A Study to Evaluate the Efficacy, Safety and Immunogenicity of a Vaccine Designed to Protect Against Infection With Shigella Sonnei in Healthy Adults

NCT03527173 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 205626H03_03TP
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy, safety and immunogenicity of the GSK3536852A vaccine, which was designed to protect against shigellosis caused by Shigella sonnei (S. sonnei) and is using the new Generalized Modules for Membrane Antigens (GMMA) platform technology developed by GlaxoSmithKline (GSK) Vaccines Institute for Global Health (GVGH). The study vaccine could be the stepping stone for the development of a multivalent broadly protective Shigella vaccine for vaccination of impoverished communities where shigellosis is endemic. However, a standalone monovalent vaccine against S. sonnei could be used to protect travelers against diarrheal shigellosis, as the vast majority of travelers' shigellosis is caused by S. sonnei, and even to protect infants in endemic regions where shigellosis is primarily caused by S. sonnei. The GSK3536852A vaccine has been tested in two Phase I dose escalation studies in Europe to assess its safety and immunogenicity via three routes of administration: intramuscular (IM), intranasal (IN) and intradermal (ID). The results from the first study (dose escalation with IM vaccination) have shown that the vaccine has an acceptable safety profile and is well-tolerated up to a dose of 100 micrograms (µg). The results from the second study (dose escalation with ID, IN and IM vaccination) showed that GSK3536852A vaccine is well-tolerated also when administered by the ID and IN routes of vaccination. However, immunogenicity data have shown that GSK3536852A vaccine administered by the ID and IN routes is not as immunogenic as GSK3536852A vaccine administered by the IM route. Therefore, it has been decided to proceed with the clinical development program of this vaccine only using the IM vaccination route. In terms of dosage, the regimen tested in Phase I studies (three doses given one month apart) did not show any significant benefit from the third dose in terms of immunogenicity, therefore a two dose schedule was selected for next studies. A Phase IIa study, conducted in endemic regions of Africa (i.e., Kenya), has been completed and confirmed the acceptable safety profile and immunogenicity of GSK3536852A vaccine. Performing this vaccine-human challenge study may give the opportunity to establish evidence of clinical protection induced by the candidate S. sonnei vaccine (GSK3536852A vaccine) at an early development stage.

Conditions

Dysentery, Bacillary

Keywords

Challenge; Efficacy; Shigellosis; Vaccination

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects With at Least One Episode of Shigellosis According to the Protocol Primary Case Definition

  Attack rate of shigellosis expressed as percentage of subjects with at least one episode of shigellosis after challenge, and 90% confidence interval (CI) (Clopper-Pearson method). Episodes of shigellosis fulfilling primary case definition: Shedding of S. sonnei 53G accompanied by moderate or severe diarrhea OR shedding with oral temperature greater than or equal to (≥) 38.5°C. Moderate diarrhea consists of 4 to 5 loose or watery (Grade \[G\]3 to 5) stools or 400 to 800 grams of G3 to 5 stools within 24 hours. Severe diarrhea consists of 6 or more loose or watery (G3 to 5) stools or \> 800 grams of G3 to 5 stools within 24 hours or required medical intervention. In case of severe diarrhea, medical intervention is defined as intravenous fluids administration or anticipation of antibiotic treatment before the 5th day after challenge. G3 = viscous opaque liquid or semi-liquid which assumes the shape of the bowl; G4 = watery opaque liquid; G5 = clear watery or mucoid liquid.

  Starting with the challenge visit (Day 57) and lasting up to the end of the inpatient stay (Day 64)

Secondary Outcomes (18)

• Percentage of Subjects With at Least One Episode of Shigellosis According to Controlled Human Infection Model (CHIM) Working Group Case Definition for Shigellosis

  Starting with the challenge visit (Day 57) and lasting up to the end of the inpatient stay (Day 64)

• Percentage of Subjects With at Least One Episode of Shigellosis

  Starting with the challenge visit (Day 57) and lasting up to the end of the inpatient stay (Day 64)

• Percentage of Subjects With at Least One Episode of More Severe Shigellosis

  Starting with the challenge visit (Day 57) and lasting up to the end of the inpatient stay (Day 64)

• Percentage of Subjects With Specific Disease Symptoms

  Starting with the challenge visit (Day 57) and lasting up to the end of the inpatient stay (Day 64)

• Mean Number of Grade 3-5 Stools Per Subject

  Starting with the challenge visit (Day 57) and lasting up to the end of the inpatient stay (Day 64)

Study Arms (2)

S. sonnei Group

EXPERIMENTAL

Male or female subjects between, and including, 18 and 50 years of age at the time of the first vaccination, received 2 doses of the S. sonnei study vaccine at Day 1 and Day 29 respectively, by intramuscular injection into the upper deltoid region of the non-dominant arm. At 28 days after the second dose (Day 57), subjects received the challenge dose of S. sonnei 53G strain, orally.

Biological: S.sonnei vaccine; Biological: S. sonnei 53G challenge strain

Placebo Group

PLACEBO COMPARATOR

Male or female subjects between, and including, 18 and 50 years of age at the time of the first vaccination, received 2 doses of the placebo at Day 1 and Day 29 respectively, by intramuscular injection into the upper deltoid region of the non-dominant arm. At 28 days after the second dose (Day 57), subjects received the challenge dose of S. sonnei 53G strain, orally.

Drug: Placebo; Biological: S. sonnei 53G challenge strain

Interventions

S.sonnei vaccine BIOLOGICAL

Subjects receiving 2 doses of the study vaccine by intramuscular route, 28 days apart (at Day 1 and Day 29).

Also known as: GSK3536852A vaccine

S. sonnei Group

Placebo DRUG

Subjects receiving 2 doses of placebo by intramuscular route, 28 days apart (at Day 1 and Day 29).

Also known as: GAHB-Placebo

Placebo Group

S. sonnei 53G challenge strain BIOLOGICAL

Subjects receiving the challenge dose of S. sonnei 53G strain, orally, at Day 57.

Placebo Group; S. sonnei Group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject prior to performing any study specific procedure.
• Individuals who, after the nature of the study has been explained to them, have shown adequate comprehension of the study procedures and knowledge of study.
• A male or female between, and including, 18 and 50 years of age at the time of the first vaccination.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Seronegative for human immunodeficiency virus (HIV), hepatitis B and C.
• Female subjects of non-childbearing potential may be enrolled in the study.
• 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 study period.

You may not qualify if:

• Received an investigational or non-registered medicinal product within 30 days prior to informed consent, or planned use during the study period.
• Any 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.
• History of any neurological disorders or seizures.
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study.
• Human Leukocyte Antigen (HLA)-B27 positive test at screening and/or with history of reactive arthritis.
• Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine/placebo dose. For corticosteroids, this will mean prednisone ≥ 20 milligrams (mg)/day, or equivalent. Inhaled except for doses \> 800 µg/day and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs at any time during the study period. Subjects may be on chronic or as needed medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition.
• Known bleeding diathesis or any condition that may be associated with a prolonged bleeding time.
• 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 vaccine/product.
• History of having participated in a previous Shigella challenge study.
• Individuals who have a previously laboratory confirmed case of disease caused by S. sonnei or serology positive for local anti S. sonnei LPS IgG Screening-ELISA at screening.
• History of any serious chronic or progressive disease according to judgment of the investigator.
• History of any malignancy or lymphoproliferative disorder.
• Known to be part of study personnel or being a close family member to the personnel conducting this study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Dysentery, Bacillary

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@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
• Masking Details: Observer-blind The subject, the site and sponsor personnel involved in the clinical evaluation of the subjects are blinded while other study personnel may be aware of the treatment assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2018
• First Posted: May 17, 2018
• Study Start: August 29, 2018
• Primary Completion: May 8, 2019
• Study Completion: November 11, 2019
• Last Updated: July 28, 2020
• Results First Posted: May 15, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• 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

US (1)