ShigellaPhase 2NCT00866476
Safety and Efficacy Study of CVD 1208S, a Live, Attenuated Oral Vaccine to Prevent Shigella Infection: Phase IIa
A Phase 2 study testing CVD 1208S, a Shigella flexneri 2a live, oral vaccine in people with Shigella, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
The purpose of this study is to determine whether CVD 1208S (a live, attenuated, oral vaccine) is safe and effective in the prevention of Shigella infection. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Shigella
- What is being tested?
- CVD 1208S, a Shigella flexneri 2a live, oral vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Feb 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18 to 45 years, inclusive
- Good general health as determined by a screening evaluation within 45 days before inoculation
- Expressed interest and availability to fulfill study requirements
- Informed, written consent
- Agrees to indefinite storage of unused clinical specimens at the CVD for use in future research, which may require separate IRB approval
- Agrees not to participate in another investigational vaccine or drug trial during the 8-month study
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- Has no childbearing potential, i.e., either surgically sterilized or 1 year postmenopausal, or agrees to abstain from becoming pregnant from the day of screening (at least 14 days before vaccination) through Day 98 of the trial by using one of the following methods of birth control:
- Abstinence;
- Intrauterine contraceptive device;
- Oral contraceptives or equivalent hormonal contraception, e.g., progestogen-only; implantable, cutaneous hormonal patch, injectable contraceptives, or Nuvaring (vaginal hormonal ring);
- Diaphragm in combination with contraceptive jelly, cream, or foam;
- Condoms with spermicide.
- Agrees not to donate blood to a blood bank for 12 months after receiving the vaccine
Who cannot join
- An acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses. This includes, but is not limited to:
- Chronic liver disease, renal insufficiency, unstable or progressive neurological disorders, diabetes mellitus, collagen vascular disease (such as lupus), active neoplastic disease (not cured or in remission), or previous hematological malignancy
- Repeated (two or more) seizures occurring after 5 years of age, and not related to a concussion
- Any of the following in the past 10 years: Crohn's disease, ulcerative colitis, irritable bowel disease, celiac disease, stomach or intestinal ulcers, or 2 or more episodes of arthritis (joint pain and swelling);
- Recurrent infections (greater than 1 hospitalization for invasive bacterial infections, e.g., pneumonia, meningitis);
- G6PD deficiency;
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- Any current illness requiring daily medication (vitamins, birth control pills, nasal or topical medications, allowed);
- Blood in stool on more than 2 occasions (other than small amounts from straining) in past 12 months;
- Recurrent diarrhea (greater than 5 episodes in past 6 months, each lasting 3 days or more).
- Immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months
- Long term (greater than 2 weeks) use of oral or parenteral steroids, or high-dose inhaled steroids (greater than 800 micrograms/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (Nasal and topical steroids are allowed)
- History of the following types of abdominal surgery:
- Any major gastrointestinal surgery (e.g., intestinal resection or splenectomy);
- A laparotomy for any reason (e.g., hysterectomy, Caesarian section, appendectomy, or herniorrhaphy) within the last 3 years;
- Laparoscopic abdominal surgery within the past year.
- Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
- Known allergy or intolerance to ciprofloxacin, trimethoprim/sulfamethoxazole (or other sulfa antibiotic), ampicillin (for women), or corn
- History of shigellosis or Shigella vaccination or challenge or a laboratory worker with known exposure to Shigella
- Anticipates any of the following during the first 84 days (12 weeks) of the study:
- Shares a household with a child less than 3 years of age, a pregnant woman or a woman who plans to become pregnant during this time;
- Household or sexual contact with someone who has weakened immunity (such as someone with HIV infection, someone receiving treatment for cancer, or an elderly person greater than 70 years);
- Occupation as a food-handler, childcare (for children less than 3 years), or health care worker with direct patient contact
- Poor peripheral access for placement of an intravenous line
- A clinically significant abnormality on physical examination, including, but not limited to:
- A pathologic heart murmur
- Lymphadenopathy
- Hypertension (systolic blood pressure greater than 150 or diastolic blood pressure greater than 90 on 2 separate days during medical screening)
- A large abdominal scar of unclear origin
- Any of the following laboratory abnormalities detected during medical screening:
- WBC less than 3.0 x 103/mm3
- Neutrophils less than 1500/mm3
- Hemoglobin less than 12.0 g/dL (men) or less than 11.0 g/dL (women)
- Platelets less than 130,000/mm3
- Serum sodium less than 130 mEq/L
- Serum creatinine greater than 1.5 mg/dL
- SGPT greater than 82 U/L (men) or greater than 60 (women)
- Fasting glucose greater than 99 mg/dl (if screening greater than 99 mg/dl)
- Positive serology for syphilis, hepatitis C or HIV antibody or hepatitis B surface antigen
- HLA B27 positive
- Stool culture positive for Salmonella, Shigella, Campylobacter, Yersinia, Vibrio cholerae, or lacking normal flora, or pathogenic protozoa by microscopic examination.
- Positive pregnancy test during medical screening or within 24 hours of inoculation or current breast feeding (women)
- Failure to attain a score of at least 70 percent on the written examination (two attempts permitted)
- During the past 3 years, developed diarrhea during travel to a developing country, or within 1 week of returning home
- Receipt of any of the following:
- Any vaccine or investigational drug within 30 days of study vaccine
- A live, attenuated vaccine within the 30 days of the study vaccine
- A subunit or killed vaccine within the 14 days of the study vaccine
- A blood product, including immunoglobulin, in the 90 days before the study vaccine
- Receipt of antibiotics within 7 days of inoculation (or within 21 days if the antibiotic was azithromycin).
- Loose stools (grade 3-5) or any other acute illness such as fever greater than or equal to 100.0 degrees F during the 48 hours before vaccination
- Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant or would render the subject unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland, Baltimore Center for Vaccine Development
Baltimore, Maryland, 21201
About this study
Official title: Safety, Immunogenicity, and Efficacy Following Experimental Challenge of CVD 1208S, a Delta guaBA, Delta Sen, Delta Set Shigella Flexneri 2a Live, Oral Vaccine: Phase IIa Vaccination Study
The purpose of this study is to determine whether CVD 1208S (a live, attenuated, oral vaccine) is safe and effective in the prevention of Shigella infection.
Read the detailed description
The study comprises a Phase 2 vaccination study and a Phase 2b challenge study. The primary objectives of the Phase 2 vaccination study are: 1. To evaluate, in healthy volunteers, the safety and clinical acceptability of three spaced doses (one month apart) of an investigational, live, oral, attenuated vaccine called CVD 1208S, with particular attention to the occurence of diarrhea, dysentery, and fever, and 2. To characterize immune responses following ingestion of this vaccine. The primary objective of the Phase 2b challenge study is to measure the protective efficacy of 3 spaced doses of vaccine after ingestion of an oral challenge strain called Shigella flexneri 2a strain 2457T.
Shigella is a leading cause of disease and death among children younger than 5 years living in developing countries. The difficulty controlling this infection has led experts to believe that prevention with the use of a vaccine is a promising strategy. At the CVD, we have pursued an approach of developing an oral, attenuated Shigella vaccine that prevents infection with the Shigella types of greatest clinical and epidemiologic importance. One of the strains to be included in the vaccine is called Shigella flexneri 2a. Investigators at the CVD have created a vaccine from Shigella flexneri 2a, designated CVD 1208S, using molecular biology techniques. To date, nearly 40 subjects have received varying doses of this vaccine with good clinical tolerance and modest immunogenicity. Previously a single dose of vaccine was used. In the current study, we will administer doses of vaccine on days 0, 28, and 56 to attempt to maximize immunogenicity. Approximately one month after the 3rd dose, a group of ~15-20 vaccinated volunteers along with a similar number of unvaccinated control subjects will be admitted to the CVD Research Isolation Ward at SNBL and challenged with wild type Shigella flexneri 2a. By comparing the attack rate of illness in vaccinated vs. unvaccinated subjects, we will determine the vaccine's ability to confer protective immunity.
- Conditions
- Shigella
- Being tested
- CVD 1208S, a Shigella flexneri 2a live, oral vaccine, Placebo
- Keywords
- Shigella, Vaccine, Mucosal immunity
- Medical subject headings
- Dysentery, Bacillary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CVD 1208S, a Shigella flexneri 2a live, oral vaccineBiological
CVD 1208S consists of freshly harvested ∆guaBA, ∆sen, ∆set S. flexneri 2a strain 2457T suspended in phosphate buffered saline to reach the desired inoculum Form: liquid Dose: 10 to the 9th power CFU in 1.0 ml Route: oral.
PlaceboOther
30 ml of buffer solution (2.0 grams of NaHCO3 dissolved in 150 ml of sterile water) without bacteria, to which food grade corn starch, USP is added, as necessary, to match the turbidity of the vaccine inoculum
| Study group | Role | What they receive |
|---|---|---|
| Vaccine-recipients | Experimental | Not described Receives: Biological: CVD 1208S, a Shigella flexneri 2a live, oral vaccine |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate, in healthy volunteers, the safety and clinical acceptability of three spaced doses (one month apart) of CVD 1208S vaccine candidate, with particular attention to the occurrence of diarrhea, dysentery, and fever
Measured: approximately June 2009-January 2010 and October 2010
To characterize the following immune responses following ingestion of this vaccine: Serum IgA and IgG anti-S. flexneri 2a lipopolysaccharide (LPS) antibody and IgA anti-LPS antibody secreting cells (ASC)
Measured: approximately June 2009, February 2010 - April 2010, and October 2010
Secondary outcomes (2)
To assess the fecal shedding of CVD 1208S
Measured: approximately June - July 2009 and October 2010
To elucidate the systemic and mucosal immune responses to vaccination, including fecal IgA antibodies to LPS and Ipas, IgG anti-LPS ASCs, IgG and IgA Ipa ASC, ASC & T cell homing, specific B and T memory responses, and cytokine production by PBMC.
Measured: approximately June 2009 and August - October 2010
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2009 (estimated)
- Study startJan 2010
- Primary completionFeb 2010
- Study completionFeb 2010
Why it stopped: Reactogenicity met study halting criteria
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ShigellaStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- PATH
- Responsible party
- Principal investigator, Karen Kotloff, University of Maryland, Baltimore
- Investigators
- Karen L Kotloff, M.D., Principal investigator, University of Maryland, Baltimore Center for Vaccine Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00866476
- Sponsor's protocol ID
- HP-00040710 Phase IIa
- Other IDs
- Shigella CVD 27000
- Status last verified
- Apr 2021
- First submitted
- 19 Mar 2009
- Last updated
- 29 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Immunogenicity, and Efficacy Following Experimental Challenge of CVD 1208S, a Delta guaBA, Delta Sen, Delta Set Shigella Flexneri 2a Live, Oral Vaccine: Phase IIa Vaccination Study
- ClinicalTrials.gov ID
- NCT00866476
- Acronym / sponsor ID
- HP-00040710 Phase IIa
- Conditions
- Shigella
- Keywords
- Shigella, Vaccine, Mucosal immunity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Reactogenicity met study halting criteria
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- PATH
- Study start
- Jan 2010
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 20 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether CVD 1208S (a live, attenuated, oral vaccine) is safe and effective in the prevention of Shigella infection.
Detailed description
The study comprises a Phase 2 vaccination study and a Phase 2b challenge study. The primary objectives of the Phase 2 vaccination study are: 1. To evaluate, in healthy volunteers, the safety and clinical acceptability of three spaced doses (one month apart) of an investigational, live, oral, attenuated vaccine called CVD 1208S, with particular attention to the occurence of diarrhea, dysentery, and fever, and 2. To characterize immune responses following ingestion of this vaccine. The primary objective of the Phase 2b challenge study is to measure the protective efficacy of 3 spaced doses of vaccine after ingestion of an oral challenge strain called Shigella flexneri 2a strain 2457T.
Shigella is a leading cause of disease and death among children younger than 5 years living in developing countries. The difficulty controlling this infection has led experts to believe that prevention with the use of a vaccine is a promising strategy. At the CVD, we have pursued an approach of developing an oral, attenuated Shigella vaccine that prevents infection with the Shigella types of greatest clinical and epidemiologic importance. One of the strains to be included in the vaccine is called Shigella flexneri 2a. Investigators at the CVD have created a vaccine from Shigella flexneri 2a, designated CVD 1208S, using molecular biology techniques. To date, nearly 40 subjects have received varying doses of this vaccine with good clinical tolerance and modest immunogenicity. Previously a single dose of vaccine was used. In the current study, we will administer doses of vaccine on days 0, 28, and 56 to attempt to maximize immunogenicity. Approximately one month after the 3rd dose, a group of ~15-20 vaccinated volunteers along with a similar number of unvaccinated control subjects will be admitted to the CVD Research Isolation Ward at SNBL and challenged with wild type Shigella flexneri 2a. By comparing the attack rate of illness in vaccinated vs. unvaccinated subjects, we will determine the vaccine's ability to confer protective immunity.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vaccine-recipients | Experimental | Biological: CVD 1208S, a Shigella flexneri 2a live, oral vaccine |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Age 18 to 45 years, inclusive
- Good general health as determined by a screening evaluation within 45 days before inoculation
- Expressed interest and availability to fulfill study requirements
- Informed, written consent
- Agrees to indefinite storage of unused clinical specimens at the CVD for use in future research, which may require separate IRB approval
Key exclusion criteria (51 listed)
- An acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses. This includes, but is not limited to:
- Immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months
- Long term (greater than 2 weeks) use of oral or parenteral steroids, or high-dose inhaled steroids (greater than 800 micrograms/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (Nasal and topical steroids are allowed)
- History of the following types of abdominal surgery:
- Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CVD 1208S, a Shigella flexneri 2a live, oral vaccineCVD 1208S consists of freshly harvested ∆guaBA, ∆sen, ∆set S. flexneri 2a strain 2457T suspended in phosphate buffered saline to reach the desired inoculum Form: liquid Dose: 10 to the 9th power CFU in 1.0 ml Route: oral. | Biological | Vaccine-recipients |
| Placebo30 ml of buffer solution (2.0 grams of NaHCO3 dissolved in 150 ml of sterile water) without bacteria, to which food grade corn starch, USP is added, as necessary, to match the turbidity of the vaccine inoculum | Other | Placebo |
Primary outcome
To evaluate, in healthy volunteers, the safety and clinical acceptability of three spaced doses (one month apart) of CVD 1208S vaccine candidate, with particular attention to the occurrence of diarrhea, dysentery, and fever
Time frame: approximately June 2009-January 2010 and October 2010
To characterize the following immune responses following ingestion of this vaccine: Serum IgA and IgG anti-S. flexneri 2a lipopolysaccharide (LPS) antibody and IgA anti-LPS antibody secreting cells (ASC)
Time frame: approximately June 2009, February 2010 - April 2010, and October 2010
2 secondary outcomes
To assess the fecal shedding of CVD 1208S
Time frame: approximately June - July 2009 and October 2010
To elucidate the systemic and mucosal immune responses to vaccination, including fecal IgA antibodies to LPS and Ipas, IgG anti-LPS ASCs, IgG and IgA Ipa ASC, ASC & T cell homing, specific B and T memory responses, and cytokine production by PBMC.
Time frame: approximately June 2009 and August - October 2010
Results and safety
The study was stopped early (reason given: Reactogenicity met study halting criteria). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen L Kotloff, M.D. principal investigator
University of Maryland, Baltimore Center for Vaccine Development
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CVD 1208S, a Shigella flexneri 2a live, oral vaccine in people with Shigella, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 51 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Reactogenicity met study halting criteria). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate, in healthy volunteers, the safety and clinical acceptability of three spaced doses (one month apart) of CVD 1208S vaccine candidate, with particular attention to the occurrence of diarrhea, dysentery, and fever (time frame: approximately June 2009-January 2010 and October 2010). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2021.