Study of Inactivated, Split-Virion Influenza Vaccine Compared With Standard Fluzone Vaccine in Elderly Subjects

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00388583
• Collaborator: (none)
• Enrollment: 817
• Locations: 17
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 48.1
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

As a result of the safety and immunogenicity data generated from earlier dose-ranging studies, the present formulation has been selected for further development in the elderly.

Primary Objective:

To compare the immunogenicity in subjects receiving investigational Fluzone with those of subjects receiving standard Fluzone®.

Secondary Objectives:

Immunogenicity:

To describe the immunogenicity in subjects receiving investigational Fluzone and standard Fluzone®.

Safety:

To evaluate and describe the safety profile of investigational Fluzone in terms of solicited- and unsolicited adverse events and serious adverse events post-vaccination.

Condition or Disease	Intervention/Treatment	Phase
Orthomyxoviridae Infection; Influenza; Myxovirus Infection	Biological: Split, Inactivated, Trivalent Influenza Vaccine; Biological: Split, Inactivated, Trivalent Influenza Vaccine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 817 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of The Split, Inactivated, Trivalent Influenza Vaccine Administered by Intradermal Route in Comparison With Intramuscular Vaccination With Standard Fluzone® in Ambulatory Elderly Subjects
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Jun 1, 2007
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluzone Intradermal (ID) Vaccine Group Participants received a dose of Fluzone Intradermal (ID) Influenza Vaccine	Biological: Split, Inactivated, Trivalent Influenza Vaccine; 0.1 mL, Intradermal; Other Names: Fluzone
Active Comparator: Fluzone Intramuscular (IM) Vaccine Group Participants received a dose of Fluzone Intramuscular (IM) Influenza Vaccine.	Biological: Split, Inactivated, Trivalent Influenza Vaccine; 0.5 mL, Intramuscular; Other Names: Fluzone® 2006/2007 Formulation

Outcome Measures

Primary Outcome Measures

1. Number of Participants With at Least a 4-Fold Increase in Serum HAI Antibody Titer Post-vaccination With Either Fluzone Intradermal or Fluzone Intramuscular Vaccine. [Pre-vaccination and Day 28 post-vaccination]

   The serological determinations of total anti-influenza antibodies were performed using an Hemagglutinin inhibition (HAI) test.

2. Number of Participants Who Achieved Seroprotection Post-vaccination With Either Fluzone Intradermal or Fluzone Intramuscular Vaccine. [Day 28 post-vaccination]

   Seroprotection was defined as a post-vaccination Hemagglutinin inhibition (HAI) antibody titer ≥ 40

Secondary Outcome Measures

1. Geometric Mean Antibody Titers (GMTs) Before and Post-vaccination With Either Fluzone Intradermal and Fluzone Intramuscular Vaccine. [Pre- and Day 28 post-vaccination]

   The serological determinations of total anti influenza antibodies were performed using an Hemagglutinin inhibition (HAI) test.

2. Number of Participants Reporting a Solicited Injection Site or Systemic Reaction, Post Vaccination With Either Fluzone Intradermal or Fluzone Intramuscular Vaccine [Day 0 up to 7 days post-vaccination]

   Solicited injection site reactions: Pain, Erythema, Swelling, Induration, Ecchymosis, and Pruritus. Solicited systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Aged ≥ 65 years on the day of vaccination.

• Informed consent form signed.

• Medically stable (Subjects may have underlying illnesses such as hypertension, diabetes, ischemic heart disease, congestive cardiac disorders or hypothyroidism, as long as their symptoms/signs are controlled).

• Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

• Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to the standard-dose Fluzone® vaccine or a vaccine containing the same substances (the list of vaccine components is included in the Investigator's Brochure).

• Congenital or history of acquired immunodeficiency, or immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months.

• Systemic corticosteroid therapy as follows:

• Continuous use with a dosage equivalent to > 15 mg/day of oral prednisone for 90 days preceding vaccination

• Sporadic use with a dose of > 40 mg/day of oral prednisone for > 14 days in the 90 days preceding vaccination.

Note: Use of topical or inhalant corticosteroids is acceptable.

• Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that is stable at the time of vaccination in the absence of therapy, as well as subjects who have a history of neoplastic disease and who have been disease-free for ≥ 5 years).

• Current abuse of alcohol or drug addiction that may interfere with the subject's ability to comply with trial procedures.

• Receipt of blood or blood-derived products in the past 3 months.

• Vaccination against influenza in the past 6 months.

• Any vaccination in the 4 weeks preceding the trial vaccination.

• Vaccination planned in the 4 weeks following the trial vaccination.

• Participation in another clinical trial in the 4 weeks preceding trial vaccination.

• Planned participation in another clinical trial during the present trial period. Concomitant participation in an observational trial (not involving drugs, vaccines, or medical devices) is acceptable.

• Chronic illness at a stage that could interfere with trial conduct or completion.

• Known current HIV, hepatitis B (HBsAg) or hepatitis C infection or seropositivity.

• Known thrombocytopenia or bleeding disorder contraindicating IM vaccination.

• Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.

• Acute illness and febrile illness with a temperature ≥ 38.0°C [or 100.4°F]) 72 hours before or on the day of inclusion.

• Received antibiotics therapy within 72 hours preceding the trial vaccination.

• Received any allergy shots in the 7-day period preceding trial vaccination and/or scheduled to receive any allergy shots in the 7-day period after trial vaccination.

• Any condition, which in the opinion of the investigator would pose a health risk to the participant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Alabaster	Alabama	United States
2		Tucson	Arizona	United States
3		Fountain Valley	California	United States
4		Pinellas Park	Florida	United States
5		Chicago	Illinois	United States
6		Springfield	Missouri	United States
7		Brooklyn	New York	United States
8		New York	New York	United States
9		Bensalem	Pennsylvania	United States
10		Grove City	Pennsylvania	United States
11		Johnstown	Pennsylvania	United States
12		Pittsburgh	Pennsylvania	United States
13		Fort Worth	Texas	United States
14		Galveston	Texas	United States
15		Layton	Utah	United States
16		South Jordan	Utah	United States
17		Norfolk	Virginia	United States

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Medical Director, Sanofi Pasteur Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00388583
• Other Study ID Numbers: FID04
• First Posted: Oct 17, 2006
• Last Update Posted: Apr 18, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by Sanofi: Influenza; Orthomyxoviruses; Inactivated Split-virion influenza vaccine; Elderly.
• Additional relevant MeSH terms: Infections; Communicable Diseases; Influenza, Human; Orthomyxoviridae Infections; Vaccines

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 28 September 2006 through 30 May 2007 in 16 clinics in the US
Pre-assignment Detail	A total of 816 of the 817 participants that met the inclusion and exclusion criteria were enrolled and vaccinated. Data on the 807 participants that completed the study are presented.

Arm/Group Title	Fluzone Intradermal (ID) Vaccine Group	Fluzone Intramuscular (IM) Vaccine Group
Arm/Group Description	Participants received a dose of Fluzone Intradermal vaccine on Day 0	Participants received a dose of Fluzone Intramuscular vaccine on Day 0
Period Title: Overall Study
STARTED	407	410
COMPLETED	401	406
NOT COMPLETED	6	4

Baseline Characteristics

Arm/Group Title	Fluzone ID Vaccine Group	Fluzone IM Vaccine Group	Total
Arm/Group Description	Participants received a dose (0.1 mL) of Fluzone intradermal vaccine on Day 0.	Participants received a dose (0.5 mL) of Fluzone intramuscular vaccine on Day 0.	Total of all reporting groups
Overall Participants	401	406	807
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	401 100%	406 100%	807 100%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	72.8 (6.08)	72.3 (5.83)	72.5 (5.955)
Sex: Female, Male (Count of Participants)
Female	234 58.4%	223 54.9%	457 56.6%
Male	167 41.6%	183 45.1%	350 43.4%
Region of Enrollment (Number) [Number]
United States	401 100%	406 100%	807 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With at Least a 4-Fold Increase in Serum HAI Antibody Titer Post-vaccination With Either Fluzone Intradermal or Fluzone Intramuscular Vaccine.
Description	The serological determinations of total anti-influenza antibodies were performed using an Hemagglutinin inhibition (HAI) test.
Time Frame	Pre-vaccination and Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Immunogenicity determination was in all per protocol population

Arm/Group Title	Fluzone Intradermal (ID) Vaccine Group	Fluzone Intramuscular (IM) Vaccine Group
Arm/Group Description	Participants received a dose of Fluzone Intradermal vaccine on Day 0	Participants received a dose of Fluzone Intramuscular vaccine on Day 0
Measure Participants	401	406
A/H1N1 Serogroup (N = 400, 406)	119 29.7%	105 25.9%
A/H3N2 Serogroup (N = 398, 404)	235 58.6%	222 54.7%
B Serogroup (N = 400, 405)	105 26.2%	103 25.4%

2. Secondary Outcome

Title	Geometric Mean Antibody Titers (GMTs) Before and Post-vaccination With Either Fluzone Intradermal and Fluzone Intramuscular Vaccine.
Description	The serological determinations of total anti influenza antibodies were performed using an Hemagglutinin inhibition (HAI) test.
Time Frame	Pre- and Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Immunogenicity determination was in all per protocol population

Arm/Group Title	Fluzone Intradermal (ID) Vaccine Group	Fluzone Intramuscular (IM) Vaccine Group
Arm/Group Description	Participants received a dose of Fluzone Intradermal vaccine on Day 0	Participants received a dose of Fluzone Intramuscular vaccine on Day 0
Measure Participants	401	406
A/H1N1 Serogroup (Pre-vaccination)	27.46	24.86
A/H1N1 Serogroup (Post-vaccination)	71.17	59.04
A/H3N2 Serogroup (Pre-vaccination)	75.95	64.95
A/H3N2 Serogroup (Post-vaccination)	500.65	360.42
B Serogroup (Pre-vaccination)	13.11	12.95
B Serogroup (Post-vaccination)	35.06	35.77

3. Primary Outcome

Title	Number of Participants Who Achieved Seroprotection Post-vaccination With Either Fluzone Intradermal or Fluzone Intramuscular Vaccine.
Description	Seroprotection was defined as a post-vaccination Hemagglutinin inhibition (HAI) antibody titer ≥ 40
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Immunogenicity determination was in all per protocol population

Arm/Group Title	Fluzone Intradermal (ID) Vaccine Group	Fluzone Intramuscular (IM) Vaccine Group
Arm/Group Description	Participants received a dose of Fluzone Intradermal vaccine on Day 0	Participants received a dose of Fluzone Intramuscular vaccine on Day 0
Measure Participants	401	406
A/H1N1 Serogroup (N = 400, 406)	303 75.6%	292 71.9%
A/H3N2 Serogroup (N = 398, 405)	391 97.5%	389 95.8%
B Serogroup (N = 400, 406)	200 49.9%	213 52.5%

4. Secondary Outcome

Title	Number of Participants Reporting a Solicited Injection Site or Systemic Reaction, Post Vaccination With Either Fluzone Intradermal or Fluzone Intramuscular Vaccine
Description	Solicited injection site reactions: Pain, Erythema, Swelling, Induration, Ecchymosis, and Pruritus. Solicited systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia.
Time Frame	Day 0 up to 7 days post-vaccination

Outcome Measure Data

Analysis Population Description

Safety analysis was on all enrolled and vaccinated participants, intend-to-treat population

Arm/Group Title	Fluzone Intradermal (ID) Vaccine Group	Fluzone Intramuscular (IM) Vaccine Group
Arm/Group Description	Participants received a dose of Fluzone Intradermal vaccine on Day 0	Participants received a dose of Fluzone Intramuscular vaccine on Day 0
Measure Participants	407	409
Any Injection Site Pain	105 26.2%	98 24.1%
Grade 3 Injection Site Pain (Incapacitating)	0 0%	1 0.2%
Any Injection Site Erythema	282 70.3%	49 12.1%
Grade 3 Injection Site Erythema (≥ 5 cm)	39 9.7%	0 0%
Any Injection Site Swelling	186 46.4%	20 4.9%
Grade 3 Injection Site Swelling (≥ 5 cm)	17 4.2%	4 1%
Any Injection Site Induration	178 44.4%	17 4.2%
Grade 3 Injection Site Induration (≥ 5 cm)	12 3%	0 0%
Any Injection Site Ecchymosis	23 5.7%	12 3%
Grade 3 Injection Site Ecchymosis (Incapacitating)	1 0.2%	0 0%
Any Injection Site Pruritus	137 34.2%	23 5.7%
Grade 3 Injection Site Pruritus (Incapacitating)	0 0%	0 0%
Any Solicited Fever	10 2.5%	4 1%
Grade 3 Solicited Fever (>102.2°F)	0 0%	1 0.2%
Any Solicited Headache	69 17.2%	63 15.5%
Gr 3 Solicited Headache- Prevents daily activities	2 0.5%	1 0.2%
Any Solicited Malaise	57 14.2%	41 10.1%
Grd 3 Solicited Malaise- Prevents daily activities	3 0.7%	4 1%
Any Solicited Myalgia	68 17%	56 13.8%
Grd 3 Solicited Myalgia- Prevents daily activities	4 1%	0 0%

Adverse Events

Time Frame	Adverse events data were collected from the day of vaccination up to 6 months post-vaccination.
Arm/Group Title	Fluzone Intradermal (ID) Vaccine Group		Fluzone Intramuscular (IM) Vaccine Group
Arm/Group Description	Participants received a dose of Fluzone Intradermal vaccine on Day 0		Participants received a dose of Fluzone Intramuscular vaccine on Day 0
All Cause Mortality
	Fluzone Intradermal (ID) Vaccine Group		Fluzone Intramuscular (IM) Vaccine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fluzone Intradermal (ID) Vaccine Group		Fluzone Intramuscular (IM) Vaccine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/407 (8.1%)		34/409 (8.3%)
Blood and lymphatic system disorders
Anaemia	1/407 (0.2%)	2	0/409 (0%)	0
Cardiac disorders
Coronary artery disease	2/407 (0.5%)	4	2/409 (0.5%)	2
Atrial fibrillation	1/407 (0.2%)	1	1/409 (0.2%)	1
Angina pectoris	1/407 (0.2%)	1	0/409 (0%)	0
Ischaemic cardiomyopathy	1/407 (0.2%)	3	1/409 (0.2%)	3
Myocardial infarction	0/407 (0%)	0	0/0 (NaN)	0
Ischaemic cardiomyopathy	0/407 (0%)	0	1/409 (0.2%)	1
Pericarditis	0/407 (0%)	0	1/409 (0.2%)	1
Mitral valve incompetence	0/407 (0%)	0	1/409 (0.2%)	1
Arrhythmia	0/407 (0%)	0	1/409 (0.2%)	1
Acute coronary syndrome	0/407 (0%)	0	1/409 (0.2%)	1
Cardiac failure congestive	0/407 (0%)	0	2/409 (0.5%)	2
Atrial tachycardia	0/407 (0%)	0	1/409 (0.2%)	1
Gastrointestinal disorders
Enterovesical Fistula	1/407 (0.2%)	1	0/409 (0%)	0
Chest Pain	1/407 (0.2%)	1	0/409 (0%)	0
Small intestinal obstruction	1/407 (0.2%)	1	0/409 (0%)	0
Diverticulum	1/407 (0.2%)	1	0/409 (0%)	0
Hemorrhoids	1/407 (0.2%)	1	0/409 (0%)	0
Ileus	0/407 (0%)	0	0/409 (0%)	0
Colitis	0/407 (0%)	0	0/409 (0%)	0
Pancreatitis	0/407 (0%)	0	1/409 (0.2%)	1
Inguinal hernia	0/407 (0%)	0	1/409 (0.2%)	1
Peptic ulcer	0/407 (0%)	0	1/409 (0.2%)	1
Small intestine obstruction	0/407 (0%)	0	1/409 (0.2%)	1
General disorders
Chest pain	0/407 (0%)	0	1/409 (0.2%)	1
Hepatobiliary disorders
Bile duct stone	0/407 (0%)	0	1/409 (0.2%)	1
Infections and infestations
Incision site infection	1/407 (0.2%)	1	0/409 (0%)	0
Bronchitis acute	1/407 (0.2%)	1	0/409 (0%)	0
Pneumonia	1/407 (0.2%)	2	0/409 (0%)	0
Tracheobronchitis	0/407 (0%)	0	1/409 (0.2%)	1
Injury, poisoning and procedural complications
Fall	1/407 (0.2%)	1	0/409 (0%)	0
Femur fracture	1/407 (0.2%)	1	1/409 (0.2%)	2
Device electric finding	0/407 (0%)	0	1/409 (0.2%)	1
Metabolism and nutrition disorders
Hypoglycaemia	1/407 (0.2%)	1	0/409 (0%)	0
Diabetes mellitus	1/407 (0.2%)	1	0/409 (0%)	0
Diabetes mellitus non insulin dependent	0/407 (0%)	0	1/409 (0.2%)	1
Musculoskeletal and connective tissue disorders
Scoliosis	1/407 (0.2%)	1	0/409 (0%)	0
Shoulder pain	1/407 (0.2%)	1	0/409 (0%)	0
Rotator cuff syndrome	1/407 (0.2%)	1	0/409 (0%)	0
Osteoarthritis	1/407 (0.2%)	1	2/409 (0.5%)	2
Joint instability	0/407 (0%)	0	1/409 (0.2%)	1
Intervertebral disc protrusion	0/407 (0%)	0	1/409 (0.2%)	1
Back pain	0/407 (0%)	0	1/409 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	1/407 (0.2%)	1	1/409 (0.2%)	1
Colon cancer	1/407 (0.2%)	1	0/409 (0%)	0
Lung neoplasm malignant	1/407 (0.2%)	1	1/409 (0.2%)	2
Benign renal neoplasm	1/407 (0.2%)	1	0/409 (0%)	0
Uterine cancer	1/407 (0.2%)	1	0/409 (0%)	0
Squamous cell carcinoma of the skin	0/407 (0%)	0	0/0 (NaN)	0
Basal cell carcinoma	0/407 (0%)	0	0/409 (0%)	0
Nervous system disorders
Cerebrovascular accident	3/407 (0.7%)	7	1/409 (0.2%)	1
Dizziness	0/407 (0%)	0	1/409 (0.2%)	1
Transient ischaemic attack	0/407 (0%)	0	1/409 (0.2%)	1
Renal and urinary disorders
Nephrolithiasis	2/407 (0.5%)	2	0/409 (0%)	0
Renal failure acute	0/407 (0%)	0	1/409 (0.2%)	1
Bladder prolapse	0/407 (0%)	0	1/409 (0.2%)	1
Urinary retention	0/407 (0%)	0	1/409 (0.2%)	1
Reproductive system and breast disorders
Cystocele	0/407 (0%)	0	0/409 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/407 (0.2%)	4	0/409 (0%)	0
Chronic obstructive pulmonary disease	1/407 (0.2%)	2	1/409 (0.2%)	1
Pulmonary embolism	1/407 (0.2%)	1	0/409 (0%)	0
Atelectasis	0/407 (0%)	0	1/409 (0.2%)	1
Surgical and medical procedures
Transuerethral prostatectomy	0/407 (0%)	0	1/409 (0.2%)	1
Vascular disorders
Leriche syndrome	1/407 (0.2%)	1	0/409 (0%)	0
Deep vein thrombosis	0/407 (0%)	0	1/409 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Fluzone Intradermal (ID) Vaccine Group		Fluzone Intramuscular (IM) Vaccine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	282/407 (69.3%)		98/409 (24%)
General disorders
Vessel puncture site bruise	23/407 (5.7%)	23	15/409 (3.7%)	15
Solicited injection site pain	105/402 (26.1%)	105	98/409 (24%)	98
Solicited injection site erythema	282/402 (70.1%)	282	49/409 (12%)	49
Solicited injection site induration	178/400 (44.5%)	178	17/409 (4.2%)	17
Solicited injection site ecchymosis	23/400 (5.8%)	23	12/409 (2.9%)	12
Solicited injection site pruritus	137/402 (34.1%)	137	23/409 (5.6%)	23
Solicited malaise	57/402 (14.2%)	57	41/409 (10%)	41
Solicited myalgia	68/402 (16.9%)	68	56/409 (13.7%)	56
Solicited injection site swelling	186/402 (46.3%)	186	20/409 (4.9%)	20
Nervous system disorders
Solicited headache (Pyrexia)	69/402 (17.2%)	69	63/409 (15.4%)	63

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.