Study to Evaluate the Immunogenicity & Safety of an Investigational Influenza Vaccine (H1N1) in Adults

Influenza Clinical Trial

Official title:

Safety and Immunogenicity Study of GSK Biologicals' Influenza Vaccine GSK2340272A in Adults Aged 18 to 60 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00968539
• Other study ID #: 113456
• Secondary ID: 2009-013710-27
• Status: Completed
• Phase: Phase 3
• Start date: September 8, 2009
• Est. completion date: September 28, 2010

Study information

• Verified date: October 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of the study is to evaluate the immunogenicity and safety of GSK Biologicals' investigational vaccine GSK2340272A.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: September 28, 2010
• Est. primary completion date: September 28, 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• A male or female aged 18 to 60 years at the time of the first vaccination.

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol

• Written informed consent obtained from the subject.

• Satisfactory baseline medical assessment by history and physical examination. Stable health status is defined as the absence of health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within one month prior to enrollment.

• Access to a consistent means of telephone contact, which may be either in the home or at the workplace, land line or mobile, but NOT a pay phone or multiple-user device.

• Female subjects of non-childbearing potential may be enrolled in the study.

• Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.

• Female subjects of childbearing potential may be enrolled in the study, if the subject:

• has practiced adequate contraception for 30 days prior to vaccination, and

• has a negative pregnancy test on the day of vaccination, and

• has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of the study vaccine or planned use during the study period. Potential subjects in the follow-up phase of a prior investigational study may be enrolled if the investigator's judgment is that it will have no effect on safety, reactogenicity, or immunogenicity endpoints in this study, and that it does not violate the protocol requirements of the prior trial.

• Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.

• Presence of an axillary temperature >= 37.5°C, or acute symptoms greater than "mild" severity on the scheduled date of first vaccination. NOTE: The subject may be vaccinated at a later date, provided symptoms have resolved, vaccination occurs within the window specified by the protocol, and all other eligibility criteria continue to be satisfied.

• Diagnosed with cancer, or treatment for cancer, within the past 3 years.

• Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible.

• Persons with a history of histological-confirmed basal cell carcinoma of the skin successfully treated with local excisions only are excepted and may enroll within 3 years of diagnosis, but other histological types of skin cancer require a 3-year untreated and disease-free window as above.

• Women who are disease free 3 years or more after the treatment for breast cancer and receiving long-term prophylactic tamoxifen are excepted and may enroll.

• Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection.

• Clinically or virologically confirmed influenza infection within 6 months preceding the study start.

• Chronic administration of immunosuppressants or other immune modifying drugs within 6 months of study enrolment or planned administration during the study period.

• Receipt of any immunoglobulins and/or any blood products within 3 months of study enrolment or planned administration of any of these products during the study period.

• Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin outside of 24 hours prior to vaccination are eligible. Persons receiving prophylactic antiplatelet medications, e.g., low-dose aspirin, and without a clinically-apparent bleeding tendency, are eligible.

• An acute evolving neurological disorder or history of Guillain-Barré syndrome.

• Administration of any vaccines within 30 days before vaccination.

• Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine.

• Pregnant or lactating female

• Female planning to become pregnant or planning to discontinue contraceptive precautions.

• Any conditions which, in the opinion of the investigator, prevents the subjects from participating in the study.

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• GSK investigational vaccine GSK2340272A
Two intramuscular injections
• GSK investigational vaccine GSK2340269A
Two intramuscular injections

Locations

Country	Name	City	State
Belgium	GSK Investigational Site	Gent

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Belgium, 

References & Publications (1)

Roman F, Clément F, Dewé W, Walravens K, Maes C, Willekens J, De Boever F, Hanon E, Leroux-Roels G. Effect on cellular and humoral immune responses of the AS03 adjuvant system in an A/H1N1/2009 influenza virus vaccine administered to adults during two randomized controlled trials. Clin Vaccine Immunol. 2011 May;18(5):835-43. doi: 10.1128/CVI.00480-10. Epub 2011 Mar 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Seroconverted Subjects for Hemagglutination Inhibition (HI) Antibodies	Seroconversion was defined as: For initially seronegative subjects [antibody titer below (<) 1:10 prior to vaccination], antibody titer greater than or equal to (=) 1:40 after vaccination; For initially seropositive subjects (antibody titer = 1:10 prior to vaccination), antibody titer after vaccination = 4 fold the pre-vaccination antibody titer. The Flu strain assessed was A/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09).	At Day 42
Primary	Number of Seroprotected Subjects for HI Antibodies	A seroprotected subject was defined as a vaccinated subject with a serum hemagglutination inhibition (HI) titer = 1:40. The flu strain assessed was A/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09).	At Day 42
Primary	Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease	GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09.	At Day 42
Secondary	Number of Subjects With HI Antibody Concentrations Above the Cut-off Value	Seropositivity cut-off values assessed were equal to or above (=) 1:10 in the sera of subjects seronegative before vaccination. The Flu strain assessed was Flu A/CAL/7/09.	At Days 0, 21 and 42
Secondary	Number of Subjects With HI Antibody Concentrations Above the Cut-off Value	Seropositivity cut-off values assessed were equal to or above (=) 1:10 in the sera of subjects seronegative before vaccination. The Flu strain assessed was Flu A/CAL/7/09.	At Day 182
Secondary	Number of Subjects With HI Antibody Concentrations Above the Cut-off Value	Seropositivity cut-off values assessed were equal to or above (=) 1:10 in the sera of subjects seronegative before vaccination. The Flu strain assessed was Flu A/CAL/09.	At Day 364
Secondary	Titers for Serum HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease	Titers are presented as geometric mean titers (GMTs). The flu strain assessed was Flu A/CAL/7/09. The reference seropositivity cut-off value was = 1:10.	At Days 0, 21 and 42
Secondary	Titers for Serum HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease	Titers are presented as geometric mean titers (GMTs). The flu strain assessed was Flu A/CAL/7/09. The reference seropositivity cut-off value was = 1:10.	At Day 182
Secondary	Titers for Serum HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease	Titers are presented as geometric mean titers (GMTs). The flu strain assessed was Flu A/CAL/7/09. The reference seropositivity cut-off value was = 1:10.	At Day 364
Secondary	Number of Seroconverted Subjects for HI Antibodies	Seroconversion was defined as: For initially seronegative subjects (antibody titer < 1:10 prior to vaccination), antibody titer = 1:40 after vaccination; For initially seropositive subjects (antibody titer = 1:10 prior to vaccination), antibody titer after vaccination = 4 fold the pre-vaccination antibody titer. The Flu strain assessed was A/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09).	At Day 21
Secondary	Number of Seroconverted Subjects for HI Antibodies	Seroconversion was defined as: For initially seronegative subjects (antibody titer < 1:10 prior to vaccination), antibody titer = 1:40 after vaccination; For initially seropositive subjects (antibody titer = 1:10 prior to vaccination), antibody titer after vaccination = 4 fold the pre-vaccination antibody titer. The Flu strain assessed was A/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09).	At Day 42
Secondary	Number of Seroconverted Subjects for HI Antibodies	Seroconversion was defined as: For initially seronegative subjects (antibody titer < 1:10 prior to vaccination), antibody titer = 1:40 after vaccination; For initially seropositive subjects (antibody titer = 1:10 prior to vaccination), antibody titer after vaccination = 4 fold the pre-vaccination antibody titer. The Flu strain assessed was A/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09).	At Day 182
Secondary	Number of Seroconverted Subjects for HI Antibodies	Seroconversion was defined as: For initially seronegative subjects (antibody titer < 1:10 prior to vaccination), antibody titer = 1:40 after vaccination; For initially seropositive subjects (antibody titer = 1:10 prior to vaccination), antibody titer after vaccination = 4 fold the pre-vaccination antibody titer. The Flu strain assessed was A/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09).	At Day 364
Secondary	Number of Seroprotected Subjects for HI Antibodies	A seroprotected subject was defined as a vaccinated subject with a serum hemagglutination inhibition (HI) titer = 1:40. The flu strain assessed was A/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09).	At Days 0 and 21
Secondary	Number of Seroprotected Subjects for HI Antibodies	A seroprotected subject was defined as a vaccinated subject with a serum hemagglutination inhibition (HI) titer = 1:40. The flu strain assessed was A/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09).	At Day 42
Secondary	Number of Seroprotected Subjects for HI Antibodies	A seroprotected subject was defined as a vaccinated subject with a serum hemagglutination inhibition (HI) titer = 1:40. The flu strain assessed was A/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09).	At Day 182
Secondary	Number of Seroprotected Subjects for HI Antibodies	A seroprotected subject was defined as a vaccinated subject with a serum hemagglutination inhibition (HI) titer = 1:40. The flu strain assessed was A/California/7/2009 (H1N1)v-like influenza (Flu A/CAL/7/09).	At Day 364
Secondary	Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease	Seroconversion factor (SCF) was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09.	At Day 21
Secondary	Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease	Seroconversion factor (SCF) was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09.	At Day 42
Secondary	Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease	Seroconversion factor (SCF) was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09.	At Day 182
Secondary	Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease	Seroconversion factor (SCF) was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09.	At Day 364
Secondary	Titers for Serum Neutralizing Antibodies Against Flu A/Neth/602/09 Strain of Influenza Disease	Titers are presented as geometric mean titers (GMTs). The flu strain assessed was Flu A/Neth/602/09. The reference seropositivity cut-off value was = 1:8.	At Days 0, 21 and 42
Secondary	Number of Seroconverted Subjects for Serum Neutralizing Antibodies Against Flu A/Neth/602/09	Seroconversion was defined as: For initially seronegative subjects, antibody titer = 1:32 after vaccination; For initially seropositive subjects, antibody titer after vaccination = 4 fold the pre-vaccination antibody titer. The Flu strain assessed was Flu A/Neth/602/09.	At Days 21 and 42
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Secondary	Number of Days With Solicited Local Symptoms	The number of days with any solicited local symptoms reported during the solicited post-vaccination period. There were no subjects from GSK2340269A Group who reported Redness or Swelling.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Secondary	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were Fatigue, Headache, Joint pain at other location, Muscle aches, Shivering, Sweating and Fever [defined as axillary temperature equal to or above = 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = temperature > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Secondary	Number of Days With Solicited General Symptoms	The number of days with any solicited general symptoms reported during the solicited post-vaccination period. There were no subjects from GSK2340269A Group who reported Temperature.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Secondary	Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.	Within 21 days after the first vaccination and 63 days after the second vaccination (Day 0 - Day 20 and Day 21 - Day 83)
Secondary	Number of Subjects With Adverse Events of Specific Interest (AESIs)	An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.	During the entire study period (from Day 0 up to Day 364)
Secondary	Number of Subjects With Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	During the entire study period (from Day 0 up to Day 364)

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