Open-Label Study of H5 Vaccine in Participants of Protocol 04-077

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00402649
• Collaborator: (none)
• Enrollment: 35
• Locations: 3
• Arm: 1
• Duration (Months): 10
• Patients Per Site: 11.7
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This study may provide safety information on a flu vaccine given to children and may provide immunogenicity information to add to what was collected in a previous flu vaccine study. Participants will include 55 healthy children, ages 2-10, who participated in 04-077 and received a placebo injection instead of the flu vaccine or were incompletely immunized. The study has 2 purposes: to make sure there are no serious side effects in children and to see how the immune systems react to the vaccine. Study procedures include up to 4 study visits, up to 9 follow-up phone calls, 2 blood samples to be collected during visits 1 and 3, and up to 3 vaccine injections in the arm or thigh muscle. Parents will be given a memory aid card to record side effects, temperatures, and medications. Parents will have the option for the child to receive a 3rd dose of vaccine if offered, at month 6. This booster shot will require a 6-month visit and participation for an additional 6 months.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: Inactivated Influenza A/H5N1 Vaccine (sanofi pasteur)	Phase 1/Phase 2

Detailed Description

The recent emergence of novel influenza virus strains in human populations has encouraged efforts to develop vaccines for a potential pandemic. The objectives of this study are to evaluate the safety of intramuscular (IM) subvirion inactivated H5N1 vaccine in healthy children aged 2 through 10 years and to determine the immunogenicity profile of IM subvirion inactivated H5N1 vaccine in healthy children approximately 1 month following receipt of the second of 2 doses of vaccine. Study endpoints include: adverse event (AE) and serious adverse event (SAE) information (solicited in-clinic and via memory aids, concomitant medications, and periodic targeted physical assessments, as indicated); proportion of subjects achieving a serum hemagglutination inhibition antibody titer of 1:40 against the influenza A/H5N1 virus 28 days after receipt of second dose of vaccine (approximately Day 56); geometric mean titer and the frequency of 4-fold or greater increases in hemagglutination inhibition antibody titers 28 days after receipt of second dose of vaccine (approximately Day 56); and development of serum antibody responses against antigenically drifted variants of influenza H5N1 virus. This study is linked to DMID protocol 06-0072. Up to 55 healthy children, aged 2 through 10 years, who previously participated in DMID 04-077, will be eligible for enrollment in this multimember, open-label, phase I/II clinical trial to receive at least 2 and up to 3 doses of an inactivated influenza A/H5N1 vaccine at a 45-micrograms dose. The vaccine dosage level that will be used in this study was chosen based upon safety and immunogenicity data collected previously in adults and children. The injection volume of the 90-micrograms dose is 1 mL for the vaccine being used in this study, but this is considered unacceptable in this age group. Therefore, the 45-micrograms dose (0.5 ml volume) has been selected. Twenty three subjects who were previously enrolled and assigned to placebo in the DMID 04-077 study (A Randomized, Double-Blinded, Placebo-Controlled, Phase I/II, Study of the Safety, Reactogenicity, and Immunogenicity of Intramuscular Inactivated Influenza A/H5N1 Vaccine in Healthy Children Aged 2 Years Through 9 Years) along with up to 32 subjects from a single site who were incompletely immunized are eligible for enrollment in this study. Vaccine will be administered into the deltoid or (if age appropriate) thigh muscle. All subjects will receive 2 doses of the vaccine approximately 28 days apart. At month 6, subjects' parent(s) or guardian(s) will be called to assess the subjects for serious adverse events. Blood collection for immunogenicity studies will be at the discretion of the parent(s) or legal guardian(s). Should data evaluating a third dose of the influenza A/H5N1 vaccine show enhanced immunogenicity in pediatric subjects participating in DMID 04-077, parents/guardians of subjects who received vaccine will be offered the possibility of a third dose for their participating children.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Open-Label Study of Intramuscular Inactivated Influenza A/H5N1 Vaccine in Healthy Children Aged 2 Years to 10 Years
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Oct 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.	Biological: Inactivated Influenza A/H5N1 Vaccine (sanofi pasteur); Inactivated influenza A/H5N1 vaccine administered via intramuscular (IM) injection; dosage 45-mcg.

Outcome Measures

Primary Outcome Measures

1. Occurrence of Solicited Adverse Events Among All Subjects [Days 0-7 post each vaccination]

   Number of subjects reporting solicited Adverse Events collected on Memory Aid for Days 0-7 post each vaccination for all subjects (systematic assessment), for any and severe severities.

2. Occurrence of the Solicited Adverse Event of Body Aches, Solicited Only From Children Age 6-10 [Days 0-7 post each vaccination]

   Number of subjects reporting solicited Adverse Event of Body Aches, collected on Memory Aid for Days 0-7 post each vaccination for children age 6-10 only (systematic assessment), of any and severe severities.

3. Occurrence of Unsolicited Adverse Events [Through Day 28 after second vaccination]

   Number of subjects with spontaneous reports of Adverse Events of any and severe severities. Events reported by more than 5.6% of subjects in any group are reported by MedDRA Preferred Term.

4. Occurrence of Serious Adverse Events [6 months after the first vaccination]

   Number of subjects with Serious Adverse Events during the 6 months after the first vaccination.

Secondary Outcome Measures

1. Number of Participants With Serum Hemagglutination Inhibition (HAI) Antibody Titers of 1:40 or Greater [Day 28 after second vaccination]

   Number of subjects achieving serum hemagglutination inhibition antibody titer of 1:40 or greater against the influenza A/H5N1 virus after receipt of two doses of vaccine.

2. Geometric Mean Titer of Hemagglutination Inhibition Antibody Titers [Day 28 after second vaccination]

   Geometric mean titer of hemagglutination inhibition antibody titers after receipt of two doses of vaccine.

3. Number of Participants With a Four-fold or Greater Increase in Hemagglutination Inhibition Antibody Titers [Day 28 after second vaccination]

   Number of subjects with a 4-fold or greater increase, relative to baseline, in hemagglutination inhibition antibody titers after receipt of two doses of vaccine.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 10 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• The subject must be male or female, aged 2 through 10 years at enrollment, and must have participated in protocol 04-077 as a placebo recipient or a subject at the UCLA site.

• The subject must be in good health (and not on any chronic medications), as determined by medical history and a history-directed targeted physical examination.

• Parents or guardians of the subject must be able to understand and comply with planned study procedures and be available for all study visits.

• Parents or guardians of the subject must provide written consent prior to initiation of any study procedures, and subject may provide written assent as appropriate.

Exclusion Criteria:

• The subject must not have a known allergy to eggs or other components of the vaccine or sensitivity or allergy to latex.

• The subject must not have a history of asthma or recurrent wheezing.

• The subject must not be undergoing immunosuppression as a result of an underlying illness or treatment.

• The subject must not have an active neoplastic disease or a history of any hematologic malignancy.

• The subject must not be using oral or parenteral steroids, inhaled steroids, or other immunosuppressive or cytotoxic drugs. Note: Subjects on nasal or topical steroids will be allowed to enroll in this study.

• The subject must not have a history of receiving immunoglobulin or other blood product within the 3 months prior to enrollment in this study.

• The subject must not receive any other inactivated vaccines within 2 weeks before or after any study vaccine or any other live vaccines within 4 weeks before or after any study vaccine in this study.

• The subject must not have an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses (these conditions include, but are not limited to, known chronic liver disease, significant renal disease, unstable or progressive neurological disorders, diabetes mellitus, and transplant recipients).

• The subject must not have a history of severe reactions following immunization with contemporary influenza virus vaccines.

• The subject must not have an acute illness, including an axillary temperature greater than or equal to 100 degrees F or an oral temperature greater than or equal to 101 degrees F within 3 days prior to vaccination.

• The subject must not have received an experimental vaccine or medication within 1 month prior to enrollment in this study, or expect to receive an experimental vaccine, medication, or blood product during the 13-month study period.

• The subject must not have any condition that would, in the opinion of the investigator, place them at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

• The subject must not have a history of Guillain-Barré syndrome.

• The subject must not be participating concurrently in another clinical trial aside from DMID 04-077 (either in active phase or in follow-up phase).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Center For Vaccine Research	Torrance	California	United States	90502
2	University of Maryland Baltimore	Baltimore	Maryland	United States	21201
3	Saint Louis University	St. Louis	Missouri	United States	63104

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00402649
• Other Study ID Numbers: 06-0072
• First Posted: Nov 22, 2006
• Last Update Posted: Jun 13, 2011
• Last Verified: May 1, 2008

• Keywords provided by , ,: influenza, A/H5N1, avian influenza, vaccine
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	Recruitment was offered to the 23 subjects (aged 2-10 years) who were previously enrolled and assigned to placebo at the three clinical sites in the DMID 04-077 study (NCT00133536), along with up to 32 subjects from a single site who were incorrectly dosed in that study.

Arm/Group Title	Inactivated Influenza A/H5N1 Vaccine
Arm/Group Description	All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.
Period Title: Overall Study
STARTED	35
COMPLETED	33
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Inactivated Influenza A/H5N1 Vaccine
Arm/Group Description	All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.
Overall Participants	35
Age (Count of Participants)
<=18 years	35 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.6 (2.3)
Sex: Female, Male (Count of Participants)
Female	16 45.7%
Male	19 54.3%
Region of Enrollment (participants) [Number]
United States	35 100%

Outcome Measures

1. Primary Outcome

Title	Occurrence of Solicited Adverse Events Among All Subjects
Description	Number of subjects reporting solicited Adverse Events collected on Memory Aid for Days 0-7 post each vaccination for all subjects (systematic assessment), for any and severe severities.
Time Frame	Days 0-7 post each vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inactivated Influenza A/H5N1 Vaccine
Arm/Group Description	All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.
Measure Participants	35
Elevated Oral Temperature of any severity	0 0%
Elevated Oral Temperature - severe	0 0%
General Activity of any severity	10 28.6%
General Activity - severe	1 2.9%
Pain of any severity	19 54.3%
Pain - severe	0 0%
Mobility of any severity	5 14.3%
Mobility - severe	0 0%
Redness of any severity	4 11.4%
Redness - severe	0 0%
Swelling of any severity	4 11.4%
Swelling - severe	0 0%
Rash of any severity	0 0%
Rash - severe	0 0%

2. Secondary Outcome

Title	Number of Participants With Serum Hemagglutination Inhibition (HAI) Antibody Titers of 1:40 or Greater
Description	Number of subjects achieving serum hemagglutination inhibition antibody titer of 1:40 or greater against the influenza A/H5N1 virus after receipt of two doses of vaccine.
Time Frame	Day 28 after second vaccination

Outcome Measure Data

Analysis Population Description

Blood draw was optional - blood collected from 16 participants

Arm/Group Title	Inactivated Influenza A/H5N1 Vaccine
Arm/Group Description	All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.
Measure Participants	16
Number [Participants]	7 20%

3. Secondary Outcome

Title	Geometric Mean Titer of Hemagglutination Inhibition Antibody Titers
Description	Geometric mean titer of hemagglutination inhibition antibody titers after receipt of two doses of vaccine.
Time Frame	Day 28 after second vaccination

Outcome Measure Data

Analysis Population Description

Blood draw was optional - blood collected from 16 participants

Arm/Group Title	Inactivated Influenza A/H5N1 Vaccine
Arm/Group Description	All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.
Measure Participants	16
Geometric Mean (95% Confidence Interval) [Titer]	20.9

4. Secondary Outcome

Title	Number of Participants With a Four-fold or Greater Increase in Hemagglutination Inhibition Antibody Titers
Description	Number of subjects with a 4-fold or greater increase, relative to baseline, in hemagglutination inhibition antibody titers after receipt of two doses of vaccine.
Time Frame	Day 28 after second vaccination

Outcome Measure Data

Analysis Population Description

Blood draw was optional - blood collected from 16 participants post vaccination, but missing baseline assessment for 3 of 16 subjects

Arm/Group Title	Inactivated Influenza A/H5N1 Vaccine
Arm/Group Description	All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.
Measure Participants	13
Number [Participants]	4 11.4%

5. Primary Outcome

Title	Occurrence of the Solicited Adverse Event of Body Aches, Solicited Only From Children Age 6-10
Description	Number of subjects reporting solicited Adverse Event of Body Aches, collected on Memory Aid for Days 0-7 post each vaccination for children age 6-10 only (systematic assessment), of any and severe severities.
Time Frame	Days 0-7 post each vaccination

Outcome Measure Data

Analysis Population Description

Solicited symptom of Body Aches was collected from subjects age 6-10 only

Arm/Group Title	Inactivated Influenza A/H5N1 Vaccine
Arm/Group Description	All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.
Measure Participants	26
Body Aches of any severity	6 17.1%
Body Aches - severe	0 0%

6. Primary Outcome

Title	Occurrence of Unsolicited Adverse Events
Description	Number of subjects with spontaneous reports of Adverse Events of any and severe severities. Events reported by more than 5.6% of subjects in any group are reported by MedDRA Preferred Term.
Time Frame	Through Day 28 after second vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inactivated Influenza A/H5N1 Vaccine
Arm/Group Description	All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.
Measure Participants	35
Vomiting of any severity	2 5.7%
Vomiting - severe	0 0%
Gastrointestinal viral of any severity	2 5.7%
Gastrointestinal viral - severe	0 0%
Nasopharyngitis of any severity	2 5.7%
Nasopharyngitis - severe	0 0%
Upper respiratory tract infection of any severity	2 5.7%
Upper respiratory tract infection - severe	0 0%
Headache of any severity	2 5.7%
Headache - severe	0 0%
Rhinitis allergic of any severity	2 5.7%
Rhinitis allergic - severe	0 0%

7. Primary Outcome

Title	Occurrence of Serious Adverse Events
Description	Number of subjects with Serious Adverse Events during the 6 months after the first vaccination.
Time Frame	6 months after the first vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inactivated Influenza A/H5N1 Vaccine
Arm/Group Description	All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.
Measure Participants	35
Number [Participants]	0 0%

Adverse Events

Time Frame	Subjects' parents/guardians recorded solicited symptoms on a memory aid for 8 days (Day 0-7) following each dose. Unsolicited non-serious adverse events were collected for 28 days after each dose and serious adverse events were collected through Day 180.
Adverse Event Reporting Description	The solicited symptoms are reported separately after each vaccination. The occurrence of a solicited symptom on any day(s) at any severity within the 8 day period was considered one event.
Arm/Group Title	Inactivated Influenza A/H5N1 Vaccine
Arm/Group Description	All subjects will receive at least 2 and up to 3 doses of the vaccine approximately 28 days apart.
All Cause Mortality
	Inactivated Influenza A/H5N1 Vaccine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Inactivated Influenza A/H5N1 Vaccine
	Affected / at Risk (%)	# Events
Total	0/35 (0%)
Other (Not Including Serious) Adverse Events
	Inactivated Influenza A/H5N1 Vaccine
	Affected / at Risk (%)	# Events
Total	26/35 (74.3%)
Gastrointestinal disorders
Vomiting	2/35 (5.7%)	2
General disorders
Pain - post dose 1	5/35 (14.3%)	5
Pain - post dose 2	2/32 (6.3%)	2
Injection site erythema - post dose 1	4/35 (11.4%)	4
Injection site erythema - post dose 2	2/32 (6.3%)	2
Injection site swelling - post dose 1	4/35 (11.4%)	4
Injection site swelling - post dose 2	2/32 (6.3%)	2
Injection site pain - post dose 1	11/35 (31.4%)	11
Injection site pain - post dose 2	15/32 (46.9%)	15
Decreased activity - post dose 1	6/35 (17.1%)	6
Decreased activity - post dose 2	5/35 (14.3%)	5
Infections and infestations
Gastroenteritis viral	2/35 (5.7%)	2
Nasopharyngitis	2/35 (5.7%)	2
Upper respiratory tract infection	2/35 (5.7%)	2
Musculoskeletal and connective tissue disorders
Joint range of motion decreased - post dose 1	5/35 (14.3%)	5
Joint range of motion decreased - post dose 2	3/35 (8.6%)	3
Nervous system disorders
Headache	2/35 (5.7%)	3
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic	2/35 (5.7%)	2

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.