A Study of the Safety and Immune Response of 2 Doses of a New Shigella Vaccine in Kenyan Adults

NCT02676895 | Completed Phase 2 Results DMC

• 2 other identifiers: 205494H03_04TP
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and the immunogenicity of two different doses of the GVGH S. sonnei vaccine in healthy adults and represents the first step towards testing of the GMMA vaccine in the vaccine target population of children from developing countries where shigellosis is endemic.

Conditions

Shigella Sonnei Infection

Outcome Measures

Primary Outcomes (8)

• Number of Subjects With Solicited Local and Systemic Adverse Reactions After Each Vaccination

  Assessed solicited local adverse reactions were injection site erythema, induration, pain. Assessed systemic adverse reactions were headache, arthralgia, chills, fatigue, malaise, myalgia and temperature (body temperature measured axillary). Any = occurrence of the symptom regardless of intensity grade. Any temperature = body temperature ≥ 38.0°C. Severe symptom = pain, headache, arthralgia, chills, fatigue, malaise and myalgia that prevented normal activity. Severe redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. Severe temperature = body temperature \> 40.0 °C.

  From 30 minutes up to 7 days following each vaccination

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

  An unsolicited AE is an AE that was not solicited using the Diary Card and that was spontaneously communicated by a subject who has signed the informed consent. Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider), or were of concern to the subject. Note: \*disruptions= dose reduction, interruption or delay in study vaccination.

  During 28 days following each vaccination

• Number of Subjects With Serious Adverse Events (SAEs)

  An SAE is defined as any untoward medical occurrence that at any dose results in one or more of the following: death; is life-threatening (i.e., the subject was, in the opinion of the investigator, at immediate risk of death from the event as it occurred); it does not refer to an event which hypothetically might have caused death if it were more severe; required or prolonged hospitalization; persistent or significant disability/incapacity (i.e., the event causes a substantial disruption of a person's ability to conduct normal life functions); congenital anomaly/or birth defect; an important and significant medical event that may not be immediately life-threatening or resulting in death or hospitalization but, based upon appropriate medical judgment, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above.

  Throughout the whole study period (from Day 1 up to Day 57)

• Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 8 by Baseline Ranges

  The safety laboratory data included haematological parameters (basophils, eosinophils, erytrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, platelets and neutrophils), and chemical parameters (Alkaline Phosphatase \[ALP\], Alanine Aminotransferase \[ALA\], Aspartate Aminotransferase \[AST\], Bilirubin \[BILI\], Blood Urea Nitrogen \[BUN\], Creatinine \[CREAT\], Gamma Glutamyl Transferase \[GGT\], Glucose \[GLUC\], Potassium \[K\], Lactate Dehydrogenase \[LDH\] and Sodium \[Na\]). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 8 (7 days after first vaccination)

• Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 29 by Baseline Ranges

  The safety laboratory data included haematological parameters (basophils, eosinophils, erytrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, platelets and neutrophils), and chemical parameters (Alkaline Phosphatase \[ALP\], Alanine Aminotransferase \[ALA\], Aspartate Aminotransferase \[AST\], Bilirubin \[BILI\], Blood Urea Nitrogen \[BUN\], Creatinine \[CREAT\], Gamma Glutamyl Transferase \[GGT\], Glucose \[GLUC\], Potassium \[K\], Lactate Dehydrogenase \[LDH\] and Sodium \[Na\]). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 29 (28 days after the first vaccination)

• Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 36 by Baseline Ranges

  The safety laboratory data included haematological parameters (basophils, eosinophils, erytrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, platelets and neutrophils), and chemical parameters (Alkaline Phosphatase \[ALP\], Alanine Aminotransferase \[ALA\], Aspartate Aminotransferase \[AST\], Bilirubin \[BILI\], Blood Urea Nitrogen \[BUN\], Creatinine \[CREAT\], Gamma Glutamyl Transferase \[GGT\], Glucose \[GLUC\], Potassium \[K\], Lactate Dehydrogenase \[LDH\] and Sodium \[Na\]). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 36 (7 days after the second vaccination)

• Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 57 by Baseline Ranges

  The safety laboratory data included haematological parameters (basophils, eosinophils, erytrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, platelets and neutrophils), and chemical parameters (Alkaline Phosphatase \[ALP\], Alanine Aminotransferase \[ALA\], Aspartate Aminotransferase \[AST\], Bilirubin \[BILI\], Blood Urea Nitrogen \[BUN\], Creatinine \[CREAT\], Gamma Glutamyl Transferase \[GGT\], Glucose \[GLUC\], Potassium \[K\], Lactate Dehydrogenase \[LDH\] and Sodium \[Na\]). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 57 (28 days after the second vaccination)

• Number of Subjects With Reported Reactive Arthritis or Neutropenia (AESIs)

  Reactive arthritis is defined as non-purulent joint inflammation that develops in response to an infection in another part of the body. Since the inflammation is triggered by a previous condition, it is termed "reactive". Intestinal pathogens that have been associated with reactive arthritis include Campylobacter, Salmonella, Yersinia, Clostridium difficile, and Shigella. If reactive arthritis is caused by an auto immune response, there is at least a possibility that it could be initiated by vaccination of susceptible people with the 1790GAHB vaccine.

  Throughout the whole study period (from Day 1 up to Day 57)

Secondary Outcomes (4)

• Anti-LPS S.Sonnei IgG ELISA Geometric Mean Concentrations (GMCs), by Baseline Titer

  At Day 1, Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination)

• Anti-LPS S. Sonnei Geometric Mean Ratios (GMRs) Between Post- and Pre-vaccination Samples

  At Day 1, Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination)

• Number of Subjects With Seroresponse to Anti-LPS S. Sonnei IgG ELISA, by Baseline Titer

  At Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination)

• Number of Subjects With Titers Post Vaccination Concentration for Anti-LPS S. Sonnei ≥ 121 U/mL

  At Day 1, Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination)

Study Arms (3)

1790GAHB 25 μg Group

EXPERIMENTAL

Subjects who received 2 injections of 1790GAHB vaccine containing 25 μg of S. sonnei.

Biological: GVGH S. sonnei (1790GAHB) vaccine 25 μg

1790GAHB 100 μg Group

EXPERIMENTAL

Subjects who received 2 injections of 1790GAHB vaccine containing 100 μg of S. sonnei.

Biological: GVGH S. sonnei (1790GAHB) vaccine 100 μg

Control Group

ACTIVE COMPARATOR

Subjects who received one dose of Menveo vaccine and a second dose of Boostrix vaccine.

Biological: Menveo; Biological: Boostrix

Interventions

GVGH S. sonnei (1790GAHB) vaccine 25 μg BIOLOGICAL

Two injections of the study vaccine were administered 28 days apart.

1790GAHB 25 μg Group

GVGH S. sonnei (1790GAHB) vaccine 100 μg BIOLOGICAL

Two injections of the study vaccine were administered 28 days apart.

1790GAHB 100 μg Group

Menveo BIOLOGICAL

One injection of Menveo was administered in subjects in the Control Group.

Control Group

Boostrix BIOLOGICAL

One injection of Boostrix was administered in subjects in the Control Group.

Control Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Individuals ≥18 years to ≤45 years of age on the day of informed consent who are resident in the study area and are not planning to leave during the study period.
• Individuals who, after the nature of the study has been explained, have voluntarily given written consent according to local regulatory requirements, prior to study entry.
• Individuals who can comply with study procedures including follow-up.
• Individuals in good health as determined by the outcome of medical history, physical examination, hematology, renal function, and liver function tests, urine dipstick/urinalysis and the clinical judgment of the investigator.

You may not qualify if:

• Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
• Individuals with any progressive or severe neurological disorder, seizure disorder or previous Guillain-Barré syndrome.
• Individuals who, in the judgment of the investigator, may not be able to comply with all the required study procedures.
• Individuals with history of any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.
• Individuals with history of reactive arthritis.
• Individuals with known HIV or hepatitis B virus infection or HIV related disease, history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system. Individuals under systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to screening.
• Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
• Individuals with a neutrophil count lower than 1.8 x 10\^9/L (applicable to the initial 18 subjects) or lower than 1.0 x 10\^9/L (applicable to the additional subjects if approved by DSMB) at screening
• Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, Type 2 diabetes mellitus, hypertension, cardiac, renal or hepatic disease and tuberculosis).
• Individuals who have any malignancy or lymphoproliferative disorder.
• Individuals with history of allergy to vaccines components or any other allergies deemed by the investigator to increase the risk of an adverse event if they were to participate in the trial.
• Individuals participating in any clinical trial with another investigational product within 28 days prior to the screening study visit or intent to participate in another clinical study at any time during the conduct of this study.
• Individuals who received vaccines containing meningococcal A, C, W, Y or tetanus, diphtheria or pertussis antigens within 12 months before screening, or any other vaccines within 4 weeks prior to screening in this study or who are planning to receive any vaccine within the entire study duration.
• Individuals who have received blood, blood products, and/or plasma derivatives including parenteral immunoglobulin preparations in the 12 weeks prior to the first dose of the study vaccine.
• Individuals who are study personnel or immediate family members (parents, children, spouse and brothers/sisters) to the personnel conducting this study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Kilifi, 80108, Kenya

Location

Related Links

• IPD for this study will be made available via the Clinical Study Data Request site.

MeSH Terms

Interventions

Vaccines; Meningococcal Vaccines; Boostrix

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures; Bacterial Vaccines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

antonella.s.scire@gsk.com

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2016
• First Posted: February 8, 2016
• Study Start: August 8, 2016
• Primary Completion: March 10, 2017
• Study Completion: March 10, 2017
• Last Updated: February 18, 2019
• Results First Posted: February 18, 2019

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

KE (1)