Study to Evaluate GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Human Immunodeficiency Virus (HIV)-Infected Subjects

NCT01165203 | Completed Phase 2 Results

• 1 other identifier: 112673
• Study Type: interventional
• Target: 123
• Locations: 3 countries
• Sites: 15

Brief Summary

This observer-blind study will evaluate the safety and immunogenicity of GlaxoSmithKline (GSK) Biologicals' investigational Herpes Zoster (HZ) vaccine GSK1437173A in Human Immunodeficiency Virus (HIV) infected subjects, firstly enrolling subjects treated with antiretroviral therapy (ART) and with high CD4 T cell counts, and subsequently ART-treated subjects with low CD4 T cell counts, and ART-naïve subjects with high CD4 T cell counts. This Protocol Posting has been updated following Amendment 1 of the Protocol, August 2010. The impacted sections is exclusion criteria.

Conditions

Herpes Zoster

Keywords

immunogenicity; vaccine; safety; HIV; Herpes Zoster

Outcome Measures

Primary Outcomes (21)

• Number of Subjects With Serious Adverse Events (SAEs)

  Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  From Month 0 to Month 18

• Number of Subjects With SAEs Related to Study Participation or to a Concurrent GSK Medication/Vaccine

  Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  From screening (up to 21 days prior to Month 0) until Month 18

• Number of Subjects With Any Fatal SAEs

  Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  From screening (up to 21 days prior to Month 0) until Month 18

• Number of Subjects With Any Adverse Events (AEs) of Specific Interest

  AEs of specific interest include new onset of autoimmune diseases (NOADs) and other immune mediated inflammatory disorders from administration of the first dose of vaccine/placebo.

  From Month 0 until Month 18

• Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms

  Assessed solicited local symptoms were pain, redness and swelling. Any = incidence of a particular symptom regardless of their intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

  Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses

• Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

  Assessed solicited general symptoms were fatigue, gastrointestinal (symptoms included nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia, shivering and temperature \[defined as oral/axillary temperature above (\>) 37.5 degrees Celsius (°C)\]. Any = incidence of a particular symptom regardless of their intensity grade or relationship to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

  Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses

• Number of Subjects With Unsolicited AEs

  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.

  Within 30 days (Days 0-29) after each vaccination

• Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges

  The assessed parameters were Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Basophils, Bilirubin Total, Bilirubin Conjugated / Direct, Creatinine, Eosinophils, Glucose, Bicarbonate, Haemoglobin, Potassium, Lymphocytes, Monocytes, Sodium, Neutrophils, Platelets and White Blood Cells. Tabulation was made by relation to the normal laboratory ranges: below, within or above, and also status unknown.

  At Screening Visit (up to 21 days prior to Month 0)

• Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges

  The assessed parameters were Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Basophils, Bilirubin Total, Bilirubin Conjugated / Direct, Creatinine, Eosinophils, Glucose, Bicarbonate, Haemoglobin, Potassium, Lymphocytes, Monocytes, Sodium, Neutrophils, Platelets and White Blood Cells. Tabulation was made by relation to the normal laboratory ranges: below, within or above, and also status unknown.

  At Month 1

• Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges

  The assessed parameters were Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Basophils, Bilirubin Total, Bilirubin Conjugated / Direct, Creatinine, Eosinophils, Glucose, Bicarbonate, Haemoglobin, Potassium, Lymphocytes, Monocytes, Sodium, Neutrophils, Platelets and White Blood Cells. Tabulation was made by relation to the normal laboratory ranges: below, within or above, and also status unknown.

  At Month 2

• Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges

  The assessed parameters were Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Basophils, Bilirubin Total, Bilirubin Conjugated / Direct, Creatinine, Eosinophils, Glucose, Bicarbonate, Haemoglobin, Potassium, Lymphocytes, Monocytes, Sodium, Neutrophils, Platelets and White Blood Cells. Tabulation was made by relation to the normal laboratory ranges: below, within or above, and also staus unknown.

  At Month 3

• Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges

  The assessed parameters were Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Basophils, Bilirubin Total, Bilirubin Conjugated / Direct, Creatinine, Eosinophils, Glucose, Bicarbonate, Haemoglobin, Potassium, Lymphocytes, Monocytes, Sodium, Neutrophils, Platelets and White Blood Cells. Tabulation was made by relation to the normal laboratory ranges: below, within or above, and also status unknown.

  At Month 6

• Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges

  The assessed parameters were Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Basophils, Bilirubin Total, Bilirubin Conjugated / Direct, Creatinine, Eosinophils, Glucose, Bicarbonate, Haemoglobin, Potassium, Lymphocytes, Monocytes, Sodium, Neutrophils, Platelets and White Blood Cells. Tabulation was made by relation to the normal laboratory ranges: below, within or above, and also staus unknown.

  At Month 7

• Number of Subjects With Any Significant Change in Antiretroviral Therapy (ART), Including Initiation of ART in ART-naïve Subjects

  In this analysis, results were tabulated for the main study groups. Significant changes to ART appeared due to failure to control HIV viral load and due to failure to maintain high CD4 cells count.

  From Month 0 until Month 18

• Number of Subjects With Any AIDS-defining Condition

  In this analysis, results were tabulated for the main study groups.

  From Month 0 until Month 18

• Number of Subjects With Any Pre-defined Changes in HIV Viral Load (VL) and CD4 T-cell Count

  In this analysis, results were tabulated for the main study groups.

  From Month 1 to Month 7

• Number of Subjects With Any Significant Change in Antiretroviral Therapy (ART), Including Initiation of ART in ART-naïve Subjects, by HIV Status

  In this analysis, results were tabulated by HIV status

  From Month 0 to Month 18

• Number of Subjects With Any AIDS-defining Condition, by HIV Status

  In this analysis, results were tabulated by HIV status

  From Month 0 to Month 18

• Number of Subjects With Any Pre-defined Changes in HIV Viral Load (VL) and CD4 T-cell Count, by HIV Status

  In this analysis, results were tabulated by HIV status.

  From Month 1 to Month 7

• Frequency of gE-specific CD4 T-cells

  The analysis focused on CD4 T-cells expressing at least 2 cytokines (among interferon-gamma (IFN-g) , interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-a) and/or CD40 ligand (CD40L)) as determined by in vitro intracellular cytokine staining (ICS) at Month 7 in ART and non-ART cohorts presenting high CD4 counts at enrollment.

  At Month 7

• -Anti-gE Antibody (Ab) Concentrations

  -Anti-gE antibody (Ab) concentrations were determined by Enzyme-Linked Immunosorbent Assay (ELISA) at Month 7 in ART and non-ART cohorts presenting high CD4 counts at enrolment. Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).

  At Month 7

Secondary Outcomes (7)

• -Frequencies of Varicella-Zoster Virus (VZV)- and gE-specific CD4 T-cells

  At Month 0, 1, 2, 3, 6, 7 and 18

• -Frequencies of Varicella-Zoster Virus (VZV)- and gE-specific CD4 T-cells, by HIV Status

  At Months 0, 1, 2, 3, 6, 7 and 18

• -Anti-VZV and Anti-gE Antibody Concentrations

  At Months 0, 1, 2, 3, 6, 7 and 18

• -Anti-VZV and Anti-gE Antibody Concentrations, by HIV Status

  At Months 0, 1, 2, 3, 6, 7 and 18

• Number of Subjects With Any Herpes Zoster (HZ) Cases and Complications

  From Month 0 until Month 18

Study Arms (2)

GSK1437173A Group

EXPERIMENTAL

Subjects who received three doses of GSK1437173A vaccine (Months 0, 2 and 6), administered intramuscularly, in the deltoid muscle of the non-dominant arm.

Biological: Herpes Zoster Vaccine GSK1437173A

Placebo Group

PLACEBO COMPARATOR

Subjects who received three doses of placebo (Months 0, 2 and 6), administered intramuscularly, in the deltoid muscle of the non-dominant arm.

Biological: Placebo

Interventions

Herpes Zoster Vaccine GSK1437173A BIOLOGICAL

intramuscular injection

Also known as: HZ/su vaccine

GSK1437173A Group

Placebo BIOLOGICAL

intramuscular injection

Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol;
• Male and female subjects at least 18 years old at the time of vaccination;
• Subjects born before 1985 and not from a tropical region. Subjects born in 1985 or later and subjects born before 1985 in tropical regions must have a history of Varicella Zoster virus (VZV) infection or serological evidence of prior VZV infection;
• Written informed consent obtained from the subject;
• 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.
• OR 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;
• Known to be human immunodeficiency virus-1 (HIV-1) infected, diagnosed at least 1 year prior to enrolment;
• For the antiretroviral therapyART High CD4 and ART Low CD4 cohorts:
• Stable on ART for at least one year
• CD4 T cell count \>= 50 cells /mm3 at screening
• Undetectable VL at screening;
• For the non-ART High CD4 cohort:
• ART-naïve subjects who have never received anti-retroviral therapy after HIV diagnosis and for whom commencement of ART is not expected based on current assessment within next seven months;
• HIV VL \>= 1000 copies/mL and \<= 100 000 copies/mL at screening
• CD4 T cell count \>= 500 cells/mm3 at screening.

You may not qualify if:

• 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;
• Vaccination against varicella or herpes zoster (HZ) within the previous 12 months;
• Occurrence of a varicella or HZ episode within the previous 12 months;
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Additionally, consider allergic reactions to other material or equipment related to study participation. Please note, the vaccine and vials in this study do not contain latex;
• Has currently an Acquired Immunodeficiency Syndrome (AIDS) defining condition;
• Opportunistic infection or AIDS-associated malignancy in the previous year;
• Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease other than HIV infection or immunosuppressive/cytotoxic therapy;
• Administration of immunoglobulins, and/or any blood products within 90 days preceding the first dose of study vaccine/placebo or planned administration during the study period;
• Chronic administration of immunosuppressive or other immune-modifying drugs within 6 months prior to the first vaccine dose;
• Administration and/or planned administration of a vaccine not foreseen by the study protocol within 30 days before dose 1, dose 2 and/or 3 of vaccine and/or within 30 days after any dose. However, licensed non-replicating vaccines may be administered up to 8 days prior to dose 1, 2 and/or 3, and/or at least 14 days after any dose of study vaccine;
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product;
• Acute disease at the time of enrolment;
• Any contraindication to receiving intramuscular injections;
• Any condition or illness which might interfere with the evaluation of the safety or immunogenicity of the vaccine;
• Active hepatitis B (HBV) infection or active hepatitis C (HCV) infection.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Long Beach, California, 90813, United States

Location

GSK Investigational Site

San Francisco, California, 94115, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Santa Fe, New Mexico, 87505, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44791, Germany

Location

GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, 40237, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Berlin, 13353, Germany

Location

GSK Investigational Site

Hamburg, 20146, Germany

Location

GSK Investigational Site

Woolwich, London, London, SE18 4QH, United Kingdom

Location

GSK Investigational Site

London, E1 1BB, United Kingdom

Location

GSK Investigational Site

London, NW3 2QG, United Kingdom

Location

GSK Investigational Site

London, SW10 9TH, United Kingdom

Location

Related Publications (1)

• Berkowitz EM, Moyle G, Stellbrink HJ, Schurmann D, Kegg S, Stoll M, El Idrissi M, Oostvogels L, Heineman TC; Zoster-015 HZ/su Study Group. Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomized, placebo-controlled study. J Infect Dis. 2015 Apr 15;211(8):1279-87. doi: 10.1093/infdis/jiu606. Epub 2014 Nov 3.

  PMID: 25371534 DERIVED

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

Herpes Zoster

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; 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 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 19, 2010
• Study Start: September 30, 2010
• Primary Completion: July 6, 2012
• Study Completion: May 14, 2013
• Last Updated: April 30, 2018
• Results First Posted: June 7, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

DE (6); US (5); GB (4)