Clinical trial NCT01165203: Study to Evaluate GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Human Immunodeficiency Virus (HIV)-Infected Subjects
Official title: Safety and Immunogenicity of GlaxoSmithKline Biologicals' Herpes Zoster Vaccine 1437173A in Adult HIV-infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Herpes Zoster
Keywords: immunogenicity
vaccine
safety
HIV
Herpes Zoster
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-07-19
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Current use of HIV fusion inhibitors, chemokine (C-C motif) receptor (CCR5) inhibitors or Interleukin-2/ Interleukin-7/ Interferon;
* For subjects in the ART cohorts, any change in anti-retroviral drug regimen within 12 weeks prior to vaccination;
* Pregnant or lactating female;
* Female planning to become pregnant or planning to discontinue contraceptive precautions;
* Abnormal biochemical and hematological laboratory values obtained for blood samples collected at screening.

Primary outcomes:
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Month 0 to Month 18
measure: Number of Subjects With SAEs Related to Study Participation or to a Concurrent GSK Medication/Vaccine
timeFrame: From screening (up to 21 days prior to Month 0) until Month 18
measure: Number of Subjects With Any Fatal SAEs
timeFrame: From screening (up to 21 days prior to Month 0) until Month 18
measure: Number of Subjects With Any Adverse Events (AEs) of Specific Interest
timeFrame: From Month 0 until Month 18
measure: Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms
timeFrame: Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Unsolicited AEs
timeFrame: Within 30 days (Days 0-29) after each vaccination
measure: Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges
timeFrame: At Screening Visit (up to 21 days prior to Month 0)
measure: Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges
timeFrame: At Month 1
measure: Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges
timeFrame: At Month 2
measure: Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges
timeFrame: At Month 3
measure: Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges
timeFrame: At Month 6
measure: Number of Subjects With Any Hematological and Biochemical Parameters Below, Within or Above Normal Laboratory Ranges
timeFrame: At Month 7
measure: Number of Subjects With Any Significant Change in Antiretroviral Therapy (ART), Including Initiation of ART in ART-naïve Subjects
timeFrame: From Month 0 until Month 18
measure: Number of Subjects With Any AIDS-defining Condition
timeFrame: From Month 0 until Month 18
measure: Number of Subjects With Any Pre-defined Changes in HIV Viral Load (VL) and CD4 T-cell Count
timeFrame: From Month 1 to Month 7
measure: Number of Subjects With Any Significant Change in Antiretroviral Therapy (ART), Including Initiation of ART in ART-naïve Subjects, by HIV Status
timeFrame: From Month 0 to Month 18
measure: Number of Subjects With Any AIDS-defining Condition, by HIV Status
timeFrame: From Month 0 to Month 18
measure: Number of Subjects With Any Pre-defined Changes in HIV Viral Load (VL) and CD4 T-cell Count, by HIV Status
timeFrame: From Month 1 to Month 7
measure: Frequency of gE-specific CD4 T-cells
timeFrame: At Month 7
measure: -Anti-gE Antibody (Ab) Concentrations
timeFrame: At Month 7
Secondary outcomes:
measure: -Frequencies of Varicella-Zoster Virus (VZV)- and gE-specific CD4 T-cells
timeFrame: At Month 0, 1, 2, 3, 6, 7 and 18
measure: -Frequencies of Varicella-Zoster Virus (VZV)- and gE-specific CD4 T-cells, by HIV Status
timeFrame: At Months 0, 1, 2, 3, 6, 7 and 18
measure: -Anti-VZV and Anti-gE Antibody Concentrations
timeFrame: At Months 0, 1, 2, 3, 6, 7 and 18
measure: -Anti-VZV and Anti-gE Antibody Concentrations, by HIV Status
timeFrame: At Months 0, 1, 2, 3, 6, 7 and 18
measure: Number of Subjects With Any Herpes Zoster (HZ) Cases and Complications
timeFrame: From Month 0 until Month 18
measure: CD4 Count
timeFrame: At Screening Visit (up to 21 days prior to Month 0), Months 1, 2, 3, 6, 7 and 18
measure: HIV VL
timeFrame: At Screening Visit (up to 21 days prior to Month 0), Months 1, 2, 3, 6, 7 and 18
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Santa Fe
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Duesseldorf
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Woolwich, London
country: United Kingdom
facility: GSK Investigational Site
state: London
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.