Clinical trial NCT01659086: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Keywords: Influenza
Immunogenicity
H9N2
Safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-08-07
Enrollment: 422
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Humoral immune response in terms of HI antibodies against H9N2 v-like antigen
timeFrame: Day 21
measure: Humoral immune response in terms of HI antibodies against H9N2 v-like antigen
timeFrame: Day 42
Secondary outcomes:
measure: Humoral immune response in terms of HI antibodies against H9N2 antigen
timeFrame: 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.
measure: 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)
timeFrame: 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.
measure: Humoral immune response in terms of HI antibodies against any drift strain from H9N2 antigen or against any other H9 subtype antigen
timeFrame: 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.
measure: Humoral immune response in terms of neutralizing (MN) antibodies against H9N2 and against any drift strain (or other H9 subtype)
timeFrame: 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.
measure: Occurrence of local and general symptoms
timeFrame: During the 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after any vaccination
measure: Occurrence and relationship to vaccination of unsolicited adverse events
timeFrame: Within 21 days (Day 0 to Day 20, 21 to 41, 182 to 202) after any vaccination
measure: Occurrence and relationship to vaccination of adverse events with medically attended visits
timeFrame: During the entire study period (Day 0 - Day 546)
measure: 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
timeFrame: During the entire study period (Day 0 - Day 546)
measure: Number of subjects with clinical safety laboratory abnormalities
timeFrame: Days 0, 7, 21, 28, 42, 182, 191, and 385.
Other outcomes:
Locations:
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Edison
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Madan A, Collins H, Sheldon E, Frenette L, Chu L, Friel D, Drame M, Vaughn DW, Innis BL, Schuind A. Evaluation of a primary course of H9N2 vaccine with or without AS03 adjuvant in adults: A phase I/II randomized trial. Vaccine. 2017 Aug 16;35(35 Pt B):4621-4628. doi: 10.1016/j.vaccine.2017.07.013. Epub 2017 Jul 15.