Safety and Immunogenicity of a Single Dose of Intranasal Seasonal Trivalent Live-Attenuated Influenza Vaccine

• Sponsor: PATH Vaccine Solutions (Other)
• Overall Status: Completed
• CT.gov ID: NCT01625689
• Collaborator: Johns Hopkins Bloomberg School of Public Health (Other), International Centre for Diarrhoeal Disease Research, Bangladesh (Other)
• Enrollment: 309
• Location: 1
• Arms: 2
• Duration (Months): 8
• Patients Per Site Per Month: 38.4

Study Details

Study Description

Brief Summary

In this Phase II randomized controlled clinical trial, generally healthy male and female children from 24 through 59 months of age will be enrolled in Kamalapur (Dhaka), Bangladesh. The study is expected to continue for at least 6 months following vaccination. The experimental intervention is Serum Institute of India Ltd's Trivalent, Seasonal Live Attenuated Influenza Vaccine (SIIL LAIV). The study vaccine has been formulated according to WHO recommendations for the 2011-2012 Northern Hemisphere influenza season. The SIIL LAIV is administered in a 0.5 ml intranasal dose (one spray of 0.25 ml per nostril) via a reusable sprayer device and a single-use nozzle that produces a fine mist that is primarily deposited in the nose and nasopharynx. The comparator vaccine will be an inactive placebo identical in appearance to the active vaccine.

The primary study hypothesis is that LAIV is safe and well tolerated by children aged 24 through 59 months in Bangladesh. A secondary hypothesis is that LAIV is immunogenic among children receiving study vaccine as compared to children receiving placebo.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: SIIL LAIV (live, trivalent seasonal influenza vaccine); Biological: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 309 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Assessment of the Safety and Immunogenicity of a Single Dose of Intranasal Seasonal Trivalent Live-Attenuated Influenza Vaccine Among Children Aged 24 Through 59 Months in Bangladesh
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SIIL LAIV SII LAIV is a live, trivalent seasonal influenza vaccine. The viral strains in seasonal trivalent influenza vaccine (human, live attenuated) are antigenically similar to A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 Type B, as per the WHO recommended strains for the Northern hemisphere 2011-12 influenza season	Biological: SIIL LAIV (live, trivalent seasonal influenza vaccine); Dose: 0.5 mL, The viral strains in seasonal trivalent influenza vaccine (human, live attenuated) are antigenically similar to A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 Type B, as per the WHO recommended strains for the Northern hemisphere 2011-12 influenza season
Placebo Comparator: Placebo Placebo identical in appearance to experimental vaccine.	Biological: Placebo; Inactive placebo will be identical to SII LAIV in appearance, ingredients, and concentrations, except it will be missing attenuated influenza virus.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes [6 months following vaccination]

   PDWI: Participants meeting illness criteria, seeking care in health facility, and with wheeze identified by a study physician Illness criteria: The presence of one Category A (Fever (>=38°C), tachypnea, danger signs (chest-indrawing, lethargy, cyanosis, inability to drink, convulsions), difficult breathing, noisy breathing, ear pain or discharge) or two Category B findings (Cough, rhinorrhea, sore throat, myalgia/arthralgia, chills, headache, irritability/decreased activity, vomiting) Wheeze: Long high-pitched whistling or musical sound on expiration heard by auscultation

2. Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes [42 days following vaccination]

   PDWI: Participants meeting illness criteria, seeking care in health facility, and with wheeze identified by a study physician Illness criteria: The presence of one Category A (Fever (>=38°C), tachypnea, danger signs (chest-indrawing, lethargy, cyanosis, inability to drink, convulsions), difficult breathing, noisy breathing, ear pain or discharge) or two Category B findings (Cough, rhinorrhea, sore throat, myalgia/arthralgia, chills, headache, irritability/decreased activity, vomiting) Wheeze: Long high-pitched whistling or musical sound on expiration heard by auscultation

3. Percentage of Participants With Unsolicited Adverse Events (AEs) [Throughout study period, through at least 6 months following vaccination]

4. Percentage of Participants With Solicited Local and Systemic Reactions [Through 7 days following vaccination]

   Local reactions: Nasal discomfort, Runny nose, Stuffy nose, Sneezing, Ear pain Systemic Reactions: Cough, Headache, Loss of Appetite, Fever, Irritability, Nausea, Sore throat, Lethargy

Secondary Outcome Measures

1. The Post-vaccination Anti-influenza Immunologic Response Will be Measured Based on the Type of Immunologic Assay and Categorized by Vaccine Virus Strain, Participant Baseline Serostatus, and Vaccine Allocation [Approximately 21 days post-vaccination]

2. Post Vaccination SIIL LAIV Virus Shedding/Vaccine-take Will be Parameterized by the Percentage of Participants With Detectable Virus by Post Vaccination Day. [2, 4, and 7 days post-vaccination]

3. Clinical Characteristics of Influenza, Including Influenza Coinfections With Other Bacterial and Viral Respiratory Pathogens, Will be Parameterized as the Percentage of Participants Categorized by Vaccine Allocation [6 months post-vaccination]

4. Viral Etiologies of Acute Respiratory and Febrile Illness Will be Parameterized as the Percentage of Those With Each Particular Laboratory-confirmed Respiratory Virus Infection Categorized by Vaccine Allocation [6 months post-vaccination]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 24 Months to 59 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male or female child at least 24 months of age and no older than 59 months of age at the time of study vaccination

• A child whose parent or guardian's primary residence, at the time of study vaccinations, is within the Kamalapur surveillance site catchment area and who intends to be present in the area for the duration of the trial

• A child whose parent or legal guardian is willing to provide written informed consent prior to the participant's study vaccination

Exclusion Criteria:

• Has any serious chronic disease including progressive neurologic disease, tuberculosis, Down's syndrome or other cytogenetic disorder, or known or suspected disease of the immune system

• Is receiving immunosuppressive agents including systemic corticosteroids during the two weeks prior to study vaccination

• Has a history of documented hypersensitivity to eggs or other components of the vaccine (including gelatin, sorbitol, lactalbumin and chicken protein), or with life-threatening reactions to previous influenza vaccinations

• Is receiving aspirin therapy or aspirin-containing therapy currently or two weeks before

• Lives in household with somebody currently participating in a respiratory vaccination or antiviral study

• Has current or past participation (within 2 months of trial enrollment visit) in any clinical trial involving a drug or biologic with activity against respiratory disease

• Has any condition determined by investigator as likely to interfere with evaluation of the vaccine or be a significant potential health risk to the child

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ICDDR,B Kamalapur	Dhaka		Bangladesh

Sponsors and Collaborators

• PATH Vaccine Solutions
• Johns Hopkins Bloomberg School of Public Health
• International Centre for Diarrhoeal Disease Research, Bangladesh

Investigators

• Principal Investigator: W. Abdullah Brooks, MD, MPH, JHSPH, ICDDR,B

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: PATH Vaccine Solutions
• ClinicalTrials.gov Identifier: NCT01625689
• Other Study ID Numbers: LAIV-BD-01
• First Posted: Jun 21, 2012
• Last Update Posted: Jun 1, 2015
• Last Verified: Jun 1, 2012

• Keywords provided by PATH Vaccine Solutions: Influenza vaccines; Influenza, Human; Live Attenuated Influenza Vaccine
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Pre-assignment Detail	309 participants were consented and enrolled in the study. 9 participants were ineligible to receive study vaccination. 300 total participants were vaccinated and followed through the study period.

Arm/Group Title	Serum Institute of India, Ltd. (SIIL) LAIV	Placebo
Arm/Group Description	The Serum Institute of India, Ltd. (SIIL) live attenuated influenza vaccine (LAIV) (human, live attenuated, trivalent seasonal influenza vaccine): The viral strains in are antigenically similar to A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 Type B, as per the WHO recommended strains for the Northern hemisphere 2011-12 influenza season	Inactive placebo was identical to SIIL LAIV in appearance, ingredients, and concentrations, except it was missing attenuated influenza virus.
Period Title: Overall Study
STARTED	150	150
COMPLETED	148	149
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	SIIL LAIV	Placebo	Total
Arm/Group Description	The SIIL LAIV (human, live attenuated, trivalent seasonal influenza vaccine): The viral strains in are antigenically similar to A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 Type B, as per the WHO recommended strains for the Northern hemisphere 2011-12 influenza season	Inactive placebo was identical to the SIIL LAIV in appearance, ingredients, and concentrations, except it was missing attenuated influenza virus.	Total of all reporting groups
Overall Participants	150	150	300
Age (Count of Participants)
<=18 years	150 100%	150 100%	300 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	73 48.7%	66 44%	139 46.3%
Male	77 51.3%	84 56%	161 53.7%
Region of Enrollment (participants) [Number]
Bangladesh	150 100%	150 100%	300 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes
Description	PDWI: Participants meeting illness criteria, seeking care in health facility, and with wheeze identified by a study physician Illness criteria: The presence of one Category A (Fever (>=38°C), tachypnea, danger signs (chest-indrawing, lethargy, cyanosis, inability to drink, convulsions), difficult breathing, noisy breathing, ear pain or discharge) or two Category B findings (Cough, rhinorrhea, sore throat, myalgia/arthralgia, chills, headache, irritability/decreased activity, vomiting) Wheeze: Long high-pitched whistling or musical sound on expiration heard by auscultation
Time Frame	6 months following vaccination

Outcome Measure Data

Analysis Population Description

Safety analysis population

Arm/Group Title	SIIL LAIV	Placebo
Arm/Group Description	The SIIL LAIV (human, live attenuated, trivalent seasonal influenza vaccine): The viral strains in are antigenically similar to A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 Type B, as per the WHO recommended strains for the Northern hemisphere 2011-12 influenza season	Inactive placebo was identical to SII LAIV in appearance, ingredients, and concentrations, except it was missing attenuated influenza virus.
Measure Participants	150	150
Serious Adverse Events	6 4%	0 0%
Protocol Defined Wheezing Illness (PDWI)	13 8.7%	16 10.7%
Hospitalizations	3 2%	0 0%

2. Primary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes
Description	PDWI: Participants meeting illness criteria, seeking care in health facility, and with wheeze identified by a study physician Illness criteria: The presence of one Category A (Fever (>=38°C), tachypnea, danger signs (chest-indrawing, lethargy, cyanosis, inability to drink, convulsions), difficult breathing, noisy breathing, ear pain or discharge) or two Category B findings (Cough, rhinorrhea, sore throat, myalgia/arthralgia, chills, headache, irritability/decreased activity, vomiting) Wheeze: Long high-pitched whistling or musical sound on expiration heard by auscultation
Time Frame	42 days following vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Primary Outcome

Title	Percentage of Participants With Unsolicited Adverse Events (AEs)
Time Frame	Throughout study period, through at least 6 months following vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SIIL LAIV	Placebo
Arm/Group Description	The SIIL LAIV (human, live attenuated, trivalent seasonal influenza vaccine): The viral strains in are antigenically similar to A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 Type B, as per the WHO recommended strains for the Northern hemisphere 2011-12 influenza season	Inactive placebo was identical to SII LAIV in appearance, ingredients, and concentrations, except it was missing attenuated influenza virus.
Measure Participants	150	150
Diarrheal Illness	25.3 16.9%	21.3 14.2%
Oral thrush	17.3 11.5%	12.0 8%
Boil/abscess/skin infection/ulcer/cyst	7.3 4.9%	12.0 8%
Helminthiasis	6.0 4%	7.3 4.9%
Scabies	5.3 3.5%	4.0 2.7%
Abdominal pain/distension	3.3 2.2%	4.0 2.7%
Allergy	4.0 2.7%	4.0 2.7%
Fungal Infection	4.0 2.7%	3.3 2.2%
Other	36.7 24.5%	34.0 22.7%

4. Primary Outcome

Title	Percentage of Participants With Solicited Local and Systemic Reactions
Description	Local reactions: Nasal discomfort, Runny nose, Stuffy nose, Sneezing, Ear pain Systemic Reactions: Cough, Headache, Loss of Appetite, Fever, Irritability, Nausea, Sore throat, Lethargy
Time Frame	Through 7 days following vaccination

Outcome Measure Data

Analysis Population Description

Safety analysis population

Arm/Group Title	SIIL LAIV	Placebo
Arm/Group Description	The SIIL LAIV (human, live attenuated, trivalent seasonal influenza vaccine): The viral strains in are antigenically similar to A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 Type B, as per the WHO recommended strains for the Northern hemisphere 2011-12 influenza season	Inactive placebo was identical to SII LAIV in appearance, ingredients, and concentrations, except it was missing attenuated influenza virus.
Measure Participants	150	150
Measured fever (>=38.0)	3.3 2.2%	3.3 2.2%
Ear pain	1.3 0.9%	1.3 0.9%
Cough	6.7 4.5%	5.3 3.5%
Runny nose/nasal congestion	20.7 13.8%	22.7 15.1%
Sore throat	1.3 0.9%	0.0 0%
Headache	0.7 0.5%	0.0 0%
Irritability/decreased activitity	0.0 0%	0.0 0%
Vomiting	1.3 0.9%	2.0 1.3%
Lethargy	0.0 0%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SIIL LAIV, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>=0.498
	Comments	No comparison between the LAIV and placebo groups by type of solicited reaction had a p-value below 0.498.
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	The Post-vaccination Anti-influenza Immunologic Response Will be Measured Based on the Type of Immunologic Assay and Categorized by Vaccine Virus Strain, Participant Baseline Serostatus, and Vaccine Allocation
Time Frame	Approximately 21 days post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Post Vaccination SIIL LAIV Virus Shedding/Vaccine-take Will be Parameterized by the Percentage of Participants With Detectable Virus by Post Vaccination Day.
Time Frame	2, 4, and 7 days post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Clinical Characteristics of Influenza, Including Influenza Coinfections With Other Bacterial and Viral Respiratory Pathogens, Will be Parameterized as the Percentage of Participants Categorized by Vaccine Allocation
Time Frame	6 months post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Viral Etiologies of Acute Respiratory and Febrile Illness Will be Parameterized as the Percentage of Those With Each Particular Laboratory-confirmed Respiratory Virus Infection Categorized by Vaccine Allocation
Time Frame	6 months post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Throughout study period, through at least 6 months post-vaccination.
Arm/Group Title	SIIL LAIV		Placebo
Arm/Group Description	The SIIL LAIV (human, live attenuated, trivalent seasonal influenza vaccine): The viral strains in are antigenically similar to A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 Type B, as per the WHO recommended strains for the Northern hemisphere 2011-12 influenza season		Inactive placebo was identical to SII LAIV in appearance, ingredients, and concentrations, except it was missing attenuated influenza virus.
All Cause Mortality
	SIIL LAIV		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	SIIL LAIV		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/150 (4%)		0/150 (0%)
Gastrointestinal disorders
abdominal pain/gastroenteritis	2/150 (1.3%)	2	0/150 (0%)	0
Injury, poisoning and procedural complications
Traumatic Injury/fracture/overdose	4/150 (2.7%)	4	0/150 (0%)	0
Other (Not Including Serious) Adverse Events
	SIIL LAIV		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/150 (64%)		94/150 (62.7%)
Gastrointestinal disorders
diarrheal illness	38/150 (25.3%)		32/150 (21.3%)
Abdominal pain/distension	5/150 (3.3%)		6/150 (4%)
General disorders
Allergy	6/150 (4%)		6/150 (4%)
Infections and infestations
Oral thrush	26/150 (17.3%)		18/150 (12%)
Boil/Abscess/skin infection/ulcer/cyst	11/150 (7.3%)		18/150 (12%)
Helminthiasis	9/150 (6%)		7/150 (4.7%)
Scabies	8/150 (5.3%)		6/150 (4%)
Fungal Infection	6/150 (4%)		5/150 (3.3%)
Other	55/150 (36.7%)		51/150 (34%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.