| rF1V-1018 Co-Administered | Rates of Reactogenicity and Safety | At least 1 Unsolicited AE | 7 Participants |
| rF1V-1018 Co-Administered | Rates of Reactogenicity and Safety | Deaths | 0 Participants |
| rF1V-1018 Co-Administered | Rates of Reactogenicity and Safety | AESIs | 1 Participants |
| rF1V-1018 Co-Administered | Rates of Reactogenicity and Safety | Severe Systemic Reactions | 0 Participants |
| rF1V-1018 Bedside Mix | Rates of Reactogenicity and Safety | Severe Local Reactions | 0 Participants |
| rF1V-1018 Bedside Mix | Rates of Reactogenicity and Safety | SAEs | 0 Participants |
| rF1V-1018 Bedside Mix | Rates of Reactogenicity and Safety | AESIs | 0 Participants |
| rF1V-1018 Bedside Mix | Rates of Reactogenicity and Safety | Deaths | 0 Participants |
| rF1V-1018 Bedside Mix | Rates of Reactogenicity and Safety | Local Reactions | 67 Participants |
| rF1V-1018 Bedside Mix | Rates of Reactogenicity and Safety | Systemic Reactions | 60 Participants |
| rF1V-1018 Bedside Mix | Rates of Reactogenicity and Safety | Severe Systemic Reactions | 2 Participants |
| rF1V-1018 Bedside Mix | Rates of Reactogenicity and Safety | At least 1 Unsolicited AE | 27 Participants |
| rF1V-1018 Bedside Mix | Rates of Reactogenicity and Safety | Severe (Grade 3 or 4) AEs | 1 Participants |
| rF1V Vaccine Only | Rates of Reactogenicity and Safety | Deaths | 1 Participants |
| rF1V Vaccine Only | Rates of Reactogenicity and Safety | SAEs | 3 Participants |
| rF1V Vaccine Only | Rates of Reactogenicity and Safety | Severe Systemic Reactions | 0 Participants |
| rF1V Vaccine Only | Rates of Reactogenicity and Safety | AESIs | 1 Participants |
| rF1V Vaccine Only | Rates of Reactogenicity and Safety | Severe (Grade 3 or 4) AEs | 5 Participants |
| rF1V Vaccine Only | Rates of Reactogenicity and Safety | Severe Local Reactions | 2 Participants |
| rF1V Vaccine Only | Rates of Reactogenicity and Safety | Local Reactions | 57 Participants |
| rF1V Vaccine Only | Rates of Reactogenicity and Safety | At least 1 Unsolicited AE | 28 Participants |
| rF1V Vaccine Only | Rates of Reactogenicity and Safety | Systemic Reactions | 42 Participants |