Yellow Fever
Conditions
Keywords
HydroVax, Yellow Fever virus, dose-ranging, double blind, Placebo-Controlled, Vaccine
Brief summary
This trial will be a randomized, placebo controlled, double-blind (within dosing group), dose escalation Phase 1 trial, evaluating dosages of 1 mcg and 5 mcg of HydroVax-002 YFV vaccine given intramuscularly on Day 1 and Day 29 in up to 25 healthy adults healthy adults ≥ 18 and \< 50 years of age. The primary objective is to assess the safety, reactogenicity, and tolerability of the HydroVax-002 YFV vaccine administered intramuscularly in a two-dose series on Days 1 and 29 at a dose of 1 mcg or a dose of 5 mcg.
Detailed description
This trial will be a randomized, placebo controlled, double-blind (within dosing group), dose escalation Phase 1 trial evaluating dosages of 1 mcg and 5 mcg of HydroVax-002 YFV vaccine given intramuscularly on Day 1 (the day of first vaccination is defined as Day 1) and Day 29 in healthy adults ≥ 18 and \< 50 years of age. The study will consist of two dosing groups of HydroVax-002 YFV vaccine to be enrolled sequentially. Each dose group will consist of 10 individuals who receive HydroVax-002 YFV, as well as 5 total subjects who receive placebo. Each dose-group will include a sentinel subgroup consisting of 3 vaccine and 1 placebo recipient. In each of the two (1 mcg and 5 mcg) dose phases, enrollment is halted after the dose 1 vaccination of the sentinel subgroup. Following assessment of safety and reactogenicity data of Group 1 by the Safety Monitoring Committee (SMC), the vaccine dose will be increased to 5 mcg for Group 2.
Interventions
BIOLOGICALHydroVax-002 YFV
Inactivated YFV vaccine
OTHERPlacebo
NaCl 0.9%, Normal Saline
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Najit Technologies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provide written informed consent prior to initiation of any study procedures. 2. Are able to understand and comply with planned study procedures and be available for all study visits. 3. Must agree to the collection of venous blood per protocol. 4. Are males or non-pregnant females, ≥18 and \<50 years of age, inclusive at time of enrollment. 5. Are in good health\*. \*As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical or psychiatric diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, emergency room or urgent care for condition, or invasive medical procedure and no adverse symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication, dose or in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening or treatment of continued symptoms of medical diagnosis or condition. Note: Low dose topical, corticosteroids as outlined in the Subject
Exclusion criteria
(see below) as well as herbals, vitamins and supplements are permitted. 6. Oral temperature is less than 100.0°F. 7. Pulse is 47 to 100 beats per minute, inclusive. 8. Systolic blood pressure is 85 to 140 mmHg, inclusive. 9. Diastolic blood pressure is 55 to 90 mmHg, inclusive. 10. Screening laboratories (WBC, Hgb, PLTs, Sodium, Potassium, Bicarbonate, Calcium, Cr, non-fasting glucose, ALT, AST, TBIL and urine protein and glucose) are within acceptable parameters\*. \*Hematology, blood chemistry and liver enzymes must be Grade 1 or less at screening; urine glucose and protein negative at screening for subjects to qualify for randomization and vaccination. 11. Negative test for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) at screening blood draw. 12. Women of childbearing potential\* must use an acceptable contraception method† from at least 30 days before the first study vaccination until 30 days after the second study vaccination. \*Not sterilized via, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure® placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \<1 year has passed since the last menses if menopausal. †Includes non-male sexual relationships, full abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more and shown to be azoospermic prior to the subject receiving the study vaccination, effective intrauterine devices, NuvaRing®, tubal ligation, and licensed hormonal methods such as implants, injectables or oral contraceptives (i.e. the pill). 13. Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to each study vaccination. 14. Sexually active males must agree to use a medically acceptable form of contraception\* in order to be in this study and must agree to continue such use until day 30 after the last vaccination. \*Medically acceptable contraceptives include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicide. Contraceptive measures such as Plan B™, sold for emergency use after unprotected sex, are not acceptable methods for routine use.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Any AE Through Day 29 After the Second Vaccination | Through day 29 after the second vaccination |
| Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Through 7 days after each vaccination |
| Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Through 7 days after each vaccination |
| Occurrence of All Serious Adverse Events (SAEs) at Any Time During the Study | Day 1 post first vaccination to Day 180 post second vaccination |
| Occurrence of All Grade 3 Unsolicited Adverse Events (AEs) From First Vaccination Through Day 29 After the Second Vaccination | Through day 29 after the second vaccination |
| Occurrence of All Grade 3 Laboratory Toxicities From First Vaccination Through Day 15 After the Second Vaccination | Through day 15 after the second vaccination |
Secondary
| Measure | Time frame |
|---|---|
| Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | At days 15 and 29 after first vaccination and at days 15, 29, 57, and 180 following second vaccination |
| Percentage of Subjects Achieving Seroconversion (Greater Than or Equal to 1:10 in Plaque Reduction Neutralizing Titer [PRNT50] Titer) at Day 29 After First Vaccination and at Day 29 After Second Vaccination | At day 29 after first vaccination and at day 29 after second vaccination |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose 1 mcg intramuscularly (IM) of HydroVax-002 YFV on Days 1 and 29. | 10 |
| High Dose 5 mcg intramuscularly (IM) of HydroVax-002 YFV on Days 1 and 29. | 10 |
| Placebo Placebo intramuscularly (IM) on Days 1 and 29. | 6 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Low Dose | Total | Placebo | High Dose |
|---|---|---|---|---|
| Age, Continuous | 35.9 years STANDARD_DEVIATION 8.3 | 32.8 years STANDARD_DEVIATION 8.1 | 34.7 years STANDARD_DEVIATION 8.6 | 28.7 years STANDARD_DEVIATION 6.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 26 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 25 Participants | 6 Participants | 10 Participants |
| Region of Enrollment United States | 10 participants | 26 participants | 6 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 11 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 15 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 5 |
| other Total, other adverse events | 6 / 10 | 7 / 10 | 5 / 5 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 5 |
Outcome results
Primary
Occurrence of All Grade 3 Laboratory Toxicities From First Vaccination Through Day 15 After the Second Vaccination
Time frame: Through day 15 after the second vaccination
Population: One placebo subject was excluded from analysis (Did not receive vaccination).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Occurrence of All Grade 3 Laboratory Toxicities From First Vaccination Through Day 15 After the Second Vaccination | Related | 0 Grade 3 Laboratory Toxicities |
| Low Dose | Occurrence of All Grade 3 Laboratory Toxicities From First Vaccination Through Day 15 After the Second Vaccination | Unrelated | 0 Grade 3 Laboratory Toxicities |
| High Dose | Occurrence of All Grade 3 Laboratory Toxicities From First Vaccination Through Day 15 After the Second Vaccination | Related | 0 Grade 3 Laboratory Toxicities |
| High Dose | Occurrence of All Grade 3 Laboratory Toxicities From First Vaccination Through Day 15 After the Second Vaccination | Unrelated | 0 Grade 3 Laboratory Toxicities |
| Placebo | Occurrence of All Grade 3 Laboratory Toxicities From First Vaccination Through Day 15 After the Second Vaccination | Related | 0 Grade 3 Laboratory Toxicities |
| Placebo | Occurrence of All Grade 3 Laboratory Toxicities From First Vaccination Through Day 15 After the Second Vaccination | Unrelated | 1 Grade 3 Laboratory Toxicities |
Primary
Occurrence of All Grade 3 Unsolicited Adverse Events (AEs) From First Vaccination Through Day 29 After the Second Vaccination
Time frame: Through day 29 after the second vaccination
Population: One placebo subject was excluded from analysis (Did not receive vaccination).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Occurrence of All Grade 3 Unsolicited Adverse Events (AEs) From First Vaccination Through Day 29 After the Second Vaccination | Related | 0 Grade 3 Unsolicited Adverse Event |
| Low Dose | Occurrence of All Grade 3 Unsolicited Adverse Events (AEs) From First Vaccination Through Day 29 After the Second Vaccination | Unrelated | 0 Grade 3 Unsolicited Adverse Event |
| High Dose | Occurrence of All Grade 3 Unsolicited Adverse Events (AEs) From First Vaccination Through Day 29 After the Second Vaccination | Related | 0 Grade 3 Unsolicited Adverse Event |
| High Dose | Occurrence of All Grade 3 Unsolicited Adverse Events (AEs) From First Vaccination Through Day 29 After the Second Vaccination | Unrelated | 0 Grade 3 Unsolicited Adverse Event |
| Placebo | Occurrence of All Grade 3 Unsolicited Adverse Events (AEs) From First Vaccination Through Day 29 After the Second Vaccination | Related | 0 Grade 3 Unsolicited Adverse Event |
| Placebo | Occurrence of All Grade 3 Unsolicited Adverse Events (AEs) From First Vaccination Through Day 29 After the Second Vaccination | Unrelated | 0 Grade 3 Unsolicited Adverse Event |
Primary
Occurrence of All Serious Adverse Events (SAEs) at Any Time During the Study
Time frame: Day 1 post first vaccination to Day 180 post second vaccination
Population: One placebo subject was excluded from analysis (Did not receive vaccination).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Occurrence of All Serious Adverse Events (SAEs) at Any Time During the Study | 0 Serious Adverse Event |
| High Dose | Occurrence of All Serious Adverse Events (SAEs) at Any Time During the Study | 0 Serious Adverse Event |
| Placebo | Occurrence of All Serious Adverse Events (SAEs) at Any Time During the Study | 0 Serious Adverse Event |
Primary
Occurrence of Any AE Through Day 29 After the Second Vaccination
Time frame: Through day 29 after the second vaccination
Population: One placebo subject was excluded from analysis (Did not receive vaccination).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one local solicited adverse event | 4 Adverse Event |
| Low Dose | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one systemic solicited adverse event | 6 Adverse Event |
| Low Dose | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one related unsolicited adverse event | 0 Adverse Event |
| Low Dose | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one unrelated unsolicited adverse event | 6 Adverse Event |
| High Dose | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one unrelated unsolicited adverse event | 7 Adverse Event |
| High Dose | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one local solicited adverse event | 7 Adverse Event |
| High Dose | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one related unsolicited adverse event | 0 Adverse Event |
| High Dose | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one systemic solicited adverse event | 4 Adverse Event |
| Placebo | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one unrelated unsolicited adverse event | 5 Adverse Event |
| Placebo | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one systemic solicited adverse event | 3 Adverse Event |
| Placebo | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one related unsolicited adverse event | 0 Adverse Event |
| Placebo | Occurrence of Any AE Through Day 29 After the Second Vaccination | At least one local solicited adverse event | 1 Adverse Event |
Primary
Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination
Time frame: Through 7 days after each vaccination
Population: One subject in the low dose group withdrew prior to the second vaccination. One placebo subject was excluded from analysis (Did not receive vaccination).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 0 | 0 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 1 | 1 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 2 | 0 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 3 | 0 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 4 | 0 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 5-7 | 0 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 0 | 0 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 1 | 3 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 2 | 1 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 3 | 1 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 4 | 1 Solicited Local Adverse Event |
| Low Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 5-7 | 0 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 5-7 | 0 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 0 | 1 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 0 | 0 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 2 | 1 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 1 | 4 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 5-7 | 0 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 4 | 0 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 2 | 3 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 1 | 3 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 4 | 0 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 3 | 0 Solicited Local Adverse Event |
| High Dose | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 3 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 3 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 4 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 3 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 5-7 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 0 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 1 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 4 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 0 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 1 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 2 | 1 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 1, Day 2 | 0 Solicited Local Adverse Event |
| Placebo | Occurrence of Solicited Local AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Local Symptom, Post-Dose 2, Day 5-7 | 0 Solicited Local Adverse Event |
Primary
Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination
Time frame: Through 7 days after each vaccination
Population: One subject in the low dose group withdrew prior to the second vaccination. One placebo subject was excluded from analysis (Did not receive vaccination).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 0 | 0 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 1 | 3 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 2 | 1 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 3 | 0 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 4 | 2 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 5-7 | 2 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 0 | 0 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 1 | 1 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 2 | 1 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 3 | 1 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 4 | 0 Solicited Systemic Adverse Event |
| Low Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 5-7 | 3 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 5-7 | 1 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 0 | 1 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 0 | 0 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 2 | 2 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 1 | 1 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 5-7 | 0 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 4 | 1 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 2 | 1 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 1 | 2 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 4 | 0 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 3 | 0 Solicited Systemic Adverse Event |
| High Dose | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 3 | 1 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 3 | 0 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 4 | 0 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 3 | 1 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 5-7 | 0 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 0 | 0 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 1 | 1 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 4 | 0 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 0 | 0 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 1 | 1 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 2 | 0 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 1, Day 2 | 0 Solicited Systemic Adverse Event |
| Placebo | Occurrence of Solicited Systemic AE and Reactogenicity Signs and Symptoms in the 7 Days After Each Vaccination | Any Systemic Symptom, Post-Dose 2, Day 5-7 | 0 Solicited Systemic Adverse Event |
Secondary
Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination
Time frame: At days 15 and 29 after first vaccination and at days 15, 29, 57, and 180 following second vaccination
Population: One low dose subject withdrew prior to the second vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Low Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 15 Post Dose 1 | 5.00 PRNT50 GMT |
| Low Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 29 Post Dose 1 | 5.74 PRNT50 GMT |
| Low Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 15 Post Dose 2 | 7.35 PRNT50 GMT |
| Low Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 29 Post Dose 2 | 7.35 PRNT50 GMT |
| Low Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 57 Post Dose 2 | 6.80 PRNT50 GMT |
| Low Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 180 Post Dose 2 | 5.83 PRNT50 GMT |
| High Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 180 Post Dose 2 | 5.00 PRNT50 GMT |
| High Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 15 Post Dose 1 | 5.00 PRNT50 GMT |
| High Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 29 Post Dose 2 | 6.60 PRNT50 GMT |
| High Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 57 Post Dose 2 | 5.74 PRNT50 GMT |
| High Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 29 Post Dose 1 | 5.74 PRNT50 GMT |
| High Dose | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 15 Post Dose 2 | 6.16 PRNT50 GMT |
| Placebo | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 29 Post Dose 1 | 5.00 PRNT50 GMT |
| Placebo | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 15 Post Dose 2 | 5.00 PRNT50 GMT |
| Placebo | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 180 Post Dose 2 | 5.00 PRNT50 GMT |
| Placebo | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 29 Post Dose 2 | 5.00 PRNT50 GMT |
| Placebo | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 15 Post Dose 1 | 5.00 PRNT50 GMT |
| Placebo | Geometric Mean Neutralizing Titers at Days 15 and 29 After First Vaccination and at Days 15, 29, 57, and 180 Following Second Vaccination | Day 57 Post Dose 2 | 5.00 PRNT50 GMT |
Secondary
Percentage of Subjects Achieving Seroconversion (Greater Than or Equal to 1:10 in Plaque Reduction Neutralizing Titer [PRNT50] Titer) at Day 29 After First Vaccination and at Day 29 After Second Vaccination
Time frame: At day 29 after first vaccination and at day 29 after second vaccination
Population: One low dose subject withdrew prior to the second vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Percentage of Subjects Achieving Seroconversion (Greater Than or Equal to 1:10 in Plaque Reduction Neutralizing Titer [PRNT50] Titer) at Day 29 After First Vaccination and at Day 29 After Second Vaccination | Day 29 Post Dose 1 | 10.0 percentage of participants |
| Low Dose | Percentage of Subjects Achieving Seroconversion (Greater Than or Equal to 1:10 in Plaque Reduction Neutralizing Titer [PRNT50] Titer) at Day 29 After First Vaccination and at Day 29 After Second Vaccination | Day 29 Post Dose 2 | 22.2 percentage of participants |
| High Dose | Percentage of Subjects Achieving Seroconversion (Greater Than or Equal to 1:10 in Plaque Reduction Neutralizing Titer [PRNT50] Titer) at Day 29 After First Vaccination and at Day 29 After Second Vaccination | Day 29 Post Dose 1 | 10.0 percentage of participants |
| High Dose | Percentage of Subjects Achieving Seroconversion (Greater Than or Equal to 1:10 in Plaque Reduction Neutralizing Titer [PRNT50] Titer) at Day 29 After First Vaccination and at Day 29 After Second Vaccination | Day 29 Post Dose 2 | 20.0 percentage of participants |
| Placebo | Percentage of Subjects Achieving Seroconversion (Greater Than or Equal to 1:10 in Plaque Reduction Neutralizing Titer [PRNT50] Titer) at Day 29 After First Vaccination and at Day 29 After Second Vaccination | Day 29 Post Dose 1 | 0.0 percentage of participants |
| Placebo | Percentage of Subjects Achieving Seroconversion (Greater Than or Equal to 1:10 in Plaque Reduction Neutralizing Titer [PRNT50] Titer) at Day 29 After First Vaccination and at Day 29 After Second Vaccination | Day 29 Post Dose 2 | 0.0 percentage of participants |