- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT01060748
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.
Panoramica dello studio
Descrizione dettagliata
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Maryland
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Baltimore, Maryland, Stati Uniti, 21205
- Center for Immunization Research (CIR)
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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).
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Prevenzione
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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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Comparatore placebo: 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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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
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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
Lasso di tempo: Study Day 49 to 57
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Study Day 49 to 57
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Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
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Number of subjects with severe diarrhea (if any)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: Last visit
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Last visit
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Mean time to onset of diarrhea.
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: Study Day 49 to 57
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Study Day 49 to 57
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Number of subjects requiring IV fluids
Lasso di tempo: 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
Lasso di tempo: Selected Time Points
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Selected Time Points
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Mucosal immune responses to the constituent strains of the vaccine
Lasso di tempo: 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
Lasso di tempo: Selected Time Points
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Selected Time Points
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Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Clayton Harro, MD, CIR, Johns Hopkins School of Public Health
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- ACE527-102
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