Phase 1 Trial for Safety, Tolerability, and Immunogenicity of a Live, Attenuated, Oral Shigella/ETEC Combination Vaccine to Healthy Adults

NCT05409196 | Completed Phase 1

• 1 other identifier: EVQ 101
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 dose escalating study to assess the safety, tolerability, and immunogenicity of ShigETEC, a live, attenuated Shigella/ETEC combination vaccine given orally to healthy European adults 18 to 45 years of age. The major aim is the development of an efficacious and safe vaccine that prevents diarrhea caused by Shigella and ETEC in travelers, military personal visiting endemic countries and children of the developing world. This Phase 1 safety and immunogenicity study used a double-blind, placebo-control design and was conducted in two stages, a single ascending and a multiple ascending stage.

Conditions

Diarrheal Disease, Infectious; Gastrointestinal Disease; Reactive Arthritis

Keywords

Shigellosis

Outcome Measures

Primary Outcomes (7)

• Number and percentage of participants with treatment related acute adverse events post vaccination

  Acute gastrointestinal and systemic illness symptoms following immunization(s)- treatment related Adverse events according to CTCAE v4.0 including nausea, vomiting, diarrhoea, abdominal pain, fever, joint ache, muscle/joint aches, fatigue/malaise, headache, loss of appetite.

  Day 1-6 following each vaccination

• Number and percentage of participants with any adverse event.

  Number and percentage of participants with adverse event according to CTCAE v4.0 occuring during the entire study period

  until 60 days after the last vaccination (max 60 days in stage 1)

• Number and percentage of participants with any adverse event.

  Number and percentage of participants with adverse event according to CTCAE v4.0 occuring during the entire study period

  until 60 days after the last vaccination (max 110 days in stage 2)

• Number and percentage of participants with serious adverse event.

  Number and percentage of participants with serious adverse event occurring during the entire study period in stage 1

  until 60 days after the last vaccination (max 60 days in stage 1)

• Number and percentage of participants with serious adverse event.

  Number and percentage of participants with serious adverse event occurring during the entire study period in stage 2

  until 60 days after the last vaccination (max 110 days in stage 2)

• Number and percentage of participants with Vaccine Shedding

  Fecal shedding of vaccine - duration of detectable presence of ShigETEC in stool by polymerase chain reaction (PCR) and/or culture.

  14 days after last immunization

• Reactogenicity

  Reactogenicity events accumulated through day 6 for acute safety and tolerability in acute changes in reactogenicity events at a scale (none or mild or moderate or severe) or an absolute value: * Temperature: degrees Celsius (°C) * Nausea: none/mild/moderate/severe * Vomiting: none/mild/moderate/severe * Diarrhea: none/mild/moderate/severe * Number of stools: discrete value * Abdominal pain: none/mild/moderate/severe * Muscle/joint aches: none/mild/moderate/severe * Tiredness/fatigue/malaise: none/mild/moderate/severe * Headache: none/mild/moderate/severe * Loss of appetite: none/mild/moderate/severe * Chills: none/mild/moderate/severe * Difficulty sleeping: none/mild/moderate/severe * Dizziness: none/mild/moderate/severe * Difficulty swallowing: none/mild/moderate/severe

  Days 0 to 6

Secondary Outcomes (3)

• Immunogenicity assessment - serum

  Day 0 and days 6, 10, 28, 60 after the last vaccination

• Immunogenicity assessment - ALS

  Day 0 and days 6, 10 after the last vaccination

• Immunogenicity assessment - stool extract

  Day 0 and days 10, 28 after the last vaccination

Study Arms (2)

ShigETEC vaccine

EXPERIMENTAL

In Stage 1 subjects will be allocated randomly to one of four study cohorts to receive a single oral dose of one of four escalating dose levels of ShigETEC vaccine (ShigETEC 1x10\^9 CFU, ShigETEC 1x10\^10 CFU, ShigETEC 5x10\^10 CFU, ShigETEC 2x10\^11 CFU). 8 subjects per dose group will be administered. Subjects in Stage 2 will be enrolled sequentially by group and allocated randomly to one of three study cohorts determined from Stage 1 to receive either two, three or four doses of the 5x10\^10 ShigETEC vaccine at 3-day interval. 8 subjects per dose group will be administered.

Biological: ShigETEC live, attenuated, oral vaccine

Placebo

PLACEBO COMPARATOR

In Stage 1: 4 subjects in each dose group will receive a single oral dose of placebo In Stage 2: 4 subjects in each cohort will either receive 2, 3 or 4 doses of placebo at 3-day intervals.

Drug: Placebo

Interventions

ShigETEC live, attenuated, oral vaccine BIOLOGICAL

Vaccine or placebo will be delivered orally as a single dose in Stage 1 and between 2 and 4 doses at 3-day intervals in Stage 2 of the Study.

ShigETEC vaccine

Placebo DRUG

Vaccine or placebo will be delivered orally as a single dose in Stage 1 and between 2 and 4 doses at 3-day intervals in Stage 2 of the Study.

Placebo

Eligibility Criteria

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

You may qualify if:

• Generally healthy male and non-pregnant, non-nursing female adults aged 18 to 45 years
• Who are determined by medical history, physical examination and clinical judgment to be eligible for this study;
• Who provide written informed consent after the nature of the study had been explained;
• Who are available for the two to three months duration of follow-up (from enrolment to study completion);
• Who are available to be interviewed by study staff for the 2-month post-immunization follow-up;

You may not qualify if:

• Subjects who are perceived to be unavailable or difficult to contact for evaluation or study visits during the study period;
• Who have a known or suspected disease of cancer (excluding healed skin lesions), the immune system, or those who are receiving immunosuppressive therapy, including systemic corticosteroids or cytotoxic agents;
• Who have received any blood products, including immunoglobulin, in the period from six months prior to vaccination or are anticipated to receive such products through to the conclusion of the study;
• Who have ever received a cholera vaccine;
• Who are receiving antibiotics or completed antibiotic therapy in previous 7 days;
• Who have or are participating in or have concluded participation in a clinical research study in the last 30 days or have not cleared the experimental product or the biological effects of such experimental products prior to vaccination or received a licensed vaccine in the 30 days prior to vaccination;
• Who have a chronic non-gastrointestinal medical condition (e.g. hypertension, hyperlipidemia) that is not well controlled with medication;
• Who have significant abnormality of blood chemistry, hematology, or screening tests (including tests for hepatitis B, HIV, HCV);
• Who have a history of reactive arthritis following GI infection;
• Who expect to work in the subsequent 2 weeks as a food handler or in direct patient, child day care, or elder care;
• Who have immunocompromised household member;
• Who have ever had a diagnosed Shigella or ETEC infection;
• Who have developed symptoms of Shigella or ETEC infections after having travelled to Shigella or ETEC endemic areas in the past 12 months;
• Who have any condition which in the opinion of the investigator puts the subject at risk of non-compliance with the protocol;
• Who have known allergy to quinolone or azithromycin that will be used in the study;

Sponsors & Collaborators

• Eveliqure Biotechnologies GmbH: lead

Study Sites (1)

Debreceni Egyetem, Klinikai Központ, Belgyógyászati Klinika, Klinikai Farmakológiai Részleg

Debrecen, Hungary

Location

Related Publications (1)

• Harutyunyan S, Neuhauser I, Mayer A, Aichinger M, Szijarto V, Nagy G, Nagy E, Girardi P, Malinoski FJ, Henics T. Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC. Vaccines (Basel). 2020 Nov 16;8(4):689. doi: 10.3390/vaccines8040689.

  PMID: 33207794 RESULT

MeSH Terms

Conditions

Dysentery; Gastrointestinal Diseases; Arthritis, Reactive; Dysentery, Bacillary

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Gastroenteritis; Digestive System Diseases; Intestinal Diseases; Arthritis, Infectious; Infections; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Dénes Páll, MD, PhD

  University of Debrecen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: June 8, 2022
• Study Start: September 16, 2020
• Primary Completion: June 21, 2021
• Study Completion: June 21, 2021
• Last Updated: June 8, 2022

Record last verified: 2022-06

Locations

HU (1)