Trial Outcomes & Findings for A Prospective Study to Evaluate the Safety of a New Monovalent Intranasal Influenza Vaccine (NCT NCT00873912)
NCT ID: NCT00873912
Last Updated: 2011-07-14
Results Overview
The percentage of subjects with fever was compared between the two treatment groups based on the upper limit of the two-sided 95% exact confidence interval (CI) for the rate difference (monovalent vaccine minus placebo). The upper limit of the two-sided 95% CI was evaluated against the pre-specified equivalence criterion of 5 percentage points which corresponded to the following hypotheses: - H0 (null): rate difference ≥ 5 percentage points, - HA (alternative): rate difference \< 5 percentage points.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
300 participants
Primary outcome timeframe
Days 1-8 after vaccination
Results posted on
2011-07-14
Participant Flow
A total of 300 subjects were randomized into the study between 26May2009 and 27May2009 at 3 sites in the USA.
Each site enrolled and randomized 80 subjects in the monovalent vaccine group and 20 subjects in the placebo group
Participant milestones
| Measure |
Monovalent Influenza Virus Vaccine
Frozen monovalent vaccine containing the new strain was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10\^7 fluorescent focus units (FFU) of influenza virus type B/Brisbane/60/2008 (Victoria lineage). A single dose of investigational product was administered on Day 1.
|
Placebo
Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer and egg allantoic fluid. A single dose of investigational product was administered on Day 1.
|
|---|---|---|
|
Overall Study
STARTED
|
240
|
60
|
|
Overall Study
COMPLETED
|
237
|
60
|
|
Overall Study
NOT COMPLETED
|
3
|
0
|
Reasons for withdrawal
| Measure |
Monovalent Influenza Virus Vaccine
Frozen monovalent vaccine containing the new strain was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10\^7 fluorescent focus units (FFU) of influenza virus type B/Brisbane/60/2008 (Victoria lineage). A single dose of investigational product was administered on Day 1.
|
Placebo
Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer and egg allantoic fluid. A single dose of investigational product was administered on Day 1.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
Baseline Characteristics
A Prospective Study to Evaluate the Safety of a New Monovalent Intranasal Influenza Vaccine
Baseline characteristics by cohort
| Measure |
Monovalent Influenza Virus Vaccine
n=240 Participants
Frozen monovalent vaccine containing the new strain was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10\^7 fluorescent focus units (FFU) of influenza virus type B/Brisbane/60/2008 (Victoria lineage). A single dose of investigational product was administered on Day 1.
|
Placebo
n=60 Participants
Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer and egg allantoic fluid. A single dose of investigational product was administered on Day 1.
|
Total
n=300 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
32.2 years
STANDARD_DEVIATION 8.1 • n=5 Participants
|
30.9 years
STANDARD_DEVIATION 8.6 • n=7 Participants
|
31.9 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
124 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
157 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
116 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
143 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
36 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
204 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
254 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
7 participants
n=5 Participants
|
2 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
18 participants
n=5 Participants
|
5 participants
n=7 Participants
|
23 participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
206 participants
n=5 Participants
|
50 participants
n=7 Participants
|
256 participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 participants
n=5 Participants
|
1 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race (NIH/OMB)
Other
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
240 participants
n=5 Participants
|
60 participants
n=7 Participants
|
300 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Days 1-8 after vaccinationPopulation: The Safety Population includes all subjects who received at least one dose of investigational product and experienced any follow-up for safety. Treatment group was assigned based on the actual investigational product received.
The percentage of subjects with fever was compared between the two treatment groups based on the upper limit of the two-sided 95% exact confidence interval (CI) for the rate difference (monovalent vaccine minus placebo). The upper limit of the two-sided 95% CI was evaluated against the pre-specified equivalence criterion of 5 percentage points which corresponded to the following hypotheses: - H0 (null): rate difference ≥ 5 percentage points, - HA (alternative): rate difference \< 5 percentage points.
Outcome measures
| Measure |
Monovalent Influenza Virus Vaccine
n=240 Participants
Frozen monovalent vaccine containing the new strain was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10\^7 fluorescent focus units (FFU) of influenza virus type B/Brisbane/60/2008 (Victoria lineage). A single dose of investigational product was administered on Day 1.
|
Placebo
n=60 Participants
Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer and egg allantoic fluid. A single dose of investigational product was administered on Day 1.
|
|---|---|---|
|
Number of Participants Reporting Fever, Defined as Oral Temperature ≥ 101°F
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Days 1-8 after vaccinationPopulation: The Safety Population includes all subjects who received at least one dose of investigational product and experienced any follow-up for safety. Treatment group was assigned based on the actual investigational product received.
Solicited symptoms were collected from administration of investigational product through Study Day 15. For this study, solicited symptoms included: fever (\> 100°F oral), runny nose, sore throat, cough, vomiting, muscle aches, chills, decreased activity (tiredness), headache.
Outcome measures
| Measure |
Monovalent Influenza Virus Vaccine
n=240 Participants
Frozen monovalent vaccine containing the new strain was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10\^7 fluorescent focus units (FFU) of influenza virus type B/Brisbane/60/2008 (Victoria lineage). A single dose of investigational product was administered on Day 1.
|
Placebo
n=60 Participants
Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer and egg allantoic fluid. A single dose of investigational product was administered on Day 1.
|
|---|---|---|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Any solicited symptom
|
97 participants
|
23 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Fever > 100°F
|
2 participants
|
1 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Fever ≥ 101°F
|
1 participants
|
1 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Fever > 102°F
|
0 participants
|
0 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Fever > 103°F
|
0 participants
|
0 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Runny nose
|
66 participants
|
10 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Sore throat
|
33 participants
|
4 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Cough
|
10 participants
|
3 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Vomiting
|
1 participants
|
1 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Muscle aches
|
15 participants
|
4 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Chills
|
0 participants
|
0 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Decreased activity (tiredness)
|
18 participants
|
2 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Headache
|
42 participants
|
11 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One Adverse Event (AE)
Total participants reporting ≥ one AE
|
27 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Days 1-15 after vaccinationPopulation: The Safety Population includes all subjects who received at least one dose of investigational product and experienced any follow-up for safety. Treatment group was assigned based on the actual investigational product received.
Outcome measures
| Measure |
Monovalent Influenza Virus Vaccine
n=240 Participants
Frozen monovalent vaccine containing the new strain was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10\^7 fluorescent focus units (FFU) of influenza virus type B/Brisbane/60/2008 (Victoria lineage). A single dose of investigational product was administered on Day 1.
|
Placebo
n=60 Participants
Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer and egg allantoic fluid. A single dose of investigational product was administered on Day 1.
|
|---|---|---|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Any solicited symptom
|
102 participants
|
25 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Fever > 100°F
|
3 participants
|
1 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Fever ≥ 101°F
|
1 participants
|
1 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Fever > 103°F
|
0 participants
|
0 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Runny nose
|
68 participants
|
11 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Sore throat
|
38 participants
|
4 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Cough
|
13 participants
|
3 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Vomiting
|
1 participants
|
1 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Muscle aches
|
16 participants
|
4 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Chills
|
1 participants
|
0 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Headache
|
44 participants
|
13 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Total participants reporting ≥ one AE
|
29 participants
|
3 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Fever > 102°F
|
0 participants
|
0 participants
|
|
Number of Participants Reporting Any Solicited Symptom or at Least One AE
Decreased activity (tiredness)
|
19 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Days 1-29 after vaccinationPopulation: The Safety Population includes all subjects who received at least one dose of investigational product and experienced any follow-up for safety. Treatment group was assigned based on the actual investigational product received.
SAEs were those that resulted in death; were life-threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly/birth defect in the offspring of a study participant; or were an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed above. An NOCD was a newly diagnosed medical condition of a chronic, ongoing nature and assessed by the investigator as medically significant.
Outcome measures
| Measure |
Monovalent Influenza Virus Vaccine
n=240 Participants
Frozen monovalent vaccine containing the new strain was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10\^7 fluorescent focus units (FFU) of influenza virus type B/Brisbane/60/2008 (Victoria lineage). A single dose of investigational product was administered on Day 1.
|
Placebo
n=60 Participants
Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer and egg allantoic fluid. A single dose of investigational product was administered on Day 1.
|
|---|---|---|
|
Number of Participants Reporting at Least One Serious Adverse Event (SAE) or New Onset Chronic Disease (NOCD)
Total participants reporting ≥ one SAE
|
0 participants
|
0 participants
|
|
Number of Participants Reporting at Least One Serious Adverse Event (SAE) or New Onset Chronic Disease (NOCD)
Total participants reporting ≥ one NOCD
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Days 1-181 after vaccinationPopulation: The Safety Population includes all subjects who received at least one dose of investigational product and experienced any follow-up for safety. Treatment group was assigned based on the actual investigational product received.
SAEs were those that resulted in death; were life-threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly/birth defect in the offspring of a study participant; or were an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed above. An NOCD was a newly diagnosed medical condition of a chronic, ongoing nature and assessed by the investigator as medically significant.
Outcome measures
| Measure |
Monovalent Influenza Virus Vaccine
n=240 Participants
Frozen monovalent vaccine containing the new strain was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10\^7 fluorescent focus units (FFU) of influenza virus type B/Brisbane/60/2008 (Victoria lineage). A single dose of investigational product was administered on Day 1.
|
Placebo
n=60 Participants
Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer and egg allantoic fluid. A single dose of investigational product was administered on Day 1.
|
|---|---|---|
|
Number of Participants Reporting at Least One Serious Adverse Event (SAE) or New Onset Chronic Disease (NOCD)
Total participants reporting ≥ one SAE
|
2 participants
|
0 participants
|
|
Number of Participants Reporting at Least One Serious Adverse Event (SAE) or New Onset Chronic Disease (NOCD)
Total participants reporting ≥ one NOCD
|
0 participants
|
0 participants
|
Adverse Events
Monovalent Influenza Virus Vaccine
Serious events: 2 serious events
Other events: 23 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Monovalent Influenza Virus Vaccine
n=240 participants at risk
Frozen monovalent vaccine containing the new strain was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10\^7 fluorescent focus units (FFU) of influenza virus type B/Brisbane/60/2008 (Victoria lineage). A single dose of investigational product was administered on Day 1.
|
Placebo
n=60 participants at risk
Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer and egg allantoic fluid. A single dose of investigational product was administered on Day 1.
|
|---|---|---|
|
Endocrine disorders
Thyroid disorder
|
0.42%
1/240 • Number of events 1 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
0.00%
0/60 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
|
Hepatobiliary disorders
Gallbladder disorder
|
0.42%
1/240 • Number of events 1 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
0.00%
0/60 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
|
Infections and infestations
Clostridium difficile colitis
|
0.42%
1/240 • Number of events 1 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
0.00%
0/60 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
Other adverse events
| Measure |
Monovalent Influenza Virus Vaccine
n=240 participants at risk
Frozen monovalent vaccine containing the new strain was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer, egg allantoic fluid, and approximately 10\^7 fluorescent focus units (FFU) of influenza virus type B/Brisbane/60/2008 (Victoria lineage). A single dose of investigational product was administered on Day 1.
|
Placebo
n=60 participants at risk
Placebo was supplied in intranasal sprayers containing a total volume of 0.5 mL of sucrose-phosphate buffer and egg allantoic fluid. A single dose of investigational product was administered on Day 1.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.83%
2/240 • Number of events 2 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
1.7%
1/60 • Number of events 1 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/240 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
1.7%
1/60 • Number of events 1 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
|
Reproductive system and breast disorders
Menstruation irregular
|
0.00%
0/240 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
1.7%
1/60 • Number of events 1 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.1%
17/240 • Number of events 17 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
0.00%
0/60 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
1.7%
4/240 • Number of events 4 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
0.00%
0/60 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
0.00%
0/240 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
1.7%
1/60 • Number of events 1 • From the time that written informed consent was obtained, AEs were collected through Day 15 after vaccination and SAEs were collected through Day 181 after vaccination.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER