Evaluation of Non-typable Haemophilus Influenzae and Pneumococcal Protein Vaccine Formulations in Young Adults

NCT00814489 | Completed Phase 1 Results

• 1 other identifier: 112076
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, reactogenicity and immunogenicity of 2 formulations of a non-typable Haemophilus influenzae and pneumococcal candidate vaccine in young adults. Subjects will be vaccinated 2 times in an observer-blind manner with an interval of 2 months. The subjects receiving Engerix-B will receive in an open-manner a third dose of the vaccine at Month 6. The protocol posting has been updated following a protocol amendment.

Conditions

Streptococcus Pneumoniae; Haemophilus Influenzae

Keywords

Non-typable Haemophilus influenzae; protein vaccine; Streptococcus pneumoniae; young adults

Outcome Measures

Primary Outcomes (6)

• Number of Subjects With Any Solicited Local and General Symptoms

  Solicited local symptoms assessed were pain, redness and swelling. Any solicited local symptom was defined as occurrence of any solicited local symptom regardless of intensity grade. Solicited general symptoms assessed were fatigue, gastrointestinal, headache, malaise, myalgia and temperature Any temperature was defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C). For other symptoms: Any = any general symptom reported irrespective of intensity grade and relationship to vaccination.

  During a 7-day follow up period after any vaccination

• Number of Subjects With Any Unsolicited Adverse Events (AE)

  An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.

  During a 30-day (Days 0-29) follow up period after any vaccination

• Number of Subjects With Any Serious Adverse Events (SAEs)

  SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination.

  From Day 0 to Day 420

• Number of Subjects With Any Biochemical Laboratory Abnormalities

  Biochemical parameters assessed in blood samples include alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA) and urea (URE). Abnormalities reported include values outside the normal ranges. Time points were presented as before (Pre) or after (Post) Dose 1, 2 or 3.

  During a 7-day follow up period after vaccine dose 1 and 2 and at Days 180, 300 and 420

• Number of Subjects With Any Hematological Laboratory Abnormalities

  Hematological parameters assessed in blood samples include red blood cells (RBC), white blood cells (WBC - including Basophils (BAS), neutrophils (NEU), lymphocytes (LYM), eosinophils (EOS) and monocytes (MON), blood platelets (PLA) and Hemoglobin (HEM). Abnormalities reported include values outside the normal ranges. This outcome presents results for RBC, WBC High and Low, PLA and HEM. Time points were presented as before (pre) or after (post) doses 1, 2 or 3.

  During a 7-day follow up period after vaccine dose 1 and 2 and at Days 180, 300 and 420.

• Number of Subjects With Any Hematological Laboratory Abnormalities

  Hematological parameters assessed in blood samples include red blood cells (RBC), white blood cells (WBC - including Basophils (BAS), neutrophils (NEU), lymphocytes (LYM), eosinophils (EOS) and monocytes (MON)), blood platelets (PLA) and Hemoglobin (HEM). Abnormalities reported include values outside the normal ranges. This outcome presents results for BAS, NEU, LYM, EOS and MON. Time points were presented as before (Pre) or after (Post) Dose 1, 2 or 3.

  During a 7-day follow up period after vaccine dose 1 and 2 and at Days 180, 300 and 420.

Secondary Outcomes (3)

• Concentrations of Antibodies Against Protein D (Anti-PD), Pneumolysin (Anti-Ply) and Pneumococcal Histidine Triad D (Anti-PhtD)

  Days 0, 30, 60, 90, 180 and 420.

• Mean Number of Influenza-specific Cluster of Differentiation (CD) 4 T-cells.

  Prior to first vaccination (Day 0), at 14 days post vaccination 1 (Day 14) and 2 (Day 74) and at Day 480.

• Mean Number of Influenza-specific Cluster of Differentiation (CD) 8 T-cells.

  Prior to first vaccination (Day 0), at 14 days post vaccination 1 (Day 14) and 2 (Day 74) and at Day 480.

Study Arms (3)

GSK2254233A Group

EXPERIMENTAL

Subjects received 2 doses of adjuvanted Non-Typable Haemophilus influenza and pneumococcal vaccine GSK2254233A at Months 0 and 2. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.

Biological: GSK2231395A

GSK2254232A Group

EXPERIMENTAL

Subjects received 2 doses of non-adjuvanted Non-Typable Haemophilus influenza and pneumococcal vaccine GSK2254232A at Months 0 and 2. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.

Biological: GSK2231395A

Engerix Group

ACTIVE COMPARATOR

Subjects received 3 doses of Engerix vaccine at Months 0, 2 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.

Biological: Engerix-B

Interventions

GSK2231395A BIOLOGICAL

Two doses will be administered intramuscularly; one dose at Month 0 and the second dose a Month 2. Two different formulations of this vaccine will be tested.

GSK2254232A Group; GSK2254233A Group

Engerix-B BIOLOGICAL

Two doses will be administered intramuscularly; one dose at Month 0 and the second dose a Month 2.

Engerix Group

Eligibility Criteria

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

You may qualify if:

• Subjects who the investigator believes will comply with the requirements of the protocol should be enrolled in the study.
• A male or female between, and including, 18 and 40 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject.
• Subject without medical history, clinical finding or laboratory finding, which, in the opinion of the investigator, could pose a safety concern or interfere with the protocol.
• If the subject is female, and of childbearing potential, she agrees to use adequate contraception and not become pregnant for the duration of the study.

You may not qualify if:

• Pneumonia within 3 years prior to 1st vaccination.
• Invasive Pneumococcal Disease within 3 years prior to 1st vaccination.
• Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period or participation to another pharmaceutical/vaccine study.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccines, with the exception of the influenza vaccine which can be administered \>14 days prior to or \>14 days following vaccine doses 1 and 2.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus infection.
• History of reaction or hypersensitivity to any component of the vaccine.
• Any serious, uncontrolled disease likely to interfere with the study as determined by history, physical examination or laboratory screening, as per the judgment of the Investigator.
• Inflammatory processes such as known chronic infections.
• All past or current malignancies and lymphoproliferative disorders.
• Laboratory evidence of haematological and biochemical abnormalities.
• Acute disease at the time of enrolment/vaccination.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Karlskrona, SE-371 41, Sweden

Location

Related Publications (1)

• Berglund J, Vink P, Tavares Da Silva F, Lestrate P, Boutriau D. Safety, immunogenicity, and antibody persistence following an investigational Streptococcus pneumoniae and Haemophilus influenzae triple-protein vaccine in a phase 1 randomized controlled study in healthy adults. Clin Vaccine Immunol. 2014 Jan;21(1):56-65. doi: 10.1128/CVI.00430-13. Epub 2013 Oct 30.

  PMID: 24173029 DERIVED

MeSH Terms

Conditions

Haemophilus Infections

Interventions

Engerix-B

Condition Hierarchy (Ancestors)

Pasteurellaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

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: December 23, 2008
• First Posted: December 25, 2008
• Study Start: January 8, 2009
• Primary Completion: May 4, 2009
• Study Completion: June 10, 2010
• Last Updated: August 8, 2018
• Results First Posted: January 25, 2013

Record last verified: 2013-07

Locations

SE (1)