통제된 인간 감염 모델에서 IMM-124E(Travelan®)의 효능을 평가하기 위한 임상 연구

활성 비교기: Travelan

IMM-124E (Travelan) is the investigational product. Travelan 1200mg will be taken orally once daily for 7 days.

생물학적: Travelan

Travelan tablets (1200mg) administered orally once daily for 7 days

다른 이름들:

• IMM-124E

위약 비교기: Placebo

ProMilk 85 milk powder is the placebo. Placebo has been manufactured into tablets using the same manufacturing process as Travelan. The same dosing schedule of 1200mg will be taken orally once-daily for 7 days.

다른: Placebo

Placebo (1200mg) tablets administered orally once daily for 7 days

다른 이름들:

• ProMilk 85 분유

Protective Efficacy of a Single Daily Dose of Travelan Against Moderate-to-severe Diarrhea Following Challenge With Enterotoxigenic E. Coli (ETEC) Strain H10407.

The number of subjects who encounter moderate to severe diarrhea (defined as ≥4 Grade 3-5 stools in any 24-hour period post-challenge or ≥401 grams of Grade 3-5 stools in the 5-day period post-challenge) will be recorded for the Travelan group and the placebo group.

All stool samples will be collected, weighed and graded.

Stool grading scale:

Grade 1 = Fully formed (normal) Grade 2 = Soft (normal) Grade 3 = Thick liquid (diarrheal) Grade 4 = Opaque watery (diarrheal) Grade 5 = Rice-water (diarrheal).

Diarrhea (Grade 3-5 stools) severity in a 24 hour period (1g = 1ml):

1-mild (2-3 loose/liquid stool totaling <400 g), 2-moderate (4 to 5 loose/liquid stools or >401 to 800 g), 3-severe (6 or more loose/liquid stools totaling >800 g).

Number of Subjects With Severe Diarrhea Post ETEC Challenge

Severe diarrhea defined as 6 or more loose liquid stools in a 24 hour period totaling >800g. (1g = 1ml).

All stools will be collected, weighed (1g = 1ml) and graded.

Stool Grading Scale:

Grade 1 = Fully formed (normal) Grade 2 = Soft (normal) Grade 3 = Thick liquid (diarrheal) Grade 4 = Opaque watery (diarrheal) Grade 5 = Rice-water (diarrheal).

Diarrhea severity (Grade 3-5 stools) in a 24 hour period post-challenge (1g = 1ml):

1-mild (2-3 loose/liquid stool totaling <400 g), 2-moderate (4 to 5 loose/liquid stools or >401 to 800 g), 3-severe (6 or more loose/liquid stools totaling >800 g).

Subjects With Diarrhea of Any Severity

The number of subjects who encounter diarrhea of any severity post challenge will be recorded for the Travelan group and the placebo group.

All stool samples will be collected, weighed and graded.

Stool grading scale:

Grade 1 = Fully formed (normal) Grade 2 = Soft (normal) Grade 3 = Thick liquid (diarrheal) Grade 4 = Opaque watery (diarrheal) Grade 5 = Rice-water (diarrheal).

Diarrhea (Grade 3-5 stools) severity in a 24 hour period (1g = 1ml):

1-mild (2-3 loose/liquid stool totaling <400 g), 2-moderate (4 to 5 loose/liquid stools or >401 to 800 g), 3-severe (6 or more loose/liquid stools totaling >800 g).

Subjects Requiring Oral Rehydration Solution and/or Intravenous Fluids Post ETEC Challenge for the Travelan Group and the Placebo Group

Measurement of the number of subjects who require oral rehydration solution and/or intravenous fluids on one or more days post challenge.

Subjects Requiring Early Antibiotic Treatment

Early antibiotic treatment commenced when any of the follow criteria were met and a physician determined it was warranted:

1. Severe diarrhea (Grade 3-5 stools) based on volume (>800g in 24 hrs)
2. Diarrhea of any severity AND 2 or more of the following symptoms classified as severe (CTCAE v5.0, Grade 3) abdominal pain, abdominal cramps, nausea, arthralgia, fever >38oC.
3. Any fever >39oC
4. Subjects who experienced unexpected severe events such as symptomatic hypotension disproportionate to volume loss, renal dysfunction or altered mental state at the discretion of the investigators
5. A study physician determines that early treatment is warranted for other reasons

Number of Participants With AEs Graded as Moderate-to-severe (Grade 2-4) for Diarrhea, Fever, Vomiting and Other Listed AEs as Assessed Using the CTCAE v5.0 Criteria for AEs.

All AEs will be recorded for the Travelan group and the placebo group using the following criteria (1-4):

1. Diarrhea severity (Grade 3-5 stools) in a 24 hour period (1g = 1ml):1-mild (2-3 loose/liquid stool totaling <400 g), 2-moderate (4 to 5 loose/liquid stools or >401 to 800 g), 3-severe (6 or more loose/liquid stools totaling >800 g).
2. Temperature maximum measured in a 24 hr period: no fever (<38.0°C), 1-mild (38.0-38.4°C), 2-moderate (38.5-38.9°C), 3-severe (>39.0°C); 4-Potentially life threatening (>40oC).
3. Vomiting in a 24 hr period: 0-no episodes, 1-mild (1-2 episodes), 2-moderate (2-3 episodes), or 3-severe (>5 episodes).
4. Nausea, abdominal discomfort and pain, abdominal cramps, headache, malaise or anorexia graded as follows: 0-Non-existent, 1 -mild (not interfering with routine activities), 2 -moderate (interfering but not precluding routine activities), 3 -severe (precluding routine activities), 4 - potentially life threatening (requires hospitalization)