Safety and Efficacy Study of a Vaccine Against Enterotoxigenic Escherichia Coli (ETEC) to Prevent Moderate to Severe Diarrhea
Development of a Polyvalent Vaccine Against Enterotoxigenic Escherichia Coli (ETEC)Protective Efficacy of the Deletion-Attenuated, Multi-valent ACE527 Against Challenge With a Prototype Strain of Enterotoxigenic E.Coli Expressing LT and ST Enterotoxins and CFA/I (Strain H10407) in Human Challenge Model.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Maryland
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Baltimore, Maryland, Forenede Stater, 21205
- Center for Immunization Research (CIR)
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion criteria:
- Male or female age ≥18 and ≤ 50 years.
- General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
- Negative serum pregnancy test before first (visit V0) and before challenge (visit C0) for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female subjects unable to bear children must have this documented (e.g. tubal ligation or hysterectomy) or must have negative pregnancy tests.
- Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
- Completion of a training session and demonstrated comprehension of the protocol procedures, knowledge of ETEC-associated illness, and by passing a written examination.
- Availability for the study duration, including all planned follow-up visits.
Exclusion criteria:
- Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study. Some medical conditions which are adequately treated and stable would not preclude entry into the study. These conditions might include stable asthma controlled with inhalers or mild hypertension stably controlled with a single agent.
- Significant abnormalities in screening hematology, serum chemistry or urinalysis as determined by PI or PI in consultation with the MM and sponsor.
- Presence in the serum of HIV antibody, HBsAg, or HCV antibody.
- Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay).
- Evidence of current excessive alcohol consumption or drug dependence.
- Evidence of impaired immune function.
- BMI <19, >34
- Recent vaccination or receipt of an investigational product (within 30 days before vaccination).
- Intention to donate blood or blood products for one month following the completion of study participation (note: The Red Cross will not allow blood donations for 1 year following participation in an investigational research study).
- Any other criteria which, in the investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study
- Working as a food handler, in child-care or as a healthcare worker with direct patient contact.
- Have household contacts who are <2 years old or >80 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).
- Abnormal stool pattern (fewer than 3 per week or more than 3 per day).
- Regular use of laxatives, antacids, or other agents to lower stomach acidity.
- Use of any medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.
- Known allergy to two of the following antibiotics: quinolones, trimethoprim-sulfamethoxazole, and penicillin.
- Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within two years prior to dosing, OR planned travel to endemic countries during the length of the study.
- Vaccination for or ingestion of ETEC, cholera, or LT toxin within 3 years prior to dosing.
- Use of antibiotics during the 7 days before dosing or proton pump inhibitors, H2 blockers or antacids within 48 hours prior to dosing.
- History of diarrhea in the 7 days prior to vaccination (outpatient diarrhea is defined as ≥ 3 unformed loose stools in 24 hours).
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Forebyggelse
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
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Eksperimentel: ACE527
First cohort: ACE527 vaccine doses of 9 x 10E10 cfu on study day 0 and 21 on an outpatient basis. Second cohort: ACE527 vaccine dose of 9 x 10E10 cfu on study day 0 and 21 on an outpatient basis. |
ACE527 comprises a mixture of three live, attenuated ETEC strains; ACAM2025 (CFA/I+ and LTB+), ACAM2022 (CS5+, CS6+ and LTB+), and ACAM2027 (CS1+, CS2+, CS3+ and LTB+).
The vaccine is administered orally as a two-dose regimen, at 9x1010 cfu, on Days 0 and 21, in 200 ml CeraVacx buffer.
The required volume of each vaccine strain, supplied as a frozen suspension, is mixed into the buffer solution prior to dosing.
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Placebo komparator: Placebo vaccine
First cohort: Placebo vaccine on study day 0 and 21 on an outpatient basis. Second cohort: Placebo vaccine on study day 0 and 21 on an outpatient basis. |
Placebo
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Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Severe diarrhea: ≥6 grade 3-5 stools in 24 hrs, or >800g of grade 3-5 stools in 24 hrs and moderate diarrhea: 4-5 grade 3-5 stools in 24 hrs or 401-800g of grade 3-5 stools in 24 hrs
Tidsramme: Study Day 49 to 57
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Study Day 49 to 57
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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Number of subjects with severe diarrhea (if any)
Tidsramme: Study Day 49 to 57
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Study Day 49 to 57
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Number of subjects with diarrhea of any severity
Tidsramme: Study Day 49 to 57
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Study Day 49 to 57
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Mean total weight of grade 3-5 stools passed per subject
Tidsramme: Study Day 49 to 57
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Study Day 49 to 57
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Mean number of grade 3-5 stools per subject
Tidsramme: Study day 49 to 57
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Study day 49 to 57
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Number of subjects with nausea, vomiting, anorexia, or abdominal pain/cramps rated as moderate to severe.
Tidsramme: Study Day 0 to 77
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Study Day 0 to 77
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Number of subjects who indicate they would have reduced their daily activity if they had been vacationing or traveling for business because of their ETEC illness.
Tidsramme: Last visit
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Last visit
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Mean time to onset of diarrhea.
Tidsramme: Study Day 49 to 57
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Study Day 49 to 57
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Number of subjects with moderate to severe ETEC illness
Tidsramme: Study Day 49 to 57
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Study Day 49 to 57
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Number of colony forming unite (cfu) of the challenge strain per gram of stool
Tidsramme: Study day 49 to 57
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Study day 49 to 57
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Number of subjects requiring early antibiotic treatment
Tidsramme: Study Day 49 to 57
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Study Day 49 to 57
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Number of subjects requiring IV fluids
Tidsramme: Study Day 49 to 57
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Study Day 49 to 57
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Systemic immune responses to the constituent strains of the vaccine
Tidsramme: Selected Time Points
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Selected Time Points
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Mucosal immune responses to the constituent strains of the vaccine
Tidsramme: Selected Time Points
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Selected Time Points
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The intestinal colonization by the three individual vaccine strains and challenge strain post-vaccination
Tidsramme: Selected Time Points
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Selected Time Points
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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Samarbejdspartnere
Samarbejdspartnere
Efterforskere
Efterforskere
- Ledende efterforsker: Clayton Harro, MD, CIR, Johns Hopkins School of Public Health
Datoer for undersøgelser
Studer store datoer
Studiestart
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Faktiske)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- ACE527-102
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