Safety and Immunogenicity of Surface Antigen, Inactivated, Adjuvanted With MF59C.1 Influenza Vaccine, Formulation 2008-2009

• Sponsor: Novartis Vaccines (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00734734
• Collaborator: (none)
• Enrollment: 64
• Locations: 2
• Arm: 1
• Duration (Days): 30
• Patients Per Site: 32
• Patients Per Site Per Month: 32.5

Study Details

Study Description

Brief Summary

Trial for annual approval of interpandemic influenza vaccines

Condition or Disease	Intervention/Treatment	Phase
Interpandemic Influenza	Biological: Seasonal Influenza Vaccine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase II, Open Label, Uncontrolled, Multi Center Study to Evaluate Safety and Immunogenicity of FLUAD® Surface Antigen, Inactivated, Adjuvanted With MF59C.1 Influenza Vaccine, Formulation 2008-2009, When Administered to Elderly Subjects
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Biological: Seasonal Influenza Vaccine; 1 single intramuscular dose of influenza vaccine, 2008/2009 NH formulation

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved Seroconversion or Significant Increase in Single Radial Hemolysis (SRH) Area Against Each of Three Vaccine Strains After One Vaccination of FLUAD [day 21]

   Immunogenicity was measured as the percentage of participants who achieved seroconversion or significant increase in single radial hemolysis (SRH) area, against each of the three vaccine strains, three weeks after vaccination (day 21), evaluated using SRH assay. Seroconversion: proportion of participants with negative pre-vaccination serum and a post-vaccination serum area ≥ 25 mm2. Significant increase: proportion of participants with at least a 50% increase in area from positive pre-vaccination serum. Seroconversion or significant increase: proportion of participants with either seroconversion or significant increase. The European (Committee for Medicinal Products for Human Use [CHMP]) criterion is met, if percentage of participants achieving seroconversion or significant increase in SRH area is 30% (≥65 years).

2. Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD [day 21]

   Geometric mean ratio (GMR) of participants was calculated as the ratio of post-vaccination to pre-vaccination SRH geometric mean areas (GMAs), directed against each of the three vaccine strains, three weeks after FLUAD vaccination (day 21). The CHMP criterion was met if the geometric mean increase (GMR, day 21/day 0) in SRH antibody area is >2.0 (≥65 years).

3. Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD [day 21]

   Immunogenicity was measured as the percentage of participants achieving SRH area ≥25 mm2 against each of the three vaccine strains at baseline (day 0) and three weeks after FLUAD vaccination (day 21). This criterion is met according to CHMP guideline if percentage of participants achieving SRH area ≥25 mm2 is 60% (≥65 years).

4. Number of Participants Who Reported Solicited Local and Systemic Reactions [0 to 3 days post-vaccination]

   Safety was assessed for participants who reported solicited local and systemic reactions from day 0 up to and including day 3 after the FLUAD vaccination.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• 65 years of age or older

• Mentally competent

• Willing and able to give written informed consent prior to study entry

• Able to comply with all the study requirements

• In general good health

Key Exclusion Criteria:

• Any serious chronic or acute disease

• History of any anaphylactic reaction and/or serious allergic reaction following a vaccination, a proven hypersensitivity to any component of the study vaccine (e.g. to ovalbumin, chicken protein, chicken feathers, influenza viral protein, kanamycin and neomycin sulphate);

• Known or suspected (or have a high risk of developing) impairment/alteration of immune function (excluding that normally associated with advanced age)

• Receipt of parenteral immunoglobulin preparation, blood products and/or plasma derivates within the past 3 months and for the full length of the study; suspected or known HIV infection or HIV-related disease

• A bleeding diathesis or condition associated with prolonged bleeding time that in the investigator's opinion would interfere with the safety of the subject

• Within the past 12 months, they have received more than one injection of influenza vaccine

• Within the past 6 months, participants had laboratory confirmed influenza disease; received influenza vaccine

• Within the past 4 weeks participants had received another vaccine; any investigational agent

• An acute exacerbation of a COPD (chronic obstructive pulmonary disease) within the past 14 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ufficio Igiene e Sanità Pubblica di Lanciano, ASL Lanciano - Vasto, sede legale	Lanciano		Italy	66034
2	Pianiga Distretto n. 2 - Area Sud - Azienda ULSS 13 Mirano -Via Nazionale 48	Pianiga		Italy	30034

Sponsors and Collaborators

• Novartis Vaccines

Investigators

• Study Chair: Novartis Vaccines, Novartis Vaccines

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Vaccines
• ClinicalTrials.gov Identifier: NCT00734734
• Other Study ID Numbers: V70P7S; 2008-001047-19
• First Posted: Aug 14, 2008
• Last Update Posted: Jan 28, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Novartis Vaccines: Prophylaxis of Influenza; Influenza Vaccines; MF59C.1
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	Overall, 64 participants ≥65 years of age were enrolled at 2 sites in Italy.
Pre-assignment Detail	Blood samples for the determination of antibody titers were drawn on Day 0 prior to vaccination.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single intramuscular (IM) 0.5 milliliter (mL) dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Period Title: Overall Study
STARTED	64
COMPLETED	64
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Overall Participants	64
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	73.1 (4.8)
Sex: Female, Male (Count of Participants)
Female	32 50%
Male	32 50%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved Seroconversion or Significant Increase in Single Radial Hemolysis (SRH) Area Against Each of Three Vaccine Strains After One Vaccination of FLUAD
Description	Immunogenicity was measured as the percentage of participants who achieved seroconversion or significant increase in single radial hemolysis (SRH) area, against each of the three vaccine strains, three weeks after vaccination (day 21), evaluated using SRH assay. Seroconversion: proportion of participants with negative pre-vaccination serum and a post-vaccination serum area ≥ 25 mm2. Significant increase: proportion of participants with at least a 50% increase in area from positive pre-vaccination serum. Seroconversion or significant increase: proportion of participants with either seroconversion or significant increase. The European (Committee for Medicinal Products for Human Use [CHMP]) criterion is met, if percentage of participants achieving seroconversion or significant increase in SRH area is 30% (≥65 years).
Time Frame	day 21

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set included all enrolled participants who had received the relevant dose of vaccine correctly on Day 0, provided evaluable serum samples with the relevant time windows, and had no major protocol violations.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Measure Participants	64
A/H1N1	38 59.4%
A/H3N2	55 85.9%
B	42 65.6%

2. Primary Outcome

Title	Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD
Description	Geometric mean ratio (GMR) of participants was calculated as the ratio of post-vaccination to pre-vaccination SRH geometric mean areas (GMAs), directed against each of the three vaccine strains, three weeks after FLUAD vaccination (day 21). The CHMP criterion was met if the geometric mean increase (GMR, day 21/day 0) in SRH antibody area is >2.0 (≥65 years).
Time Frame	day 21

Outcome Measure Data

Analysis Population Description

Analysis was done using PP set.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Measure Participants	64
A/H1N1	1.87
A/H3N2	3.74
B	2.38

3. Primary Outcome

Title	Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD
Description	Immunogenicity was measured as the percentage of participants achieving SRH area ≥25 mm2 against each of the three vaccine strains at baseline (day 0) and three weeks after FLUAD vaccination (day 21). This criterion is met according to CHMP guideline if percentage of participants achieving SRH area ≥25 mm2 is 60% (≥65 years).
Time Frame	day 21

Outcome Measure Data

Analysis Population Description

Analysis was done using PP set.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Measure Participants	64
A/H1N1	89 139.1%
A/H3N2	75 117.2%
B	80 125%

4. Primary Outcome

Title	Number of Participants Who Reported Solicited Local and Systemic Reactions
Description	Safety was assessed for participants who reported solicited local and systemic reactions from day 0 up to and including day 3 after the FLUAD vaccination.
Time Frame	0 to 3 days post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 3.
Measure Participants	64
Injection site ecchymosis (N= 59)	0 0%
Injection site erythema (N= 64)	10 15.6%
Injection site induration (N= 64)	2 3.1%
Injection site swelling (N= 59)	0 0%
Injection site pain (N= 64)	11 17.2%
Chills shivering (N= 64)	0 0%
Malaise (N= 64)	0 0%
Myalgia (N= 64)	1 1.6%
Arthralgia (N= 64)	0 0%
Headache (N= 64)	2 3.1%
Sweating (N= 64)	1 1.6%
Fatigue (N= 64)	2 3.1%
Fever (≥38°C) (N= 64)	0 0%

Adverse Events

Time Frame	From Day 0 through Day 21.
Adverse Event Reporting Description	Adverse events other than local and systemic reactions or solicited reactions lasting longer than 3 days after vaccination were documented during the study period. Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.
Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
All Cause Mortality
	FLUAD
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	FLUAD
	Affected / at Risk (%)	# Events
Total	0/64 (0%)
Other (Not Including Serious) Adverse Events
	FLUAD
	Affected / at Risk (%)	# Events
Total	4/64 (6.3%)
General disorders
Induration	1/64 (1.6%)
Injection site erythema	1/64 (1.6%)
Musculoskeletal and connective tissue disorders
Myalgia	1/64 (1.6%)
Nervous system disorders
Headache	1/64 (1.6%)
Skin and subcutaneous tissue disorders
Erythema	2/64 (3.1%)
Hyperhidrosis	1/64 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreement with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publications of the pooled data (i.e., data from all sites) in the clinical trial.