Safety and Immune Response of Candidate H1N1 Influenza Vaccine GSK2340274A Following Seasonal Influenza Vaccination in Adults

NCT01059617 | Completed Phase 1 Results

• 1 other identifier: 113483
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 3

Brief Summary

This study is designed to characterize the safety and immunogenicity of a' pandemic influenza (H1N1) candidate vaccine GSK2340274A in adults 19 to 40 years who have never received influenza vaccination.

Conditions

Influenza

Keywords

Pandemic; GSK Bio's influenza vaccine GSK2340274A; H1N1; Influenza

Outcome Measures

Primary Outcomes (12)

• Number of Seroconverted Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

  Seroconversion rate (SCR) was defined as the number of subjects who have either a pre-vaccination reciprocal HI titer \< 10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus.

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

• Number of Seroprotected Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

  Seroprotection rate (SPR) was defined as the number of subjects with H1N1 reciprocal HI titers ≥ 40 against the tested vaccine virus.

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

• Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

  Geometric mean fold-rise (GMFR), or seronversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus.

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 122 to Day 164).

• Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

  A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cut-off value of 1:10.

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

• Titers for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

  Titers were expressed as geometric mean antibody titers (GMTs).

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

• Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Titers Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

  VRR for microneutralization titers was defined as the incidence rate of vaccinees with at least a 4-fold increase in post vaccination reciprocal titer relative to Day 0. The cut-off value for microneutralization titers is 1:28.

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

• Number of Seroconverted Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

  Seroconversion rate (SCR) was defined as the number of subjects who have either a pre-vaccination reciprocal HI titer \< 1:10 and a post-vaccination reciprocal titer ≥ 1:40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus.

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

• Number of Seroprotected Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

  Seroprotection rate (SPR) was defined as the number of subjects with H1N1 reciprocal HI titers ≥ 1:40 against the tested vaccine virus.

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

• Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

  Geometric mean fold-rise (GMFR), or seronversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus.

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 122 to Day 164).

• Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

  A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cut-off value of 1:10.

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

• Titers for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

  Titers were expressed as geometric mean antibody titers (GMTs).

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

• Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Titers Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

  VRR for microneutralization titers was defined as the incidence rate of vaccinees with at least a 4-fold increase in post vaccination reciprocal titer relative to Day 0. The cut-off value for microneutralization titers is 1:28.

  21 days following the second dose of Arepanrix or the unadjuvanted formulation of Arepanrix vaccines (At Day 164).

Secondary Outcomes (32)

• Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

  At Day 122 and Day 304

• Titers for Hemagglutination Inhibition (HI) Antibodies Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

  At Days 122 and 304

• Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Titers Against A/California/7/2009 (H1N1)V-like Virus-homologous Vaccine Strain.

  Entire study period up to Day 507

• Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

  At Days 0 and 304

• Titers for Hemagglutination Inhibition (HI) Antibodies Against A/Brisbane/59/2007 (H1N1) Virus-heterologous Vaccine Strain.

  At Day 0 and Day 304

Study Arms (4)

Flulaval/Arepanrix Group

EXPERIMENTAL

subjects received Flulaval vaccine on Day 0 and Arepanrix vaccine on Day 122 and Day 143. All vaccines were given intramuscularly, in the deltoid region of the non-dominant arm at Days 0 and 122 and of the dominant arm at Day 143.

Biological: GSK Biologicals' FluLaval®; Biological: GSK Biologicals' investigational H1N1 Influenza Vaccine - GSK2340274A

Flulaval/Unadjuvanted Arepanrix Group

EXPERIMENTAL

subjects received Flulaval vaccine on Day 0 and the unadjuvanted formulation of Arepanrix vaccine on Day 122 and Day 143. All vaccines were given intramuscularly, in the deltoid region of the non-dominant arm at Days 0 and 122 and of the dominant arm at Day 143.

Biological: GSK Biologicals' FluLaval®; Biological: GSK Biologicals' investigational H1N1 Influenza Vaccine - GSK2340273A

Placebo/Arepanrix Group

EXPERIMENTAL

subjects received a saline placebo on Day 0 and Arepanrix vaccine on Day 122 and Day 143. All vaccines were given intramuscularly, in the deltoid region of the non-dominant arm at Days 0 and 122 and of the dominant arm at Day 143.

Biological: Placebo (saline); Biological: GSK Biologicals' investigational H1N1 Influenza Vaccine - GSK2340274A

Placebo/Unadjuvanted Arepanrix Group

EXPERIMENTAL

subjects received a saline placebo on Day 0 and the unadjuvanted formulation of Arepanrix vaccine on Day 122 and Day 143. All vaccines were given intramuscularly, in the deltoid region of the non-dominant arm at Days 0 and 122 and of the dominant arm at Day 143.

Biological: Placebo (saline); Biological: GSK Biologicals' investigational H1N1 Influenza Vaccine - GSK2340273A

Interventions

GSK Biologicals' FluLaval® BIOLOGICAL

Intramuscular injection

Flulaval/Arepanrix Group; Flulaval/Unadjuvanted Arepanrix Group

Placebo (saline) BIOLOGICAL

Intramuscular injection

Placebo/Arepanrix Group; Placebo/Unadjuvanted Arepanrix Group

GSK Biologicals' investigational H1N1 Influenza Vaccine - GSK2340274A BIOLOGICAL

Intramuscular injections

Flulaval/Arepanrix Group; Placebo/Arepanrix Group

GSK Biologicals' investigational H1N1 Influenza Vaccine - GSK2340273A BIOLOGICAL

Intramuscular injections

Flulaval/Unadjuvanted Arepanrix Group; Placebo/Unadjuvanted Arepanrix Group

Eligibility Criteria

• Age: 19 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who the investigator believes can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).
• Written informed consent obtained from the subject.
• Male or female adults, 19-40 years of age at the time of the first vaccination.
• Body weight of at least 110 pounds (49.9 kg).
• Safety laboratory tests results within the parameters specified by protocol.
• Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits as documented by signature on the informed consent document.
• 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 other multiple-user device (i.e., a common-use phone serving multiple rooms or apartments).
• Female subjects of non-childbearing potential may be enrolled in the study.
• Non-childbearing potential is defined as 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

You may not qualify if:

• Previous vaccination with an A/California/7/2009 (H1N1)v-like virus vaccine
• A medical history of physician-confirmed infection with an A/California/7/2009 (H1N1)v-like virus.
• Prior receipt at any time of any seasonal influenza vaccine.
• Planned administration of any vaccine not foreseen by the study protocol (including any influenza vaccine other than the study vaccine) between Days 0 and the Day 164 phlebotomy.
• Administration of any licensed vaccine within 30 days before the first study vaccine dose.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Receipt of systemic glucocorticoids (e.g., prednisone ≥ 0.5 mg/kg/day, or ≥ 10 mg/day \[whichever is less\] for more than 14 consecutive days) within one month prior to study enrolment, or any other cytotoxic or immunosuppressive drug within six months of study enrolment. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed.
• Receipt of any immunoglobulins and/or any blood products within 9 months of study enrolment or planned administration of any of these products during the study period.
• Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
• History of anemia.
• Presence of a temperature ≥ 38.0ºC (≥100.4ºF), (oral temperature assessment preferred), or acute symptoms greater than "mild" severity on the scheduled date of first vaccination
• Diagnosed with cancer, or treatment for cancer, within 3 years.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. (No laboratory testing is required.)
• 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 acetylsalicylic acid, and without a clinically-apparent bleeding tendency, are eligible.
• An acute evolving neurological disorder or history of Guillain-Barré syndrome within six weeks of receipt of any vaccine.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Milford, Massachusetts, 01757, United States

Location

GSK Investigational Site

Salisbury, North Carolina, 28144, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

Related Links

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

MeSH Terms

Conditions

Influenza, Human

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: February 1, 2010
• Study Start: February 9, 2010
• Primary Completion: January 14, 2011
• Study Completion: October 21, 2011
• Last Updated: August 20, 2018
• Results First Posted: June 7, 2012

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share

Locations

US (3)