Yellow Fever
Conditions
Keywords
Prevention of yellow fever virus infection
Brief summary
The Phase 1 trial is a single-center, randomized, double blind, placebo-controlled, dose-ranging out-patient study designed to provide the first clinical data on the safety, tolerability and immunogenicity of XRX-001 inactivated yellow fever vaccine in 60 healthy male and female volunteers, 18-49 years of age. Subjects will receive two inoculations of one of two dose levels of XRX-001 vaccine. A control group will receive placebo. Safety will be determined by the incidence and severity of adverse events in each treatment group and in the combined cohorts in the double blind treatment period up to 42 days post-vaccination. Subjects will also be followed-up at 3, 6 and 12 months to determine severe adverse events (SAEs) and changes in health status. Efficacy will be assessed by neutralizing antibody response to the vaccine. The co-primary immunogenicity endpoints will be the dose-response analysis of seroconversion rates (fourfold or greater increase in neutralizing antibody titer between baseline and Day 42) and of the 50% plaque reduction neutralization test (PRNT50) geometric mean titers (GMT) at Day 42. Secondary immunogenicity endpoints will include: 1. The seroconversion rates and GMT neutralizing antibody titers for all dose groups combined on Days 21 and 42. 2. The reverse cumulative distribution curve of antibody titers on Days 21 and 42 for each dose group and for all dose groups combined 3. The duration of antibody titers displaying the seroconversion rate and GMT across all time-points to Month 12, by treatment group and for both dose groups combined.
Interventions
BIOLOGICALXRX-001 Inactivated yellow fever vaccine
Inactivated yellow fever vaccine, alum adsorbed, High dose = 2.3 x 10\^8 VE/0.5mL and Mid dose = 2.2 x 10\^7 VE/0.5mL
BIOLOGICALPlacebo
NaCl Injectable 0.9%
Sponsors
GE Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* All aspects of the protocol explained and written informed consent obtained from the subject; * Aged 18 to 49 years, inclusive; * In good general health, without significant medical history, physical examination findings, or abnormal laboratory results; and * Subject must be available for the study duration, including all planned follow-up visits. * For female subjects of child bearing potential: Negative serum pregnancy tests at Day -7 to -1, and negative urine pregnancy tests prior to vaccination on Days 0, in conjunction with a menstrual and contraceptive history indicating a low probability of pregnancy in the opinion of the physician. Females of childbearing potential will be required to be correctly using an efficacious hormonal method of contraception or intrauterine device for at least 1 month before randomization and during the on-study phase to Day 42. Barrier methods of contraception will not be considered acceptable for study entry. Female subjects of child-bearing potential will acknowledge by signing their informed consent that contraception will be correctly practised during the specified periods and will specify the method used. Female subjects unable to become pregnant must have this documented (e.g. tubal ligation, hysterectomy or postmenopausal \[at least one year since last menstrual period\]).
Exclusion criteria
* History of travel to South America or SubSaharan Africa; * History of active duty military service; * History of vaccination against yellow fever, tick-borne encephalitis (TBE), or Japanese encephalitis; * Went to primary (grade) school in Austria, Germany, Japan, South Korea, India, Thailand, Nepal, Vietnam, or Taiwan (where TBE vaccination is practiced) * History of dengue fever; * Known or suspected immunodeficiency disorder, including leukemia, lymphoma, generalized malignancy, or treatment with immunosuppressive medications, including corticosteroids, alkylating agents, antimetabolites, or radiation therapy. Low dose steroids (≤ 10 mg prednisone or equivalent, topical or intra-articular/bursal/tendon/epidural injections of corticosteroids) do not constitute a reason for exclusion; * History of an autoimmune disorder, including systemic lupus, rheumatoid arthritis, scleroderma, other collagen vascular disease, multiple sclerosis, etc. Psoriasis limited to cutaneous manifestations is not an exclusion criterion; * Prior history of anaphylaxis to foods, hymenoptera stings, vaccines or drugs; * Transfusion of blood or treatment with any blood product, including intramuscular or intravenous serum globulin within 3 months of the Screening Visit or anticipated up to Study Day 42; * Administration of another vaccine within 30 days preceding the screening visit or anticipated up to Day 42 (these subjects may be rescheduled for vaccination at a later date); * Participation in another clinical trial within 60 days of the screening visit; * Positive serum or urine pregnancy test prior to vaccination (women of child-bearing potential or lactation or intended pregnancy during study period); * Abnormalities on laboratory assessment (i.e. meeting the criteria defined for a mild, moderate or severe adverse event in Appendix 1, a1A); * Seropositive to HIV or HCV or positive for HBsAg; * Physical examination indicating any clinically significant medical condition; * Body temperature \>38.1°C (100.6°F) or acute illness within 3 days prior to vaccination (subject may be rescheduled); * Intention to travel out of the area prior to the study visit on Day 42; * History of excessive alcohol consumption, drug abuse, significant psychiatric illness; and * Intention to increase normal exercise routine, participate in contact sports or strenuous weight lifting or to initiate vigorous exercise from Screening until after Day 42.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Measured from 0 up to 21 Days | Subjects were observed for 60 minutes (greater than of equal to 60 minutes and less than of equal to 90 minutes) after vaccine adminstration for any signs or symptoms or local and/or systematic intolerance to the test articles and vital signs were to be checked within the same observation timeframe. After vaccination, subjects were to complete a memory aid to record daily temperature, symptoms, and concomitant medications from Day-0 to Day-42. Subjects were to return to the clinic on Days 3, 10, 21, 24, 31, and 42 with a second vaccination given on Day 21. At each visit, study personnel were to conduct a structured adverse event (AE) interview, and subject were to use their memory aid to assist with the recall of symptoms experiences and daily oral temperatures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Days 21 and 42, 12 months | Secondary immunogenicity endpoints will use 2 dose levels of XRX-001 inactivated yellow fever vaccine determined by 50% plaque reduction neutralization test (PRNT50). Dose groups were to be compared for neutralizing antibody seroconverison rate, distribution of antibody titers, and geometric mean antibody titers (GMTs) to yellow fever 17D virus. The seroconversion rates and GMT neutralizing antibody titers for each dose group and all dose groups combined; The reverse cumulative distribution curve of antibody titers; |
| Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. | GMT titers measured at days 21, 31 and 42 for different dose rates. | Geometric mean antibody titers (GMT) neutralizing antibody titers for each dose groups. |
Countries
United States
Participant flow
Recruitment details
2 of the Subjects in the High-Dose made it thru the study, however, it was later found that those 2 subjects vaccinated prior to joining this study. One (1) subject in the Placebo went thru the the study, but was later lost to follow-up.
Pre-assignment details
60 Subjects enrolled in this study. 3 Subjects discontinued in this study.
Participants by arm
| Arm | Count |
|---|---|
| High Dose Group Two groups of 24 subjects each, (one arm called a high dose group, the other a Mid-Dose group) were to receive two intramuscular (IM) injections (0.5mL) of XRX-001 vaccine containing either greater than or equal to 8.0 log10 VE/dose (viral equivalent) (high dose) or 1/10th of the high dose for the (mid dose). | 22 |
| Mid-Dose Group Two groups of 24 subjects each were to receive two intramuscular (IM) injections (0.5mL) of XRX-001 vaccine containing either greater than or equal to 8.0 log10 VE/dose (viral equivalent) (high dose) or 1/10th of the high dose for this (mid dose) group. | 24 |
| Placebo Group This third group of 12 subjects were to receive a placebo (0.9% normal saline for injection). | 11 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Mid-Dose Group | Placebo Group | High Dose Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 11 Participants | 22 Participants | 57 Participants |
| Age, Continuous | 31 years STANDARD_DEVIATION 9.1 | 29 years STANDARD_DEVIATION 8.2 | 34 years STANDARD_DEVIATION 10 | 32 years STANDARD_DEVIATION 9.3 |
| Region of Enrollment United States | 24 participants | 11 participants | 22 participants | 57 participants |
| Sex: Female, Male Female | 10 Participants | 6 Participants | 9 Participants | 25 Participants |
| Sex: Female, Male Male | 14 Participants | 5 Participants | 13 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 24 | 24 / 24 | 12 / 12 | 24 / 24 | 24 / 24 | 12 / 12 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 12 | 0 / 24 | 0 / 24 | 0 / 12 |
Outcome results
Primary
The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination.
Subjects were observed for 60 minutes (greater than of equal to 60 minutes and less than of equal to 90 minutes) after vaccine adminstration for any signs or symptoms or local and/or systematic intolerance to the test articles and vital signs were to be checked within the same observation timeframe. After vaccination, subjects were to complete a memory aid to record daily temperature, symptoms, and concomitant medications from Day-0 to Day-42. Subjects were to return to the clinic on Days 3, 10, 21, 24, 31, and 42 with a second vaccination given on Day 21. At each visit, study personnel were to conduct a structured adverse event (AE) interview, and subject were to use their memory aid to assist with the recall of symptoms experiences and daily oral temperatures.
Time frame: Measured from 0 up to 21 Days
Population: Subjects were to return to the clinic on Days 3,10, 21, 24, 31,and 42 with the second vaccination given on Day 21. At each visit, study personnel were to conduct a structured adverse event (AE) interview, and subject were to use their memory aid to assist with the recall of symptoms experiences and daily oral temperatures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Pain | 13 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Redness | 22 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Tenderness | 15 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Swelling | 22 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Itching | 3 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Diarrhea | 0 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Malaise | 4 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Headache | 2 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Tiredness | 7 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Nausea | 3 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Tiredness | 2 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Pain | 13 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Diarrhea | 4 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Itching | 1 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Redness | 21 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Nausea | 0 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Headache | 8 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Tenderness | 19 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Malaise | 2 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Swelling | 21 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Headache | 7 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Swelling | 10 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Itching | 0 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Diarrhea | 3 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Tiredness | 5 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Malaise | 3 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Pain | 2 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Nausea | 1 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Redness | 10 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 0-21 (1st injection)-Tenderness | 4 participants |
Primary
The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination.
Subjects were observed for 60 minutes (greater than of equal to 60 minutes and less than of equal to 90 minutes) after vaccine adminstration for any signs or symptoms or local and/or systematic intolerance to the test articles and vital signs were to be checked within the same observation timeframe. After vaccination, subjects were to complete a memory aid to record daily temperature, symptoms, and concomitant medications from Day-0 to Day-42. Subjects were to return to the clinic on Days 3, 10, 21, 24, 31, and 42 with a second vaccination given on Day 21. At each visit, study personnel were to conduct a structured adverse event (AE) interview, and subject were to use their memory aid to assist with the recall of symptoms experiences and daily oral temperatures.
Time frame: Measured from 22 up to 42 Days.
Population: Subjects were to combined at days 22 to 42 . At each visit, study personnel were to conduct a structured adverse event (AE) interview, and subject were to use their memory aid to assist with the recall of symptoms experiences and daily oral temperatures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Tiredness | 2 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Malaise | 1 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Redness | 12 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Chills | 0 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Headache | 1 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Tenderness | 8 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Feverishness | 0 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Muscle Ache | 0 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Nausea | 1 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Swelling | 12 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Shortness of Breath | 0 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Pain | 6 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Vomiting | 1 participants |
| High Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Drowsiness | 1 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Tiredness | 4 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Pain | 8 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Tenderness | 10 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Redness | 16 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Swelling | 16 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Vomiting | 2 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Malaise | 4 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Headache | 6 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Muscle Ache | 3 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Feverishness | 3 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Chills | 2 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Nausea | 3 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Drowsiness | 5 participants |
| Mid Dose Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Shortness of Breath | 2 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Drowsiness | 3 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Chills | 1 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Vomiting | 3 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Swelling | 7 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Tiredness | 4 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Redness | 7 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Pain | 0 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Nausea | 3 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Tenderness | 0 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Muscle Ache | 3 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Headache | 5 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Shortness of Breath | 0 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Feverishness | 3 participants |
| Placebo Group | The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. | Days 22-42 (2nd injection)-Malaise | 5 participants |
Secondary
Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus.
Geometric mean antibody titers (GMT) neutralizing antibody titers for each dose groups.
Time frame: GMT titers measured at days 21, 31 and 42 for different dose rates.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High Dose Group | Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. | Geometric mean titer Day 31--10 Days after 2nd Inj | 146 Geometric Antibody titers |
| High Dose Group | Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. | Geometric mean titer Day 21--21 Days 1st Inj) | 10 Geometric Antibody titers |
| High Dose Group | Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. | Geometric mean titer Day 42--21 Days after 2nd Inj | 113 Geometric Antibody titers |
| Mid Dose Group | Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. | Geometric mean titer Day 31--10 Days after 2nd Inj | 39 Geometric Antibody titers |
| Mid Dose Group | Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. | Geometric mean titer Day 21--21 Days 1st Inj) | 6 Geometric Antibody titers |
| Mid Dose Group | Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. | Geometric mean titer Day 42--21 Days after 2nd Inj | 30 Geometric Antibody titers |
| Placebo Group | Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. | Geometric mean titer Day 21--21 Days 1st Inj) | 5 Geometric Antibody titers |
| Placebo Group | Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. | Geometric mean titer Day 42--21 Days after 2nd Inj | 5 Geometric Antibody titers |
| Placebo Group | Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus. | Geometric mean titer Day 31--10 Days after 2nd Inj | 5 Geometric Antibody titers |
Secondary
Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001
Secondary immunogenicity endpoints will use 2 dose levels of XRX-001 inactivated yellow fever vaccine determined by 50% plaque reduction neutralization test (PRNT50). Dose groups were to be compared for neutralizing antibody seroconverison rate, distribution of antibody titers, and geometric mean antibody titers (GMTs) to yellow fever 17D virus. The seroconversion rates and GMT neutralizing antibody titers for each dose group and all dose groups combined; The reverse cumulative distribution curve of antibody titers;
Time frame: Days 21 and 42, 12 months
Population: Seropositive was to show a significant level of serum antibodies, or other immunologic marker in the serum, indicating previous exposure to the infectious agent being tested. In immunology, seroconversion is the time period during which a specific antibody develops and becomes detectable in the blood.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seropositive-Day 21(21 Days after 1st Injection) | 46 Percentage of subjects |
| High Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Serocovert-Day 21 (21 Days after 1st Injection) | 32 Percentage of subjects |
| High Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seropositivity-Day 31 (10 Days after second Inj) | 100 Percentage of subjects |
| High Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seroconvert- Day 31 (10 Days after second Inj) | 100 Percentage of subjects |
| High Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seropositivity -Day 42 (21 Days after 2nd Inj) | 100 Percentage of subjects |
| High Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seroconvert-Day 42 (21 Days after 2nd Inj) | 100 Percentage of subjects |
| Mid Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seroconvert-Day 42 (21 Days after 2nd Inj) | 71 Percentage of subjects |
| Mid Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seropositive-Day 21(21 Days after 1st Injection) | 13 Percentage of subjects |
| Mid Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seroconvert- Day 31 (10 Days after second Inj) | 75 Percentage of subjects |
| Mid Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seropositivity -Day 42 (21 Days after 2nd Inj) | 88 Percentage of subjects |
| Mid Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Serocovert-Day 21 (21 Days after 1st Injection) | 13 Percentage of subjects |
| Mid Dose Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seropositivity-Day 31 (10 Days after second Inj) | 88 Percentage of subjects |
| Placebo Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Serocovert-Day 21 (21 Days after 1st Injection) | 0 Percentage of subjects |
| Placebo Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seropositivity-Day 31 (10 Days after second Inj) | 0 Percentage of subjects |
| Placebo Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seroconvert-Day 42 (21 Days after 2nd Inj) | 0 Percentage of subjects |
| Placebo Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seroconvert- Day 31 (10 Days after second Inj) | 0 Percentage of subjects |
| Placebo Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seropositive-Day 21(21 Days after 1st Injection) | 0 Percentage of subjects |
| Placebo Group | Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001 | Seropositivity -Day 42 (21 Days after 2nd Inj) | 0 Percentage of subjects |