Immunogenicity of a Split, Cell-Based, Inactivated, Trivalent Influenza Vaccine in Healthy Adult Subjects

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00845429
• Collaborator: (none)
• Enrollment: 729
• Locations: 15
• Arms: 3
• Duration (Months): 13
• Patients Per Site: 48.6
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

Primary Objective:

To describe the immune response to a single administration of 2 formulations of the investigational cell-based influenza vaccines in healthy adult subjects.

Secondary Objective:

To describe the safety following a single administration of 2 formulations of the investigational cell-based influenza vaccines in healthy adult subjects.

Condition or Disease	Intervention/Treatment	Phase
Influenza; Orthomyxoviruses; Myxovirus Infection	Biological: Influenza virus vaccine - cell based (2007-2008 Formulation); Biological: Influenza virus vaccine - cell-based (2007-2008 Formulation); Biological: Influenza virus vaccine (2007-2008 Formulation)	Phase 2

Detailed Description

This is a multi-center study in healthy adult subjects. All subjects will receive a single dose of one of the influenza vaccine formulations and will provide blood samples for immunogenicity assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 729 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Immunogenicity of Two Dosages of a Split, Cell-Based, Inactivated, Trivalent Influenza Vaccine Administered in Healthy Adult Subjects Aged 18 to 49 Years
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: Standard-dose Cell-based Influenza Vaccine Participants will receive a single dose of standard-dose cell-based influenza virus vaccine.	Biological: Influenza virus vaccine - cell based (2007-2008 Formulation); 0.5 mL, Intramuscular
Experimental: Group 2: High-dose Cell-based Influenza Vaccine Participants will receive a single dose of high-dose cell-based influenza virus vaccine.	Biological: Influenza virus vaccine - cell-based (2007-2008 Formulation); 1.0 mL, Intramuscular
Active Comparator: Group 3: Licensed Fluzone® Influenza Vaccine Participants will receive a single dose of licensed Fluzone® influenza vaccine.	Biological: Influenza virus vaccine (2007-2008 Formulation); 0.5 mL, Intramuscular; Other Names: Fluzone® (2007-2008 formulation)

Outcome Measures

Primary Outcome Measures

1. Summary of the Pre- and Post-Vaccination Geometric Mean Titers (GMTs) for Each of the Influenza Vaccine Antigens. [Days 0 and 21 post-vaccination]

2. Percentage of Participants With Seroprotection to Each of the Influenza Vaccine Antigen Before and Post-vaccination. [Day 21 post-vaccination]

   Seroprotection was defined as a titer ≥ 40 1/dil, and determined in participants with a valid serology result for the particular Flu strain, including results reported as less than lower limit of quantitation (LLOQ)

3. Percentage of Participants Achieving Seroconversion or Significant Increase at Day 21 Following Vaccination With Influenza Vaccine. [Day 21 post-vaccination]

   Seroconversion: For participants with a Day 0 pre-vaccination titer < 10 (1/dil), titer ≥ 40 (1/dil) on Day 21. Significant Increase: For participants with a Day 0 pre-vaccination titer ≥ 10 (1/dil), ≥ 4-fold increase of titer on Day 21.

Secondary Outcome Measures

1. Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With Influenza Vaccine. [Day 0 up to Day 7 post-vaccination]

   Solicited Injection Site Reactions: Pain, erythema or redness, swelling, ecchymosis, and induration. Solicited Systemic Reactions: Fever (temperature), headache, malaise, myalgia, and rigors.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria :

• Healthy male or female subject, aged ≥ 18 to < 50 years on the day of inclusion

• Informed consent form signed

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

• For a woman of childbearing potential: a negative urine pregnancy test and documented use of an effective method of contraception or abstinence for at least four weeks pre vaccination and up until three weeks post-vaccination

Exclusion Criteria :

• Subject currently breast-feeding.

• Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the trial vaccination.

• Planned participation in another clinical trial during the present trial period.

• Prior participation in the Phase I trial of FLU INTERPAN (PER.C6) vaccine (study GCE01).

• 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 except the use of topical or inhalant corticosteroids

• Systemic hypersensitivity to egg proteins, chicken proteins, or to any of the vaccine components, or history of a life-threatening reaction to the trial vaccine or a vaccine containing the same substances.

• Chronic illness at a stage that could interfere with trial conduct or completion (chronic illness may include, but is not limited to, cardiac, renal or auto-immune disorders, or diabetes).

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

• Receipt of any vaccination in the 4 weeks preceding vaccination, or planned receipt of any vaccination in the 4 weeks following the trial vaccination.

• History of influenza infection (confirmed either clinically, serologically or microbiologically) within the 6 months preceding vaccination.

• Previous vaccination against influenza (in the 6 months preceding the trial vaccination).

• Planned receipt of any other 2007-2008 influenza vaccine.

• Thrombocytopenia or bleeding disorder contraindicating intramuscular (IM) vaccination.

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

• History of Guillain-Barré syndrome

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

• Any other condition which in the opinion of the investigator would pose a health risk to the participant or interfere with the evaluation of the vaccine.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Hoover	Alabama	United States	35216
2		Mobile	Alabama	United States	36608
3		Tucson	Arizona	United States	85710
4		Milford	Connecticut	United States	06460
5		Pinellas Park	Florida	United States	33781
6		Chicago	Illinois	United States	60610
7		Wichita	Kansas	United States	67207
8		Kansas City	Missouri	United States	64114
9		Springfield	Missouri	United States	65802
10		Cary	North Carolina	United States	27518
11		Raleigh	North Carolina	United States	27609
12		Cincinnati	Ohio	United States	45249
13		Bensalem	Pennsylvania	United States	19020
14		Warwick	Rhode Island	United States	02886
15		Mt Pleasant	South Carolina	United States	29464

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: NCT00845429
• Other Study ID Numbers: GCE03
• First Posted: Feb 18, 2009
• Last Update Posted: Dec 19, 2012
• Last Verified: Dec 1, 2012

• Keywords provided by Sanofi: Influenza; Orthomyxoviruses; Split-virion inactivated influenza vaccine; cell-based vaccine; Adults
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 16 to 23 October 2007 in 15 clinical centers in the US.
Pre-assignment Detail	A total of 729 participants who met the inclusion, but no exclusion criteria were enrolled and vaccinated.

Arm/Group Title	Group 1: Standard Dose Cell-Based Influenza Vaccine	Group 2: High-dose Cell-Based Influenza Vaccine	Group 3: Licensed Fluzone® Influenza Vaccine
Arm/Group Description	Participants received a single dose of standard-dose cell-based influenza vaccine; 0.5 ml, intramuscularly.	Participants received a single dose of high-dose cell-based influenza vaccine; 1.0 ml, intramuscularly.	Participants received a single dose of licensed Fluzone® influenza vaccine; 0.5 ml, intramuscularly.
Period Title: Overall Study
STARTED	244	241	244
COMPLETED	230	226	224
NOT COMPLETED	14	15	20

Baseline Characteristics

Arm/Group Title	Group 1: Standard Dose Cell-Based Influenza Vaccine	Group 2: High-dose Cell-Based Influenza Vaccine	Group 3: Licensed Fluzone® Influenza Vaccine	Total
Arm/Group Description	Participants received a single dose of standard-dose cell-based influenza vaccine; 0.5 ml, intramuscularly.	Participants received a single dose of high-dose cell-based influenza vaccine; 1.0 ml, intramuscularly.	Participants received a single dose of licensed Fluzone® influenza vaccine; 0.5 ml, intramuscularly.	Total of all reporting groups
Overall Participants	244	241	244	729
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	244 100%	241 100%	244 100%	729 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.4 (9.41)	34.5 (9.18)	34.1 (9.42)	34.3 (9.32)
Sex: Female, Male (Count of Participants)
Female	158 64.8%	162 67.2%	151 61.9%	471 64.6%
Male	86 35.2%	79 32.8%	93 38.1%	258 35.4%
Region of Enrollment (participants) [Number]
United States	244 100%	241 100%	244 100%	729 100%

Outcome Measures

1. Primary Outcome

Title	Summary of the Pre- and Post-Vaccination Geometric Mean Titers (GMTs) for Each of the Influenza Vaccine Antigens.
Time Frame	Days 0 and 21 post-vaccination

Outcome Measure Data

Analysis Population Description

Geometric mean titers were assessed in the full analysis set population.

Arm/Group Title	Group 1: Standard Dose Cell-Based Influenza Vaccine	Group 2: High-dose Cell-Based Influenza Vaccine	Group 3: Licensed Fluzone® Influenza Vaccine
Arm/Group Description	Participants received a single dose of standard-dose cell-based influenza vaccine; 0.5 ml, intramuscularly.	Participants received a single dose of high-dose cell-based influenza vaccine; 1.0 ml, intramuscularly.	Participants received a single dose of licensed Fluzone® influenza vaccine; 0.5 ml, intramuscularly.
Measure Participants	236	233	238
A/H1N1: Solomon Islands, Day 0 (N = 236, 231, 237)	25.9	26.4	26.6
A/H1N1: Solomon Islands, Day 21 (N= 236, 232, 238)	184.8	226.6	425.1
A/H3N2: Wisconsin, Day 0 (N = 236, 232, 237)	51.2	53.4	51.5
A/H3N2: Wisconsin, Day 21 (N = 236, 230, 238)	288.3	351.3	692.4
B: Malaysia, Day 0 (N = 236, 233, 238)	13.4	14.3	14.2
B: Malaysia, Day 21 (nN= 235, 233, 237)	51.1	53.0	108.6

2. Primary Outcome

Title	Percentage of Participants With Seroprotection to Each of the Influenza Vaccine Antigen Before and Post-vaccination.
Description	Seroprotection was defined as a titer ≥ 40 1/dil, and determined in participants with a valid serology result for the particular Flu strain, including results reported as less than lower limit of quantitation (LLOQ)
Time Frame	Day 21 post-vaccination

Outcome Measure Data

Analysis Population Description

Seroprotection was assessed in the full analysis set population.

Arm/Group Title	Group 1: Standard Dose Cell-Based Influenza Vaccine	Group 2: High-dose Cell-Based Influenza Vaccine	Group 3: Licensed Fluzone® Influenza Vaccine
Arm/Group Description	Participants received a single dose of standard-dose cell-based influenza vaccine; 0.5 ml, intramuscularly.	Participants received a single dose of high-dose cell-based influenza vaccine; 1.0 ml, intramuscularly.	Participants received a single dose of licensed Fluzone® influenza vaccine; 0.5 ml, intramuscularly.
Measure Participants	236	233	238
A/H1N1: Solomon Islands Day 0 (N = 236, 231, 237)	40 16.4%	39 16.2%	41 16.8%
A/H1N1: Solomon Islands Day 21 (N = 236, 232, 238)	86 35.2%	90 37.3%	98 40.2%
A/H3N2: Wisconsin Day 0 (N = 236, 232, 237)	54 22.1%	62 25.7%	55 22.5%
A/H3N2: Wisconsin Day 21 (N = 236, 230, 238)	94 38.5%	98 40.7%	99 40.6%
B: Malaysia Day 0 (N = 236, 233, 238)	14 5.7%	20 8.3%	20 8.2%
B: Malaysia Day 21 (N = 235, 233, 237)	60 24.6%	64 26.6%	87 35.7%

3. Primary Outcome

Title	Percentage of Participants Achieving Seroconversion or Significant Increase at Day 21 Following Vaccination With Influenza Vaccine.
Description	Seroconversion: For participants with a Day 0 pre-vaccination titer < 10 (1/dil), titer ≥ 40 (1/dil) on Day 21. Significant Increase: For participants with a Day 0 pre-vaccination titer ≥ 10 (1/dil), ≥ 4-fold increase of titer on Day 21.
Time Frame	Day 21 post-vaccination

Outcome Measure Data

Analysis Population Description

Seroconversion and significant increase in Influenza vaccine antibodies were assessed in the full analysis set population.

Arm/Group Title	Group 1: Standard Dose Cell-Based Influenza Vaccine	Group 2: High-dose Cell-Based Influenza Vaccine	Group 3: Licensed Fluzone® Influenza Vaccine
Arm/Group Description	Participants received a single dose of standard-dose cell-based influenza vaccine; 0.5 ml, intramuscularly.	Participants received a single dose of high-dose cell-based influenza vaccine; 1.0 ml, intramuscularly.	Participants received a single dose of licensed Fluzone® influenza vaccine; 0.5 ml, intramuscularly.
Measure Participants	236	233	238
A/H1N1: Solomon Islands (N = 236, 231, 237)	54 22.1%	63 26.1%	74 30.3%
A/H3N2: Wisconsin (N = 236, 230, 237)	50 20.5%	53 22%	71 29.1%
B: Malaysia (N = 235, 233, 237)	38 15.6%	38 15.8%	61 25%

4. Secondary Outcome

Title	Number of Participants Reporting at Least 1 Solicited Injection Site or Systemic Reaction Post-vaccination With Influenza Vaccine.
Description	Solicited Injection Site Reactions: Pain, erythema or redness, swelling, ecchymosis, and induration. Solicited Systemic Reactions: Fever (temperature), headache, malaise, myalgia, and rigors.
Time Frame	Day 0 up to Day 7 post-vaccination

Outcome Measure Data

Analysis Population Description

Safety analysis was on all enrolled and vaccinated participants with available reaction data, intent-to-treat population.

Arm/Group Title	Group 1: Standard Dose Cell-Based Influenza Vaccine	Group 2: High-dose Cell-Based Influenza Vaccine	Group 3: Licensed Fluzone® Influenza Vaccine
Arm/Group Description	Participants received a single dose of standard-dose cell-based influenza vaccine; 0.5 ml, intramuscularly.	Participants received a single dose of high-dose cell-based influenza vaccine; 1.0 ml, intramuscularly.	Participants received a single dose of licensed Fluzone® influenza vaccine; 0.5 ml, intramuscularly.
Measure Participants	244	241	244
Any Solicited Injection Site Reaction	117 48%	156 64.7%	184 75.4%
Any Pain	103 42.2%	144 59.8%	175 71.7%
Grade 3 Pain (incapacitating, prevents activities)	1 0.4%	2 0.8%	1 0.4%
Any Erythema	36 14.8%	57 23.7%	55 22.5%
Grade 3 Erythema (≥ 5 cm)	0 0%	0 0%	4 1.6%
Any Swelling	24 9.8%	23 9.5%	36 14.8%
Grade 3 Swelling (≥ 5 cm)	0 0%	0 0%	1 0.4%
Any Ecchymosis	6 2.5%	19 7.9%	14 5.7%
Grade 3 Ecchymosis (≥ 5 cm)	0 0%	0 0%	1 0.4%
Any Induration	31 12.7%	29 12%	38 15.6%
Grade 3 Induration (≥ 5 cm)	0 0%	0 0%	0 0%
Any Solicited Systemic Reaction	114 46.7%	126 52.3%	137 56.1%
Any Fever	13 5.3%	9 3.7%	11 4.5%
Grade 3 Fever (39.0 ºC or 102.2 ºF)	0 0%	0 0%	2 0.8%
Any Headache	75 30.7%	85 35.3%	89 36.5%
Grade 3 Headache (Prevents daily activities)	3 1.2%	3 1.2%	6 2.5%
Any Malaise	58 23.8%	54 22.4%	63 25.8%
Grade 3 Malaise (Prevents daily activities)	6 2.5%	4 1.7%	5 2%
Any Myalgia	60 24.6%	70 29%	83 34%
Grade 3 Myalgia (Prevents daily activities)	1 0.4%	3 1.2%	4 1.6%
Any Rigors	16 6.6%	9 3.7%	13 5.3%
Grade 3 Rigors (Prevents daily activities)	2 0.8%	1 0.4%	1 0.4%

Adverse Events

Time Frame	Adverse events data were collected from the day of vaccination (Day 0) to up to 6 months post-vaccination.
Arm/Group Title	Group 1: Standard Dose Cell-Based Influenza Vaccine		Group 2: High-dose Cell-Based Influenza Vaccine		Group 3: Licensed Fluzone® Influenza Vaccine
Arm/Group Description	Participants received a single dose of standard-dose cell-based influenza vaccine; 0.5 ml, intramuscularly.		Participants received a single dose of high-dose cell-based influenza vaccine; 1.0 ml, intramuscularly.		Participants received a single dose of licensed Fluzone® influenza vaccine; 0.5 ml, intramuscularly.
All Cause Mortality
	Group 1: Standard Dose Cell-Based Influenza Vaccine		Group 2: High-dose Cell-Based Influenza Vaccine		Group 3: Licensed Fluzone® Influenza Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1: Standard Dose Cell-Based Influenza Vaccine		Group 2: High-dose Cell-Based Influenza Vaccine		Group 3: Licensed Fluzone® Influenza Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/244 (1.2%)		4/241 (1.7%)		6/244 (2.5%)
Hepatobiliary disorders
Biliary Dyskinesia	0/244 (0%)	0	0/241 (0%)	0	1/244 (0.4%)	1
Gallbladder Non-functioning	0/244 (0%)	0	1/241 (0.4%)	1	0/244 (0%)	0
Infections and infestations
Diverticulitis	1/244 (0.4%)	1	0/241 (0%)	0	0/244 (0%)	0
Gastroenteritis	1/244 (0.4%)	1	0/241 (0%)	0	1/244 (0.4%)	1
Injury, poisoning and procedural complications
Gastrointestinal Stoma Complication	0/244 (0%)	0	1/241 (0.4%)	1	0/244 (0%)	0
Pelvic Fracture	0/244 (0%)	0	0/241 (0%)	0	1/244 (0.4%)	1
Tibia Fracture	0/244 (0%)	0	1/241 (0.4%)	1	0/244 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/244 (0.4%)	1	0/241 (0%)	0	0/244 (0%)	0
Diabetic Ketoacidosis	0/244 (0%)	0	0/241 (0%)	0	1/244 (0.4%)	1
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion	0/244 (0%)	0	0/241 (0%)	0	1/244 (0.4%)	1
Nervous system disorders
Loss of Consciousness	0/244 (0%)	0	0/241 (0%)	0	1/244 (0.4%)	1
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous	0/244 (0%)	0	1/241 (0.4%)	1	0/244 (0%)	0
Psychiatric disorders
Depression	1/244 (0.4%)	1	0/241 (0%)	0	0/244 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/244 (0%)	0	1/241 (0.4%)	1	0/244 (0%)	0
Reproductive system and breast disorders
Ovarian Cyst Ruptured	0/244 (0%)	0	0/241 (0%)	0	1/244 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Group 1: Standard Dose Cell-Based Influenza Vaccine		Group 2: High-dose Cell-Based Influenza Vaccine		Group 3: Licensed Fluzone® Influenza Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	158/244 (64.8%)		179/241 (74.3%)		199/244 (81.6%)
General disorders
Injection site Pain	103/240 (42.9%)		144/234 (61.5%)		175/238 (73.5%)
Injection site Erythema	36/240 (15%)		57/234 (24.4%)		55/238 (23.1%)
Injection site Swelling	24/240 (10%)		23/234 (9.8%)		36/238 (15.1%)
Injection site Ecchymosis	6/240 (2.5%)		19/234 (8.1%)		14/238 (5.9%)
Injection site Induration	31/240 (12.9%)		29/234 (12.4%)		38/238 (16%)
Fever	13/240 (5.4%)		9/234 (3.8%)		11/238 (4.6%)
Malaise	58/240 (24.2%)		54/234 (23.1%)		63/238 (26.5%)
Rigors	16/240 (6.7%)		9/234 (3.8%)		13/238 (5.5%)
Musculoskeletal and connective tissue disorders
Myalgia	60/240 (25%)		70/234 (29.9%)		83/238 (34.9%)
Nervous system disorders
Headache	75/240 (31.3%)		85/234 (36.3%)		89/238 (37.4%)

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.