A Phase 1 interventional study of ShigETEC live, attenuated, oral vaccine and Placebo in Diarrheal Disease, Infectious, Gastrointestinal Disease and Reactive Arthritis, sponsored by Eveliqure Biotechnologies GmbH. Completed at 1 site in Hungary. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-06-08.
Sponsored by Eveliqure Biotechnologies GmbH · Phase 1, Interventional, and Prevention
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.
ShigETEC vaccine is intended to stimulate an immune response in which protective antibodies are generated that prevent infection if a vaccinee is subsequently exposed to Shigella and ETEC.
Main objective of the study:
In Stage 1 is to determine Maximum Tolerated Single Dose of ShigETEC vaccine. Determine optimal immunogenicity of single dose in dose escalation.
In Stage 2 is to determine safety of multiple dose regimens of ShigETEC Determine number of doses for maximum immune response to Shigella and ETEC.
In both stages to determine the duration of shedding.
Stage 1 is conducted in an inpatient hospital setting at a single site through Day 6. A total of 48 subjects (2 vaccine recipients to each placebo recipient) are to be enrolled sequentially in 4 different ascending dose groups (12 subjects per group) to receive a single oral dose of the ShigETEC vaccine starting at a dose in the first group of 1 x 10\^9 Colony Forming Units (CFU) of vaccine or a placebo. Each group will have baseline serum and stool samples collected at the time of admission, but in any case, before vaccination. Following 12-16 hours, they would receive oral immunization followed by evaluation of acute safety and tolerability for 6 days. Provided that no stopping rules are met through 6 days of follow-up for the entire group then the next group would be enrolled until all 4 groups were enrolled and evaluated through 6 days of assessment. Subjects in each group would be discharged to outpatient follow-up 6 days after dosing (7 days in hospital) if they were asymptomatic for shigellosis-like illness. Any subject with symptomatic illness would be treated with an appropriate course of antibiotic at the time of discharge. Daily stools will be tested for the presence of the ShigETEC vaccine until at least 2 sequential specimens are negative. If shedding persists through 14 days then the participant would be treated with antibiotics regardless of any symptomatology. All subjects would then be followed through 60 days following immunization to collect adverse events and blood samples.
Stage 2 of the study is an outpatient double-blind, placebo-controlled study. In this stage, a total of 36 subjects (2 vaccine recipients to each placebo recipient) will be enrolled in 3 different groups (12 subjects per group). The optimal dose and schedule of ShigETEC will be determined by analysis of the safety, shedding, and immunogenicity of each of the immunization schedules and interval of 3 days between doses (e.g dosing on days 1, 4, 7 and 10 for four doses.) Each group will be enrolled and followed for acute safety and tolerability from the first dose of vaccine through 6 days following the last dose of vaccine administered in their schedule and then for 60 days following the last dose of vaccine for other adverse events. Blood for serum immunogenicity studies will be obtained pre-immunization and at 6, 10, 28, and 60 days following the last immunization. Stool samples for evaluation of vaccine shedding will be collected as available (with a target of daily) through up to 14 days following the last dose of vaccine/placebo. Stool samples pre immunization and at or nearest to days 10 and 28 after the last vaccine dose for each group were evaluated for IgA titers to vaccine components. Collection of stool samples for determining vaccine shedding were terminated after two sequential negative samples after day 6 following the last dose.
44 studies on the registry are indexed under Dysentery; 6 are open to participants now.
This study's enrollment of 84 is below the median of 163 across 38 interventional studies indexed under Dysentery.
Browse Dysentery studies →Eveliqure Biotechnologies GmbH is the lead sponsor of 3 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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.
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.
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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: Days 0 to 6
Immunogenicity assessment - serum
Serum IgA and IgG response to ShigETEC lysate, LTB and ST by ELISA
Time frame: Day 0 and days 6, 10, 28, 60 after the last vaccination
Immunogenicity assessment - ALS
ALS IgA response to ShigETEC lysate, LTB and ST by ELISA
Time frame: Day 0 and days 6, 10 after the last vaccination
Immunogenicity assessment - stool extract
Fecal IgA response to ShigETEC lysate, LTB and ST by ELISA; Fecal total IgA content by ELISA
Time frame: Day 0 and days 10, 28 after the last vaccination
Plan to share: Undecided
Ran from Sep 2020 to primary completion in Jun 2021, 9 months.
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Eveliqure Biotechnologies GmbH