Safety & Immunogenicity of GlaxoSmithKline Biologicals' Herpes Zoster Vaccine 1437173A

NCT00920218 | Completed Phase 2 Results

• 1 other identifier: 110258
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this observer-blind study is to evaluate the safety and immunogenicity of GlaxoSmithKline Biologicals' investigational Herpes Zoster vaccine GSK1437173A when administered as 2 doses or 3 doses to hematopoietic stem cell transplant (HCT) recipients.

Conditions

Herpes Zoster

Keywords

Vaccine; Safety; Herpes Zoster; Immunogenicity; Stem cell transplantation

Outcome Measures

Primary Outcomes (15)

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

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

  During the 7-days (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 \[including nausea, vomiting, diarrhoea and abdominal pain\], temperature \[defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], headache and myalgia. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature higher than (\>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

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

• Number of Subjects With Any and Grade 3 Unsolicited Adverse Events (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.

  During the 30-day (Days 0-29) post-vaccination period

• 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.

  Any time during the study up to Day 29 after the last vaccination

• 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.

  During the entire study period (from Day 0 up to Month 15)

• Number of Subjects With Any New Onset of Autoimmune Diseases (NOADs) and Other Immune Mediated Inflammatory Disorders

  Any new onset of autoimmune diseases and immune mediated inflammatory disorders were to be reported throughout the entire study period, whether or not they were considered to be possibly related to the treatment administration. These included neurological/demyelinating events, rheumatic and connective diseases, autoimmune endocrine diseases, inflammatory bowel diseases, autoimmune blood disorders, inflammatory skin disorders, other autoimmune/inflammatory events, autoimmune bullous skin diseases, vasculitis and liver autoimmune diseases.

  Within the 30-day (Days 0-29) post last vaccination period

• Number of Subjects With Any New Onset of Autoimmune Diseases (NOADs) and Other Immune Mediated Inflammatory Disorders

  Any new onset of autoimmune diseases and immune mediated inflammatory disorders were to be reported throughout the entire study period, whether or not they were considered to be possibly related to the treatment administration. These included neurological/demyelinating events, rheumatic and connective diseases, autoimmune endocrine diseases, inflammatory bowel diseases, autoimmune blood disorders, inflammatory skin disorders, other autoimmune/inflammatory events, autoimmune bullous skin diseases, vasculitis and liver autoimmune diseases.

  During the entire study period (from Day 0 to Month 15)

• Number of Subjects With Hematological and Biochemical Parameters With Respect to Normal Laboratory Ranges

  Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hemoglobin (HGB), Hematocrit (HCT), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLAT), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC).

  At Month 0

• Number of Subjects With Hematological and Biochemical Parameters With Respect to Normal Laboratory Ranges

  Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hemoglobin (HGB), Hematocrit (HCT), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLAT), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC).

  At Month 1

• Number of Subjects With Hematological and Biochemical Parameters With Respect to Normal Laboratory Ranges

  Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hemoglobin (HGB), Hematocrit (HCT), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLAT), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC).

  At Month 2

• Number of Subjects With Hematological and Biochemical Parameters With Respect to Normal Laboratory Ranges

  Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hemoglobin (HGB), Hematocrit (HCT), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLAT), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC).

  At Month 3

• Number of Subjects With Hematological and Biochemical Parameters With Respect to Normal Laboratory Ranges

  Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hemoglobin (HGB), Hematocrit (HCT), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLAT), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC).

  At Month 4

• Frequency of gE-specific Cluster of Differentiation 4 (CD4) T-cells Expressing at Least 2 Cytokines

  The analysis focused on CD4 T-cells expressing at least 2 cytokines among Interferon gamma \[IFN-γ\], Interleukin 2 \[IL-2\], Tumour Necrosis Factor alpha \[TNF-α\] and/or CD40 Ligand \[CD40L\] as determined by in vitro intracellular cytokine staining (ICS).

  At Month 4

• Anti-glycoprotein E (Anti-gE) Geometric Mean Antibody Concentrations

  Concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL).

  At Month 4

• Anti-gE Mean Antibody Concentrations

  Concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and are presented as mean concentrations, expressed in milli-international units per milliliter (mIU/mL).

  At Month 4

Secondary Outcomes (7)

• Frequency of CD4 T-cells Specific for Varicella Zoster Virus (VZV) Antigens

  At Months 0, 1, 2, 3, 4 and 15

• Frequency of gE-specific Cluster of Differentiation 4 (CD4) T-cells Expressing at Least 2 Cytokines

  At Months 0, 1, 2, 3 and 15

• Varicella Zoster Virus (VZV)-Specific Geometric Mean Antibody Concentrations

  At Months 0, 1, 2, 3, 4 and 15

• VZV-specific Mean Antibody Concentrations

  At Months 0, 1, 2, 3, 4 and 15

• Anti-gE Geometric Mean Antibody Concentrations

  At Months 0, 1, 2, 3 and 15

Study Arms (4)

GSK 1437173A F1 Group

EXPERIMENTAL

Male or female subjects, 18 years of age or older at the time of the first vaccination, received 3 doses of GSK 1437173A formulation 1 (F1) vaccine, administered intramuscularly in the upper deltoid region of non-dominant arm according to a 0,1,3-months schedule.

Biological: Herpes Zoster Vaccine 1437173A

GSK 1437173A F2 Group

EXPERIMENTAL

Male or female subjects, 18 years of age or older at the time of the first vaccination, received 3 doses of GSK 1437173A formulation 2 (F2) vaccine, administered intramuscularly in the upper deltoid region of non-dominant arm according to a 0,1,3-months schedule.

Biological: Herpes Zoster Vaccine 1437173A

Placebo-GSK 1437173A F1 Group

EXPERIMENTAL

Male or female subjects, 18 years of age or older at the time of the first vaccination, received 1 dose of the placebo followed by 2 doses of GSK 1437173A F1 vaccine. For some safety analyses, this Group was split into Placebo 1D Group (results following placebo administration) and GSK 1437173A 2D Group (results following HZV administration). All vaccines were administered intramuscularly in the upper deltoid region of non-dominant arm according to a 0,1,3-months schedule.

Biological: Herpes Zoster Vaccine 1437173A; Biological: Placebo vaccine (saline)

Placebo Group

PLACEBO COMPARATOR

Male or female subjects, 18 years of age or older at the time of the first vaccination, received 3 doses of placebo, administered intramuscularly in the upper deltoid region of non-dominant arm according to a 0,1,3-months schedule.

Biological: Placebo vaccine (saline)

Interventions

Herpes Zoster Vaccine 1437173A BIOLOGICAL

Different formulations of investigational vaccine (GSK 1437173A) administered in 2 or 3 doses intramuscularly.

GSK 1437173A F1 Group; GSK 1437173A F2 Group; Placebo-GSK 1437173A F1 Group

Placebo vaccine (saline) BIOLOGICAL

1 or 3 doses of Placebo (saline) injected intramuscularly.

Placebo Group; Placebo-GSK 1437173A F1 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;
• Serological evidence of prior VZV infection for all subjects born in 1980 or later and for subjects born outside the US before 1980 in a tropical or sub-tropical region. No testing for serological evidence of prior VZV infection is required for US subjects born before 1980;
• Has undergone autologous HCT within the past 50-70 days for treatment of Hodgkin lymphoma, non-Hodgkin lymphoma (T or B cell), myeloma or acute myeloid leukemia, and there are no plans for additional HCTs
• Written informed consent obtained from the subject;
• If the subject is female, she must be of non-childbearing potential or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.

You may not qualify if:

• Use of any investigational 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;
• Administration or planned administration of a vaccine that is not part of the study protocol since transplantation. However licensed non-replicating vaccines (i.e. inactivated and subunit vaccines, including inactivated and subunit influenza vaccines, with or without adjuvant) may be administered up to 8 days prior to dose 1;
• Administration of immunoglobulins since transplantation;
• Previous vaccination against varicella or HZ;
• History of HZ within the previous 12 months;
• Known exposure to VZV since transplantation;
• Evidence of active infection at the time of enrollment including a temperature of ≥ 37.5° C or any serious HCT-related complication;
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine;
• Hypersensitivity or intolerance to acyclovir or valacyclovir;
• Pregnant or lactating female.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (11)

GSK Investigational Site

Little Rock, Arkansas, 72205, United States

Location

GSK Investigational Site

Duarte, California, 91010, United States

Location

GSK Investigational Site

San Francisco, California, 94143, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02115, United States

Location

GSK Investigational Site

Minneota, Minnesota, 55455, United States

Location

GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27599, United States

Location

GSK Investigational Site

Durham, North Carolina, 27705, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44195, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Stadtmauer EA, Sullivan KM, Marty FM, Dadwal SS, Papanicolaou GA, Shea TC, Mossad SB, Andreadis C, Young JA, Buadi FK, El Idrissi M, Heineman TC, Berkowitz EM. A phase 1/2 study of an adjuvanted varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients. Blood. 2014 Nov 6;124(19):2921-9. doi: 10.1182/blood-2014-04-573048. Epub 2014 Sep 18.

  PMID: 25237196 DERIVED

MeSH Terms

Conditions

Herpes Zoster

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

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: June 12, 2009
• First Posted: June 15, 2009
• Study Start: July 14, 2009
• Primary Completion: April 26, 2011
• Study Completion: March 21, 2012
• Last Updated: December 12, 2017
• Results First Posted: December 12, 2017

Record last verified: 2017-08

Locations

US (11)