Trial Outcomes & Findings for Evaluating the Infectivity, Safety, and Immunogenicity of a Single Dose of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (D46/NS2/N/ΔM2-2-HindIII) in RSV-Seronegative Infants 6 to 24 Months of Age (NCT NCT03102034)
NCT ID: NCT03102034
Last Updated: 2022-02-08
Results Overview
A Serious Adverse Event (SAE) was an AE, whether considered related to the study product or not, that: * Resulted in death during the period of protocol-defined surveillance * Was life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it did not refer to an event that hypothetically might have caused death were it more severe * Required inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting * Resulted in a persistent or significant disability/incapacity * Was a congenital anomaly or birth defect * Was an important medical event that might not be immediately life threatening or result in death or hospitalization but might jeopardize the patient or might require intervention to prevent one of the outcomes listed above.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
Measured from Day 0 through Day 56
Results posted on
2022-02-08
Participant Flow
Recruitment period was from April to October 2017. Participants were recruited from medical clinics.
Participant milestones
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Overall Study
STARTED
|
21
|
11
|
|
Overall Study
COMPLETED
|
20
|
11
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Evaluating the Infectivity, Safety, and Immunogenicity of a Single Dose of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (D46/NS2/N/ΔM2-2-HindIII) in RSV-Seronegative Infants 6 to 24 Months of Age
Baseline characteristics by cohort
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=21 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=11 Participants
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
9 months
n=5 Participants
|
9 months
n=7 Participants
|
9 months
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
12 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
14 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
21 participants
n=5 Participants
|
11 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Serum RSV-neutralizing antibody titers
|
2.3 log 2 titers
n=5 Participants
|
2.3 log 2 titers
n=7 Participants
|
2.3 log 2 titers
n=5 Participants
|
PRIMARY outcome
Timeframe: Measured from Day 0 through Day 28Population: Study participants who received inoculation were included.
Solicited adverse events included fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI). The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that was in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 3 and Table 4 in the protocol document.
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=21 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=11 Participants
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Fever · Did not have this AE
|
17 Participants
|
9 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Fever · Grade 1
|
3 Participants
|
1 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Fever · Grade 2
|
1 Participants
|
1 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Fever · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Fever · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Otitis Media · Did not have this AE
|
21 Participants
|
11 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Otitis Media · Grade 1
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Otitis Media · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Otitis Media · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Otitis Media · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Upper Respiratory Illness (URI) · Did not have this AE
|
6 Participants
|
10 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Upper Respiratory Illness (URI) · Grade 1
|
15 Participants
|
1 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Upper Respiratory Illness (URI) · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Upper Respiratory Illness (URI) · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Upper Respiratory Illness (URI) · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Lower Respiratory Illness (LRI) · Did not have this AE
|
21 Participants
|
11 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Lower Respiratory Illness (LRI) · Grade 1
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Lower Respiratory Illness (LRI) · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Lower Respiratory Illness (LRI) · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Lower Respiratory Illness (LRI) · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Cough, without LRI · Did not have this AE
|
9 Participants
|
11 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Cough, without LRI · Grade 1
|
12 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Cough, without LRI · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Cough, without LRI · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (AEs) by Grade
Cough, without LRI · Grade 4
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Measured from Day 0 through Day 28Population: Study participants who received inoculation were included.
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each unsolicited AE category, and that was in the line corresponding to the highest grade adverse event they had in that category. AE grading (Grade 1- mild to Grade 4-life-threatening) was done by DAIDS AE Grading table v2.0 (see References).
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=21 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=11 Participants
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Number of Participants With Unsolicited AEs by Grade
Epistaxis · Grade 1
|
1 Participants
|
1 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Epistaxis · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Epistaxis · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Epistaxis · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Nasal congestion · Did not have this AE
|
20 Participants
|
11 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Nasal congestion · Grade 1
|
1 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Nasal congestion · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Nasal congestion · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Nasal congestion · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Sneezing · Did not have this AE
|
20 Participants
|
11 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Sneezing · Grade 1
|
1 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Sneezing · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Sneezing · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Sneezing · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Eczema, Diaper rash · Did not have this AE
|
19 Participants
|
11 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Eczema, Diaper rash · Grade 1
|
2 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Eczema, Diaper rash · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Eczema, Diaper rash · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Eczema, Diaper rash · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Middle ear effusion · Did not have this AE
|
20 Participants
|
11 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Middle ear effusion · Grade 1
|
1 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Middle ear effusion · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Middle ear effusion · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Middle ear effusion · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Irritability · Did not have this AE
|
20 Participants
|
11 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Irritability · Grade 1
|
1 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Irritability · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Irritability · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Irritability · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Lymphadenopathy · Did not have this AE
|
20 Participants
|
11 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Lymphadenopathy · Grade 1
|
1 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Lymphadenopathy · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Lymphadenopathy · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Lymphadenopathy · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Diarrhea, vomiting · Did not have this AE
|
17 Participants
|
11 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Diarrhea, vomiting · Grade 1
|
4 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Diarrhea, vomiting · Grade 2
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Diarrhea, vomiting · Grade 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Diarrhea, vomiting · Grade 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Unsolicited AEs by Grade
Epistaxis · Did not have this AE
|
20 Participants
|
10 Participants
|
PRIMARY outcome
Timeframe: Measured from Day 0 through Day 56Population: Study participants who received inoculation were included.
A Serious Adverse Event (SAE) was an AE, whether considered related to the study product or not, that: * Resulted in death during the period of protocol-defined surveillance * Was life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it did not refer to an event that hypothetically might have caused death were it more severe * Required inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting * Resulted in a persistent or significant disability/incapacity * Was a congenital anomaly or birth defect * Was an important medical event that might not be immediately life threatening or result in death or hospitalization but might jeopardize the patient or might require intervention to prevent one of the outcomes listed above.
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=21 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=11 Participants
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Number of Participants With Serious Adverse Events (SAEs)
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28 for nasal washes, and at Days 0, 56 for serum RSV-neutralizing antibodiesPopulation: Study participants who received inoculation were included.
Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes) and/or 2) greater than or equal to 4-fold rise in RSV-neutralizing antibody titer from Study Day 0 and 56.
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=21 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=11 Participants
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Number of Participants Infected With RSV Vaccine Virus
|
21 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28Population: Only participants who met the definition of infection with vaccine virus were included.
This is the highest value per participant of the titer of vaccine virus shed. It was measured by culture. Only participants who met the definition of infection with vaccine virus were included.
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=21 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Peak Titer of Vaccine Virus Shed
|
3.5 log10 PFU/mL
Interval 2.9 to 3.8
|
—
|
PRIMARY outcome
Timeframe: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28. Last day positive is reported.Population: Only participants who met the definition of infection with vaccine virus were included.
Determined separately by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=21 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Duration of Vaccine Virus Shedding in Nasal Washes
Culture positive
|
10 days
Interval 7.0 to 12.0
|
—
|
|
Duration of Vaccine Virus Shedding in Nasal Washes
RT-PCR positive
|
14 days
Interval 12.0 to 17.0
|
—
|
PRIMARY outcome
Timeframe: Measured at Day 0 and Day 56Population: Study participants who received inoculation were included.
Immunogenicity was assessed pre-inoculation, and at approximately 2 months post-inoculation (Study Day 56). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=21 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=11 Participants
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titer
|
20 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Measured at Day 56Population: Study participants who received inoculation were included.
Immunogenicity was assessed at approximately 2 months post-inoculation (Study Day 56).
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=21 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=11 Participants
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Serum Antibody Responses to RSV F Glycoprotein as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
|
15.7 log 2 titers
Interval 13.9 to 15.7
|
8.1 log 2 titers
Interval 6.0 to 9.1
|
SECONDARY outcome
Timeframe: Measured from November 1st through participant's post-RSV season surveillance visitPopulation: Only participants who had RSV detected in nasal washes or greater than or equal to 4 fold rise in serum antibodies during the subsequent RSV season were included.
The number of participants who had RSV-associated, medically attended, acute respiratory illness (RSV-MAARI) or RSV-associated, medically attended, acute lower respiratory illness (RSV-MAALRI) among those who had RSV detected in nasal washes or greater than or equal to 4 fold rise in serum antibodies during the subsequent RSV season were presented.
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=6 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=4 Participants
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season
RSV-MAARI
|
2 Participants
|
3 Participants
|
|
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season
RSV-MAALRI
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Measured through participant's last study visit, up to a total of 6 to 13 months depending on when participants enrolled in the studyPopulation: Only participants who had RSV detected in nasal washes or a greater than or equal to 4-fold rise in serum antibodies during the subsequent RSV season were included.
Only participants who had RSV detected in nasal washes or a greater than or equal to 4-fold rise in serum antibodies during the subsequent RSV season were included. RSV-neutralizing antibody titers were measured pre- and post-RSV surveillance season.
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=6 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=4 Participants
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Magnitude of Serum RSV-neutralizing Antibody Responses in the Vaccine and Placebo Recipients Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season.
Pre-RSV surveillance
|
6.3 log 2 titers
Interval 4.5 to 7.7
|
2.3 log 2 titers
Interval 2.3 to 2.8
|
|
Magnitude of Serum RSV-neutralizing Antibody Responses in the Vaccine and Placebo Recipients Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season.
Post-RSV Surveillance
|
10.4 log 2 titers
Interval 6.4 to 11.0
|
7.1 log 2 titers
Interval 5.9 to 8.8
|
SECONDARY outcome
Timeframe: Measured at day 0 and Day 56Population: All participants who received inoculation were included.
A B cell response to vaccine is indicated by a greater than or equal to 4-fold change in serum antibody titers to RSV F glycoprotein between the pre- and post-inoculation time points.
Outcome measures
| Measure |
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
n=21 Participants
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=11 Participants
Participants received a single dose of placebo at study entry (Day 0).
Placebo: Isotonic diluent; administered as nose drops
|
|---|---|---|
|
Number of Participants With B Cell Responses to Vaccine
|
21 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Measured at Day 0, 28 and 56Determined from nasal wash samples. This outcome has been changed from a secondary outcome measure to an 'other pre-specified' outcome measure. Since this outcome measure relies on previously untested assays to reliably quantify RSV specific mucosal antibodies from nasal wash samples, it was changed to other pre-specified to fit with its intended analysis type.
Outcome measures
Outcome data not reported
Adverse Events
Vaccine
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Vaccine
n=21 participants at risk
Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
D46/NS2/N/ΔM2-2-HindIII: 10\^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
|
Placebo
n=11 participants at risk
Participants received a single dose of placebo study entry (Day 0). Placebo: Isotonic diluent, administered as nose drops
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
4.8%
1/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
9.1%
1/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Gastrointestinal disorders
Diarrhoea
|
23.8%
5/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
0.00%
0/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Gastrointestinal disorders
Infantile vomiting
|
9.5%
2/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
0.00%
0/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
General disorders
Pyrexia
|
47.6%
10/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
54.5%
6/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Infections and infestations
Conjunctivitis viral
|
0.00%
0/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
9.1%
1/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Infections and infestations
Otitis media acute
|
23.8%
5/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
18.2%
2/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Infections and infestations
Respiratory syncytial virus bronchiolitis
|
0.00%
0/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
9.1%
1/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Infections and infestations
Upper respiratory tract infection
|
23.8%
5/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
18.2%
2/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
19.0%
4/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
18.2%
2/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
66.7%
14/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
36.4%
4/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.8%
1/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
9.1%
1/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
19.0%
4/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
27.3%
3/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
76.2%
16/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
36.4%
4/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
4.8%
1/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
9.1%
1/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/21 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
9.1%
1/11 • From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.
From day 0-28, all SAEs, solicited AEs, and unsolicited AEs, with the exception of the following if not treated with prescription medication or over the counter medications with antipyretic properties: diaper rashes, teething pain, and spitting up. SAEs and LRIs were reported according to DAIDS EAE Manual V2.0 (see References). From day 29-56, SAEs were collected. After day 56, from November 1 - March 31 of the following year, medically attended fever, LRI, URI and otitis media were collected.
|
Additional Information
Melissa Allen, Director, IMPAACT Operations Center
Family Health International (FHI 360)
Phone: (919) 405-1429
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place