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

• ClinicalTrials.gov Identifier: NCT00951041
• Recruitment Status: Completed
• First Posted: August 4, 2009
• Results First Posted: November 26, 2018
• Last Update Posted: November 26, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: GSK investigational vaccine GSK2340272A; Biological: GSK investigational vaccine GSK2340269A	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity Study of GSK Biologicals' Influenza Vaccine GSK2340272A in Adults Aged 18 to 60 Years
• Actual Study Start Date: August 11, 2009
• Actual Primary Completion Date: August 30, 2010
• Actual Study Completion Date: August 30, 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: GSK2340272A Group; Healthy male or female adults, between and including 18 to 60 years of age, who received two doses of GSK2340272A vaccine. The first vaccine dose was administered intramuscularly in the deltoid region of the non-dominant arm at Day 0, and the second vaccine dose was administered intramuscularly in the deltoid region of the dominant arm at Day 21.	Biological: GSK investigational vaccine GSK2340272A; Two intramuscular injections
Experimental: GSK2340269A Group; Healthy male or female adults, between and including 18 to 60 years of age, who received two doses of GSK2340269A vaccine. The first vaccine dose was administered intramuscularly in the deltoid region of the non-dominant arm at Day 0, and the second vaccine dose was administered intramuscularly in the deltoid region of the dominant arm at Day 21.	Biological: GSK investigational vaccine GSK2340269A; Two intramuscular injections

Outcome Measures

Primary Outcome Measures :

1. Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease [ Time Frame: At Day 35 ]
   Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old. The primary endpoint results consist in those presented for GSK2340272A Group.
2. Number of Seroconverted Subjects for HI Antibodies [ Time Frame: At Day 35 ]
   Seroconversion (SCR) was defined as follows: for initially seronegative subjects, antibody titer equal to or above (≥) 1:40 after vaccination; for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old. The primary endpoint results consist in those presented for GSK2340272A Group.
3. Number of Seroprotected Subjects for HI Antibodies [ Time Frame: At Day 35 ]
   A seroprotected subject was defined as a vaccinated subject with a serum HI titer equal to or above (≥) 1:40. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old. The primary endpoint results consist in those presented for GSK2340272A Group.
4. Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease [ Time Frame: At Day 35 ]
   GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old. The primary endpoint results consist in those presented for GSK2340272A Group.

Secondary Outcome Measures :

1. Titers for Serum HI Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease [ Time Frame: At Days 0 and 21 ]
   Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
2. Titers for Serum HI Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease [ Time Frame: At Day 182 ]
   Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
3. Titers for Serum HI Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease [ Time Frame: At Day 364 ]
   Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
4. Number of Seroconverted Subjects for HI Antibodies [ Time Frame: At Day 21 ]
   Seroconversion (SCR) was defined as follows: for initially seronegative subjects, antibody titer equal to or above (≥) 1:40 after vaccination; for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
5. Number of Seroconverted Subjects for HI Antibodies [ Time Frame: At Day 182 ]
   Seroconversion (SCR) was defined as follows: for initially seronegative subjects, antibody titer equal to or above (≥) 1:40 after vaccination; for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
6. Number of Seroconverted Subjects for HI Antibodies [ Time Frame: At Day 364 ]
   Seroconversion (SCR) was defined as follows: for initially seronegative subjects, antibody titer equal to or above (≥) 1:40 after vaccination; for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
7. Number of Seroprotected Subjects for HI Antibodies [ Time Frame: At Days 0 and 21 ]
   A seroprotected subject was defined as a vaccinated subject with a serum HI titer equal to or above (≥) 1:40. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
8. Number of Seroprotected Subjects for HI Antibodies [ Time Frame: At Day 182 ]
   A seroprotected subject was defined as a vaccinated subject with a serum HI titer equal to or above (≥) 1:40. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
9. Number of Seroprotected Subjects for HI Antibodies [ Time Frame: At Day 364 ]
   A seroprotected subject was defined as a vaccinated subject with a serum HI titer equal to or above (≥) 1:40. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
10. Seroconversion Factor (SCF) for HI Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease [ Time Frame: At Day 21 ]
    SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
11. SCF for HI Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease [ Time Frame: At Day 35 ]
    SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
12. SCF for HI Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease [ Time Frame: At Day 182 ]
    SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
13. SCF for HI Antibodies Against Flu A/California/7/2009 Strain of Influenza Disease [ Time Frame: At Day 364 ]
    SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/California/7/2009 (H1N1)v-like, in subjects 18-60 years old.
14. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) follow-up period after each dose and across doses ]
    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.
15. Number of Days With Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) follow-up period after each dose and overall ]
    The number of days with any solicited local symptoms reported during the solicited post-vaccination period.
16. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) follow-up period after each dose and across doses ]
    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 and relationship to vaccination. Grade 3 symptom = symptom that prevented normal everyday activities. Grade 3 fever = fever above (>) 40.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
17. Number of Days With Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) follow-up period after each dose and overall ]
    The number of days with any solicited general symptoms reported during the solicited post-vaccination period.
18. Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: During the 21-day (Days 0-20) follow-up after the first vaccination and during the 63-day (Days 21-83) follow-up after the second vaccination (From Day 0 to Day 84) ]
    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.
19. Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (From Day 0 up to Day 364) ]
    SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
20. Number of Subjects With Adverse Events of Specific Interest (AESI) [ Time Frame: During the entire study period (From Day 0 up to Day 364) ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.
• 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 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.

Contacts and Locations

Locations

Germany

GSK Investigational Site

Dresden, Sachsen, Germany, 01097

GSK Investigational Site

Dresden, Sachsen, Germany, 01099

GSK Investigational Site

Dresden, Sachsen, Germany, 01307

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. 

Study Data/Documents: Study Protocol 

Identifier: 113574
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 113574
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 113574
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 113574
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 113574
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 113574
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 113574
For additional information about this study please refer to the GSK Clinical Study Register

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00951041
• Other Study ID Numbers: 113574
• First Posted: August 4, 2009
• Results First Posted: November 26, 2018
• Last Update Posted: November 26, 2018
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:

influenza infection; GSK Bio's influenza vaccine GSK2340272A

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs