Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Influenza Vaccines GSK2654911A and GSK2654909A Administered to Adults 18 to 64 Years of Age

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT01659086

Collaborator

(none)

422

Enrollment

Locations

Arms

18.9

Actual Duration (Months)

105.5

Patients Per Site

5.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of different formulations of a two-dose primary series and booster vaccination of monovalent Influenza H9N2 vaccine manufactured in Quebec, Canada with and without adjuvant, in adults 18 to 64 years of age.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: Investigational H9N2 vaccine GSK2654911A Biological: Investigational H9N2 vaccine GSK2654909A Biological: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

422 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

An Observer-blind Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Influenza Vaccines GSK2654911A and GSK2654909A Administered to Adults 18 to 64 Years of Age

Actual Study Start Date :

Aug 22, 2012

Actual Primary Completion Date :

Oct 26, 2012

Actual Study Completion Date :

Mar 19, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Subjects will receive the investigational vaccine GSK2654911A formulation 1 and placebo	Biological: Investigational H9N2 vaccine GSK2654911A 2 or 3 doses of GSK2654911A (different formulations) followed by 1 or 0 dose of saline placebo respectively, depending in the treatment group. All doses to be administered intramuscularly (IM) in deltoid region of arm. Biological: Placebo 1 dose of saline placebo administered intramuscularly (IM) in deltoid region of arm.
Experimental: Group B Subjects will receive the investigational vaccine GSK2654911A formulation 2 and placebo	Biological: Investigational H9N2 vaccine GSK2654911A 2 or 3 doses of GSK2654911A (different formulations) followed by 1 or 0 dose of saline placebo respectively, depending in the treatment group. All doses to be administered intramuscularly (IM) in deltoid region of arm. Biological: Placebo 1 dose of saline placebo administered intramuscularly (IM) in deltoid region of arm.
Experimental: Group C Subjects will receive the investigational vaccine GSK2654911A formulation 3 and placebo	Biological: Investigational H9N2 vaccine GSK2654911A 2 or 3 doses of GSK2654911A (different formulations) followed by 1 or 0 dose of saline placebo respectively, depending in the treatment group. All doses to be administered intramuscularly (IM) in deltoid region of arm. Biological: Placebo 1 dose of saline placebo administered intramuscularly (IM) in deltoid region of arm.
Experimental: Group D Subjects will receive the investigational vaccine GSK2654911A formulation 4 and placebo	Biological: Investigational H9N2 vaccine GSK2654911A 2 or 3 doses of GSK2654911A (different formulations) followed by 1 or 0 dose of saline placebo respectively, depending in the treatment group. All doses to be administered intramuscularly (IM) in deltoid region of arm. Biological: Placebo 1 dose of saline placebo administered intramuscularly (IM) in deltoid region of arm.
Experimental: Group E Subjects will receive the investigational vaccine GSK2654909A and placebo	Biological: Investigational H9N2 vaccine GSK2654909A 2 or 3 doses of GSK2654909A followed by 1 or 0 dose of saline placebo, respectively (treatment 5). All doses to be administered IM in deltoid region of arm. Biological: Placebo 1 dose of saline placebo administered intramuscularly (IM) in deltoid region of arm.
Experimental: Group F Subjects will receive the investigational vaccine GSK2654911A formulation 5	Biological: Investigational H9N2 vaccine GSK2654911A 2 or 3 doses of GSK2654911A (different formulations) followed by 1 or 0 dose of saline placebo respectively, depending in the treatment group. All doses to be administered intramuscularly (IM) in deltoid region of arm.
Experimental: Group G Subjects will receive the investigational vaccine GSK2654911A formulation 6	Biological: Investigational H9N2 vaccine GSK2654911A 2 or 3 doses of GSK2654911A (different formulations) followed by 1 or 0 dose of saline placebo respectively, depending in the treatment group. All doses to be administered intramuscularly (IM) in deltoid region of arm.
Experimental: Group H Subjects will receive the investigational vaccine GSK2654911A formulation 7	Biological: Investigational H9N2 vaccine GSK2654911A 2 or 3 doses of GSK2654911A (different formulations) followed by 1 or 0 dose of saline placebo respectively, depending in the treatment group. All doses to be administered intramuscularly (IM) in deltoid region of arm.
Experimental: Group I Subjects will receive the investigational vaccine GSK2654911A formulation 8	Biological: Investigational H9N2 vaccine GSK2654911A 2 or 3 doses of GSK2654911A (different formulations) followed by 1 or 0 dose of saline placebo respectively, depending in the treatment group. All doses to be administered intramuscularly (IM) in deltoid region of arm.
Experimental: Group J Subjects will receive the investigational vaccine GSK2654909A	Biological: Investigational H9N2 vaccine GSK2654909A 2 or 3 doses of GSK2654909A followed by 1 or 0 dose of saline placebo, respectively (treatment 5). All doses to be administered IM in deltoid region of arm.
Placebo Comparator: Placebo Group Subjects will receive Placebo	Biological: Placebo 1 dose of saline placebo administered intramuscularly (IM) in deltoid region of arm.

Outcome Measures

Primary Outcome Measures

Humoral immune response in terms of HI antibodies against H9N2 v-like antigen [Day 21]
Humoral immune response in terms of HI antibodies against H9N2 v-like antigen [Day 42]

Secondary Outcome Measures

Humoral immune response in terms of HI antibodies against H9N2 antigen [GMTs and seropositivity rates, SPR on Days 0, 7, 21, 28, 42, 182, 191, 385 and 546. SCR and MGI on Days 7, 21, 28, 42, 182, 191, 385 and 546. B-SCR and BF on Days 191, 385 and 546.]
Humoral immune response in terms of HI antibodies against H9N2 antigen for each vaccine group and for age strata (18-40 years; 41-64 years) [GMTs and seropositivity rates, SPR on Days 0, 7, 21, 28, 42, 182, 191, 385 and 546. SCR and MGI on Days 7, 21, 28, 42, 182, 191, 385 and 546. B-SCR and BF on Days 191, 385 and 546.]
Humoral immune response in terms of HI antibodies against any drift strain from H9N2 antigen or against any other H9 subtype antigen [GMTs and seropositivity rates on Days 0, 7, 21, 28, 42, 182 , 191, 385 and 546. SCR and MGI on Days 21, 42, 182, 191, 385, 546. SPR on Days 0, 21, 42, 182, 191, 385 and 546. B-SCR and BF on Days 191, 385 and 546.]
Humoral immune response in terms of neutralizing (MN) antibodies against H9N2 and against any drift strain (or other H9 subtype) [GMTs and seropositivity rate on Days 0, 21, 42, 182, 191, 385 and 546. VRR on Days 21, 42, 182, 191, 385, 546. Booster-VRR on Day 191, 385 and 546.]
Occurrence of local and general symptoms [During the 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after any vaccination]
Occurrence and relationship to vaccination of unsolicited adverse events [Within 21 days (Day 0 to Day 20, 21 to 41, 182 to 202) after any vaccination]
Occurrence and relationship to vaccination of adverse events with medically attended visits [During the entire study period (Day 0 - Day 546)]
Occurrence and relationship to vaccination of Adverse events of special interest (AESIs), potential Immune-Mediated Diseases (pIMDs), Serious Adverse Events (SAEs) and adverse pregnancy outcome [During the entire study period (Day 0 - Day 546)]
Number of subjects with clinical safety laboratory abnormalities [Days 0, 7, 21, 28, 42, 182, 191, and 385.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Male or female adults from 18 to 64 years of age (inclusive) at time of first study vaccination.
Written informed consent obtained from the subject.
Subjects who the investigator believes can and will comply with the requirements of the protocol.
Healthy subjects as established by medical history and physical examination.
Body weight of at least 110 lbs (49.9 kg).
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 they have practiced adequate contraception for 30 days prior to vaccination, and have a negative pregnancy test on the day of vaccination, and agree to continue to practice adequate contraception until 2 months after booster dose administration.

Exclusion Criteria:

Presence or evidence 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 or evidence of substance abuse.
Diagnosed with cancer, or treatment for cancer within three years.
Persons with a history of cancer who are disease-free without treatment for three years or more are eligible.
Persons with a history of histologically-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and may enroll, but other histologic types of skin cancer are exclusionary.
Women who are disease-free three years or more after treatment for breast cancer and receiving long-term prophylaxis may enroll.
Presence of a temperature ≥ 38.0ºC (≥100.4ºF), or acute symptoms greater than "mild" severity on the scheduled date of first vaccination.
Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection (no laboratory testing required).
Receipt of systemic glucocorticoids (e.g., prednisone ≥ 10 mg/day for more than 14 consecutive days) within 30 days prior to the first dose of study vaccine, or any other cytotoxic, immunosuppressive or immune-modifying drugs within 365 days of study enrollment. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed.
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 Guillain Barré Syndrome within 42 days of receipt of prior seasonal or pandemic influenza vaccine.
Administration of an inactive vaccine within 14 days or of a live attenuated vaccine within 30 days before the first dose of study vaccine/product.
Planned administration of any vaccine other than the study vaccine/product before blood sampling at the Day 42 visit.
Previous administration of any H9 vaccine or physician-confirmed H9 disease.
Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Receipt of any immunoglobulins and/or any blood products within 90 days before study enrolment or planned administration of any of these products during the study period.
Any known or suspected allergy to any constituent of influenza vaccines or component used in the manufacturing process of the study vaccine including a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
Known pregnancy or a positive urine beta-human chorionic gonadotropin (β-hCG) test result before the first vaccination.
Lactating or nursing women.
Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Miami	Florida	United States	33143
2	GSK Investigational Site	Edison	New Jersey	United States	08817
3	GSK Investigational Site	Austin	Texas	United States	78705
4	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1H 2G2