Trial Outcomes & Findings for Trial of Yellow Fever Inactivated Vaccine (NCT NCT00995865)

Last Updated: 2016-05-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

60 participants

Primary outcome timeframe

Measured from 0 up to 21 Days

Results posted on

2016-05-05

Participant Flow

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.

60 Subjects enrolled in this study. 3 Subjects discontinued in this study.

Participant milestones

Participant milestones
Measure	High Dose XRX-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	Mid Dose XRX-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	Placebo NaCl Injectable 0.9% Placebo: NaCl Injectable 0.9%
Overall Study STARTED	24	24	12
Overall Study COMPLETED	22	24	11
Overall Study NOT COMPLETED	2	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	High Dose XRX-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	Mid Dose XRX-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	Placebo NaCl Injectable 0.9% Placebo: NaCl Injectable 0.9%
Overall Study Protocol Violation	2	0	0
Overall Study Lost to Follow-up	0	0	1

Baseline Characteristics

Trial of Yellow Fever Inactivated Vaccine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High Dose Group n=22 Participants 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).	Mid-Dose Group n=24 Participants 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.	Placebo Group n=11 Participants This third group of 12 subjects were to receive a placebo (0.9% normal saline for injection).	Total n=57 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	24 Participants n=7 Participants	11 Participants n=5 Participants	57 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	34 years STANDARD_DEVIATION 10.0 • n=5 Participants	31 years STANDARD_DEVIATION 9.1 • n=7 Participants	29 years STANDARD_DEVIATION 8.2 • n=5 Participants	32 years STANDARD_DEVIATION 9.3 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	10 Participants n=7 Participants	6 Participants n=5 Participants	25 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	14 Participants n=7 Participants	5 Participants n=5 Participants	32 Participants n=4 Participants
Region of Enrollment United States	22 participants n=5 Participants	24 participants n=7 Participants	11 participants n=5 Participants	57 participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	High Dose Group n=24 Participants XRX-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. 24 Subjects were examined in this group.	Mid Dose Group n=24 Participants XRX-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	Placebo Group n=12 Participants Subjects were administered with NaCl Injectable 0.9%. 12 Subjects were examined in this 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	13 participants	2 participants
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	21 participants	10 participants
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	19 participants	4 participants
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	21 participants	10 participants
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	1 participants	0 participants
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	4 participants	3 participants
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	2 participants	3 participants
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	8 participants	7 participants
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	2 participants	5 participants
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	0 participants	1 participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	High Dose Group n=24 Participants XRX-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. 24 Subjects were examined in this group.	Mid Dose Group n=24 Participants XRX-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	Placebo Group n=12 Participants Subjects were administered with NaCl Injectable 0.9%. 12 Subjects were examined in this 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	8 participants	0 participants
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	10 participants	0 participants
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	16 participants	7 participants
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	16 participants	7 participants
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	2 participants	3 participants
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	4 participants	5 participants
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	6 participants	5 participants
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	3 participants	3 participants
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	3 participants	3 participants
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	2 participants	1 participants
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	4 participants	4 participants
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	3 participants	3 participants
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	5 participants	3 participants
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	2 participants	0 participants

SECONDARY outcome

Timeframe: 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.

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;

Outcome measures

Outcome measures
Measure	High Dose Group n=22 Participants XRX-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. 24 Subjects were examined in this group.	Mid Dose Group n=24 Participants XRX-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	Placebo Group n=11 Participants Subjects were administered with NaCl Injectable 0.9%. 12 Subjects were examined in this 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 Interval 85.0 to 100.0	71 Percentage of subjects Interval 49.0 to 87.0	0 Percentage of subjects Interval 0.0 to 29.0
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 Interval 24.0 to 68.0	13 Percentage of subjects Interval 3.0 to 32.0	0 Percentage of subjects Interval 0.0 to 29.0
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 Interval 14.0 to 55.0	13 Percentage of subjects Interval 3.0 to 32.0	0 Percentage of subjects Interval 0.0 to 29.0
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 Interval 85.0 to 100.0	88 Percentage of subjects Interval 68.0 to 97.0	0 Percentage of subjects Interval 0.0 to 29.0
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 Interval 85.0 to 100.0	75 Percentage of subjects Interval 53.0 to 90.0	0 Percentage of subjects Interval 0.0 to 29.0
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 Interval 85.0 to 100.0	88 Percentage of subjects Interval 68.0 to 97.0	0 Percentage of subjects Interval 0.0 to 29.0

SECONDARY outcome

Timeframe: 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.