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Shigella CVD 31000: Study of Responses With Shigella-ETEC Vaccine Strain CVD 1208S-122

Primary Purpose

Shigella Infection, Enterotoxigenic Escherichia Coli Infection

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
strain CVD 1208S-122
Placebo
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Shigella Infection focused on measuring vaccine, strain CVD 1208S-122

Eligibility Criteria

18 Years - 49 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Male or female, 18 - 49 years of age
  • Written informed consent provided
  • Determined to be in good health* based on medical history and review of concomitant medications

    *Good health as defined by an absence of an active chronic medical condition which requires daily prescription medication(s). Participants may be eligible if the medical condition only requires infrequent as needed (PRN) medication and if the investigator determines that the condition does not pose a risk to participant safety or the assessment of reactogenicity and immunogenicity. Any chronic medical condition which does not require a daily prescription medication but might pose a risk to a participant with rapid dehydration (i.e., rapid intravascular volume changes) would be ineligible to participate.

  • Documented acceptable results from screening laboratory work (defined in Appendix B), including:

    • Complete blood count (CBC) with differential for total white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (Hg), platelet count
    • Creatinine, alanine aminotransferase (ALT), total bilirubin
    • Serum Immunoglobulin A (IgA) level
    • Human immunodeficiency virus (HIV) antibody, Hepatitis B surface antigen (HBsAg), Hepatitis C virus antibody (HCV)
    • HLA-B27 histocompatibility testing
    • Serum Beta human chorionic gonadotropin (β-HCG) test, if the participant is a woman of child-bearing potential
  • A passing score (≥70%) on a Comprehension Assessment Tool
  • Agrees not to participate in another clinical trial during the study period
  • Females of child-bearing potential† agree to use an acceptable form of birth control‡ from enrollment and through at least 4 weeks after vaccination

    †Females of child-bearing potential, defined as having not been sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure® placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or <1 year has passed since the last menses, if menopausal.

    ‡Acceptable birth control includes barrier methods such as condoms or diaphragms/cervical cap with spermicide; effective intrauterine devices; NuvaRing®; and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill") or alternatively, monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the study vaccination, abstinence from sexual intercourse with a male partner, or sexual relationships with non-male partners.

  • Available for up to a 6-day inpatient stay
  • For Participants of Cohorts 1-3 during the time when a U.S. Public Health Emergency for COVID-19 exists, SARS-CoV-2 testing must be performed upon admission to the inpatient ward and must document a negative test result prior to vaccination.

Exclusion Criteria:

  • A positive pregnancy test at screening or within 24 h prior to study product dosing
  • A female who is breastfeeding
  • Poor venous access, as defined by inability to obtain venous blood, for screening labs, after 3 venipuncture attempts
  • Abnormal vital signs, defined as:

    • Systolic BP >150 mmHg or Diastolic BP >90 mmHg
    • Resting heart rate >100 bpm
    • Oral temperature ≥38.0°C
  • Having received prior vaccines for or have had prior infection with ETEC, LT, cholera, or Shigella, within the past 3 years
  • History of diarrhea during travel to a developing country within the past 3 years
  • History of chronic gastrointestinal illness, including severe dyspepsia, lactose intolerance, or another significant gastrointestinal tract disease (e.g., irritable bowel syndrome, inflammatory bowel syndrome, gastric ulcer disease)
  • Regular use (≥once weekly) of laxatives, anti-diarrheal agents, anti-constipation agents, or antacid therapies
  • History of major gastrointestinal surgery (uncomplicated laparoscopic appendectomy or cholecystectomy >1-year prior is permitted)
  • Abnormal bowel habits, as defined by <3 stools per week or >2 stools per day in the past 6 months
  • Use of systemic antimicrobials§ within the past 2 weeks

    • use of topical (skin), otic, or ophthalmic antibiotics is acceptable, if those doses are not expected to result in significant systemic absorption levels
  • Use of oral, parenteral or high-dose inhaled steroids within 30 days
  • Use of any medication which might affect immune function# within 30 days

    #examples include anti-cancer drugs, immunomodulating monoclonal antibody therapeutics, and rheumatologic therapies

  • Diagnosis of schizophrenia or other major psychiatric disease
  • Alcohol or drug abuse within last 5 years
  • Presence of immunosuppression, which could be due to active neoplastic disease or a history of any hematologic malignancy (excluding resolved non-melanoma skin cancers), radiation therapy, or primary or secondary immunodeficiencies
  • History of allergy to quinolone (e.g., ciprofloxacin) or sulpha drugs (e.g., trimethoprim-sulfamethoxazole)
  • Known history of seizure disorder (remote history of a childhood seizure disorder which has completely resolved is acceptable)
  • Occupation involving the handling of ETEC, cholera, or Shigella bacteria
  • Occupation in food handling industry or care of very young children (<2 years old), elderly (≥70 years), or immunocompromised
  • During the time when a U.S. Public Health Emergency for COVID-19 exists, within 14 days prior to the time of vaccination, the presence of 2 or more of any of the following symptoms: fever (≥38°C, chills, myalgia, headache, sore throat, or new olfactory and taste disorder
  • During the time when a U.S. Public Health Emergency for COVID-19 exists, within 14 days prior to the time of vaccination, the presence of 1 or more of any of the following respiratory symptoms: cough which cannot otherwise be explained, shortness of breath, or difficulty breathing
  • Any other criteria which, in the investigator's opinion, would compromise the safety of the study, the ability of a subject to participate, or the results of the study

Sites / Locations

  • University of Maryland, Baltimore, University of Maryland School of Medicine, Center for Vaccine Development and Global HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1: Shigella Vaccine at 10^8 cfu or Placebo

Cohort 2: Shigella Vaccine at 10^9 cfu or Placebo

Cohort 3: Shigella Vaccine at 10^10 cfu or Placebo

Cohort 4: Shigella Vaccine or Placebo

Arm Description

3:1 randomization to one dose of vaccine or placebo (Cohort n=8)

3:1 randomization to one dose of vaccine or placebo (Cohort n=8)

3:1 randomization to one dose of vaccine or placebo (Cohort n=8)

2:2:1 randomization to receive either two doses of vaccine, 1 dose of vaccine and one dose of placebo, or two doses of placebo at Days 1 and 29 (Cohort n=30)

Outcomes

Primary Outcome Measures

Number, Proportion, and Severity of Fever, Diarrhea, or Dysentery
The number, proportion, and severity of fever, diarrhea, or dysentery (hemoccult testing will only be performed during the inpatient days) within 7 days of vaccination, for all those receiving vaccine and for each of the vaccine dosages evaluated
Number, Proportion, and Severity of Solicited Local and Systemic Adverse Reactions
The number, proportion, and severity of solicited local and systemic adverse reactions (diarrhea, dysentery, fever, nausea, vomiting, abdominal discomfort, tenesmus, myalgia, arthralgia, and anorexia) within 7 days of vaccination for all those receiving vaccine and for each of the vaccine dosages evaluated
Number, Proportion, Severity, and Relatedness of Non-Serious Unsolicited Adverse Reactions
The number, proportion, severity, and relatedness of non-serious unsolicited adverse reactions within 28 days of vaccination for all those receiving vaccine and for each of the vaccine dosages evaluated
Number, Proportion, and Severity of Clinical Safety Laboratory Adverse Events
The number, proportion, and severity of clinical safety laboratory adverse events from the time of each study vaccination through approximately 7 days after each study vaccination.
Occurrence of SUSARs
The occurrence of SUSARs in the study
Occurrence of all SAEs
The occurrence of all SAEs, regardless of the assessment of relatedness, from the time of the first vaccination through approximately 6 months after the last study vaccination
Geometric Mean Number of Vaccine Organisms
The geometric mean number (and interquartile range) of vaccine organisms, per day and at the peak of shedding, expressed as cfu/mL for each dosage group
Number and Proportion of Sequential Days of Fecal Shedding of Shigella Organisms
The number and proportion of sequential days of fecal shedding of Shigella organisms which are documented to contain the genes expressing ETEC antigens for each dosage group. Genetically stable organisms will be defined as being PCR positive for Shigella (ipaH or virG), CFA/I (cfaB), and LTB (eltB)

Secondary Outcome Measures

Full Information

First Posted
November 11, 2020
Last Updated
October 28, 2022
Sponsor
University of Maryland, Baltimore
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1. Study Identification

Unique Protocol Identification Number
NCT04634513
Brief Title
Shigella CVD 31000: Study of Responses With Shigella-ETEC Vaccine Strain CVD 1208S-122
Official Title
Phase 1 Study of the Safety, Tolerability, and Immunogenicity of Oral Doses of CVD 1208S-122, a Prototype Attenuated Shigella Flexneri 2a Live Vector Expressing Enterotoxigenic Escherichia Coli Antigens
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 29, 2022 (Actual)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The purpose of this study is to determine whether a live, oral, combined Shigella-ETEC vaccine candidate, known as strain CVD 1208S-122, is safe and immunogenic.
Detailed Description
The purpose of this study is to determine whether a live, oral, combined Shigella-ETEC vaccine candidate, known as strain CVD 1208S-122, is safe and immunogenic. This will be a phase 1, double-blind, placebo-controlled, dose-escalating, single-center study, involving three vaccine dosage escalation cohorts (10^8, 10^9, and 10^10 cfu vaccine organisms). Each of the three dose-escalation cohorts will consist of 8 study participants who will be randomly allocated to receive either vaccine (n=6) or placebo (n=2), as a single, oral dose. An independent Safety Monitoring Committee (SMC) will review the available safety data for Cohorts 1 - 3 through 7 days post-vaccination before proceeding to the enrollment of the next cohort. The fourth cohort will be an adaptive design cohort consisting of 30 study participants to be randomly allocated to receive either two doses of vaccine (n=12), one dose of vaccine (n=12), or two doses of placebo (n=6), with the dosage selection based on the highest well-tolerated dose in the dose-escalation cohorts (1 - 3), as determined by the SMC. Each of the dose-escalation cohorts (1 - 3) will receive the oral dose of blinded study product while in the inpatient setting. During the following subsequent 96 hours (4 days), participants will remain on the inpatient research isolation ward to be closely monitored, and each stool will be collected by study staff. The evaluation and monitoring of participants enrolled in the fourth cohort will be conducted entirely in the outpatient setting.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Shigella Infection, Enterotoxigenic Escherichia Coli Infection
Keywords
vaccine, strain CVD 1208S-122

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: Shigella Vaccine at 10^8 cfu or Placebo
Arm Type
Experimental
Arm Description
3:1 randomization to one dose of vaccine or placebo (Cohort n=8)
Arm Title
Cohort 2: Shigella Vaccine at 10^9 cfu or Placebo
Arm Type
Experimental
Arm Description
3:1 randomization to one dose of vaccine or placebo (Cohort n=8)
Arm Title
Cohort 3: Shigella Vaccine at 10^10 cfu or Placebo
Arm Type
Experimental
Arm Description
3:1 randomization to one dose of vaccine or placebo (Cohort n=8)
Arm Title
Cohort 4: Shigella Vaccine or Placebo
Arm Type
Experimental
Arm Description
2:2:1 randomization to receive either two doses of vaccine, 1 dose of vaccine and one dose of placebo, or two doses of placebo at Days 1 and 29 (Cohort n=30)
Intervention Type
Biological
Intervention Name(s)
strain CVD 1208S-122
Intervention Description
Live, attenuated, vaccine strain of S. flexneri 2a expressing CFA/I and LT of enterotoxigenic E. coli
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Sodium bicarbonate buffer
Primary Outcome Measure Information:
Title
Number, Proportion, and Severity of Fever, Diarrhea, or Dysentery
Description
The number, proportion, and severity of fever, diarrhea, or dysentery (hemoccult testing will only be performed during the inpatient days) within 7 days of vaccination, for all those receiving vaccine and for each of the vaccine dosages evaluated
Time Frame
7 days following vaccination
Title
Number, Proportion, and Severity of Solicited Local and Systemic Adverse Reactions
Description
The number, proportion, and severity of solicited local and systemic adverse reactions (diarrhea, dysentery, fever, nausea, vomiting, abdominal discomfort, tenesmus, myalgia, arthralgia, and anorexia) within 7 days of vaccination for all those receiving vaccine and for each of the vaccine dosages evaluated
Time Frame
7 days following vaccination
Title
Number, Proportion, Severity, and Relatedness of Non-Serious Unsolicited Adverse Reactions
Description
The number, proportion, severity, and relatedness of non-serious unsolicited adverse reactions within 28 days of vaccination for all those receiving vaccine and for each of the vaccine dosages evaluated
Time Frame
28 days following vaccination
Title
Number, Proportion, and Severity of Clinical Safety Laboratory Adverse Events
Description
The number, proportion, and severity of clinical safety laboratory adverse events from the time of each study vaccination through approximately 7 days after each study vaccination.
Time Frame
7 days following vaccination
Title
Occurrence of SUSARs
Description
The occurrence of SUSARs in the study
Time Frame
The entire study period (6-7 months)
Title
Occurrence of all SAEs
Description
The occurrence of all SAEs, regardless of the assessment of relatedness, from the time of the first vaccination through approximately 6 months after the last study vaccination
Time Frame
The entire study period (6-7 months)
Title
Geometric Mean Number of Vaccine Organisms
Description
The geometric mean number (and interquartile range) of vaccine organisms, per day and at the peak of shedding, expressed as cfu/mL for each dosage group
Time Frame
for each day of the 7 days following vaccination
Title
Number and Proportion of Sequential Days of Fecal Shedding of Shigella Organisms
Description
The number and proportion of sequential days of fecal shedding of Shigella organisms which are documented to contain the genes expressing ETEC antigens for each dosage group. Genetically stable organisms will be defined as being PCR positive for Shigella (ipaH or virG), CFA/I (cfaB), and LTB (eltB)
Time Frame
for each day of the 7 days following vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female, 18 - 49 years of age Written informed consent provided Determined to be in good health* based on medical history and review of concomitant medications *Good health as defined by an absence of an active chronic medical condition which requires daily prescription medication(s). Participants may be eligible if the medical condition only requires infrequent as needed (PRN) medication and if the investigator determines that the condition does not pose a risk to participant safety or the assessment of reactogenicity and immunogenicity. Any chronic medical condition which does not require a daily prescription medication but might pose a risk to a participant with rapid dehydration (i.e., rapid intravascular volume changes) would be ineligible to participate. Documented acceptable results from screening laboratory work (defined in Appendix B), including: Complete blood count (CBC) with differential for total white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (Hg), platelet count Creatinine, alanine aminotransferase (ALT), total bilirubin Serum Immunoglobulin A (IgA) level Human immunodeficiency virus (HIV) antibody, Hepatitis B surface antigen (HBsAg), Hepatitis C virus antibody (HCV) HLA-B27 histocompatibility testing Serum Beta human chorionic gonadotropin (β-HCG) test, if the participant is a woman of child-bearing potential A passing score (≥70%) on a Comprehension Assessment Tool Agrees not to participate in another clinical trial during the study period Females of child-bearing potential† agree to use an acceptable form of birth control‡ from enrollment and through at least 4 weeks after vaccination †Females of child-bearing potential, defined as having not been sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure® placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or <1 year has passed since the last menses, if menopausal. ‡Acceptable birth control includes barrier methods such as condoms or diaphragms/cervical cap with spermicide; effective intrauterine devices; NuvaRing®; and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill") or alternatively, monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the study vaccination, abstinence from sexual intercourse with a male partner, or sexual relationships with non-male partners. Available for up to a 6-day inpatient stay For Participants of Cohorts 1-3 during the time when a U.S. Public Health Emergency for COVID-19 exists, SARS-CoV-2 testing must be performed upon admission to the inpatient ward and must document a negative test result prior to vaccination. Exclusion Criteria: A positive pregnancy test at screening or within 24 h prior to study product dosing A female who is breastfeeding Poor venous access, as defined by inability to obtain venous blood, for screening labs, after 3 venipuncture attempts Abnormal vital signs, defined as: Systolic BP >150 mmHg or Diastolic BP >90 mmHg Resting heart rate >100 bpm Oral temperature ≥38.0°C Having received prior vaccines for or have had prior infection with ETEC, LT, cholera, or Shigella, within the past 3 years History of diarrhea during travel to a developing country within the past 3 years History of chronic gastrointestinal illness, including severe dyspepsia, lactose intolerance, or another significant gastrointestinal tract disease (e.g., irritable bowel syndrome, inflammatory bowel syndrome, gastric ulcer disease) Regular use (≥once weekly) of laxatives, anti-diarrheal agents, anti-constipation agents, or antacid therapies History of major gastrointestinal surgery (uncomplicated laparoscopic appendectomy or cholecystectomy >1-year prior is permitted) Abnormal bowel habits, as defined by <3 stools per week or >2 stools per day in the past 6 months Use of systemic antimicrobials§ within the past 2 weeks use of topical (skin), otic, or ophthalmic antibiotics is acceptable, if those doses are not expected to result in significant systemic absorption levels Use of oral, parenteral or high-dose inhaled steroids within 30 days Use of any medication which might affect immune function# within 30 days #examples include anti-cancer drugs, immunomodulating monoclonal antibody therapeutics, and rheumatologic therapies Diagnosis of schizophrenia or other major psychiatric disease Alcohol or drug abuse within last 5 years Presence of immunosuppression, which could be due to active neoplastic disease or a history of any hematologic malignancy (excluding resolved non-melanoma skin cancers), radiation therapy, or primary or secondary immunodeficiencies History of allergy to quinolone (e.g., ciprofloxacin) or sulpha drugs (e.g., trimethoprim-sulfamethoxazole) Known history of seizure disorder (remote history of a childhood seizure disorder which has completely resolved is acceptable) Occupation involving the handling of ETEC, cholera, or Shigella bacteria Occupation in food handling industry or care of very young children (<2 years old), elderly (≥70 years), or immunocompromised During the time when a U.S. Public Health Emergency for COVID-19 exists, within 14 days prior to the time of vaccination, the presence of 2 or more of any of the following symptoms: fever (≥38°C, chills, myalgia, headache, sore throat, or new olfactory and taste disorder During the time when a U.S. Public Health Emergency for COVID-19 exists, within 14 days prior to the time of vaccination, the presence of 1 or more of any of the following respiratory symptoms: cough which cannot otherwise be explained, shortness of breath, or difficulty breathing Any other criteria which, in the investigator's opinion, would compromise the safety of the study, the ability of a subject to participate, or the results of the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa Chrisley, RN
Phone
410-706-6156
Email
lchrisle@som.umaryland.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Wilbur Chen, MD, MS
Phone
410-706-6156
Email
wchen@som.umaryland.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wilbur Chen, MD, MS
Organizational Affiliation
Center for Vaccine Development and Global Health, University of Maryland School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Maryland, Baltimore, University of Maryland School of Medicine, Center for Vaccine Development and Global Health
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Connie Thomas, RN
Phone
410-706-6156
Email
constance.thomas@som.umaryland.edu
First Name & Middle Initial & Last Name & Degree
Wilbur Chen, MD, MS
Phone
410-706-6056
Email
wchen@som.umaryland.edu

12. IPD Sharing Statement

Learn more about this trial

Shigella CVD 31000: Study of Responses With Shigella-ETEC Vaccine Strain CVD 1208S-122

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