Study of Efficacy and Safety of ABO809 in Healthy Participants
Study Details
Study Description
Brief Summary
The purpose of this Phase I controlled human infection model (CHIM) study is to determine if oral administration of a good manufacturing practice (GMP) supply of Cryptosporidium parvum oocysts (ABO809) to healthy volunteers results in a Cryptosporidium infection and diarrheal illness. The study will measure fecal oocysts (parasitological endpoint) as well as diarrhea and associated signs and symptoms (clinical endpoint).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This study is funded by the Wellcome Trust. This Phase 1 Cryptosporidium controlled human infection model (CHIM) study employs a single-center, open-label design to characterize the incidence of infection and associated symptoms following the administration of single doses of Cryptosporidium parvum oocysts (CE).
Healthy volunteers will be enrolled in cohorts of approximately 10 participants who will receive ABO809 on the same day (Day 1). The study will consist of three (to a maximum of six) sequential cohorts which will be dosed one after the other for a total of 30 (to a maximum of approximately 60) participants. A dose level group will receive the same ABO809 dose and can be comprised of multiple cohorts. The first dose level group will start with a cohort of 10 participants who will receive ABO809 at a dose of 1x104 oocysts. The study will continue to enroll participants in the same dose level group if the desired incidences of infection and diarrheal illness are observed, up to a total of approximately 30 participants. If the desired incidences of infection and diarrheal illness are not observed, a new dose level group, receiving ABO809 at a dose of 1x106 oocysts, may be initiated. If needed to optimize the model, intermediate ABO809 doses may be evaluated.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ABO809 Participants will receive ABO809 at a single oral dose of 1x10^4 oocysts. Other doses such as 1x10^6 oocysts may be considered to optimize the model |
Biological: Cryptosporidium parvum oocysts (ABO809)
ABO809 3x10^6 CE/3mL concentrate for oral suspension, single dose at Day 1
|
Outcome Measures
Primary Outcome Measures
- Percentage of participants with cryptosporidium infection from 72 hours to 10 Days post ABO809 oral administration [From 72 hours post-administration (or sooner if associated with symptoms suggestive of diarrheal illness) up to Day 10]
Percentage of participants with cryptosporidium infection following an oral administration of ABO809. Cryptosporidium infection will be measured by examining the presence of a Cryptosporidium antigen in stool using a commercially available diagnostic Enzyme Immunoassay (EIA) test.
Secondary Outcome Measures
- Percentage of participants showing clinical diarrheal illness from Day 1 to Day 28 post ABO809 oral administration [From Day 1 up to Day 28]
A participant will be considered as showing clinical diarrheal illness if diarrhea is observed on at least two days during the observation period from Day 1 to Day 28. Resolution of diarrheal illness from Crypotosporidium infection requires ≥2 consecutive days with no diarrheal stools (stool sample grades 1 or 2).
- Number of diarrhea episodes per participant [From Day 1 up to Day 28]
Diarrhea is defined as at least one stool sample grading 3-5 on the Stool Grading system in one day. Grades 1 and 2 are considered normal stool and Grades 3-5 are considered diarrheal stool. Grades 3-5 stools are defined as thick liquid diarrhea taking the shape of the container, opaque watery, rice water or clear watery stools.
- Stool weight [From Day 1 up to Day 28]
Stool weight in grams of each stool from each participant will be measured during inpatient period from Day 1 up to Day 10. Stool weight in grams of stool collected 24 hours prior to outpatient visit from each participant will be measured during outpatient period from Day 14 to Day 28.
- Grading of stool consistency [From Day 1 up to Day 28]
All collected stool samples will be graded according to the Stool Grading system. Grades 1 and 2 are considered normal stool and Grades 3-5 are considered diarrheal stool. Grades 3-5 stools are defined as thick liquid diarrhea taking the shape of the container, opaque watery, rice water or clear watery stools.
- Time to onset of diarrheal illness [From Day 1 up to Day 28]
Number of days until the start diarrheal illness, which is defined as at least 2 diarrheal bowel movements within 24 hours on at least 2 days.
- Time to resolution of diarrheal illness [From Day 1 up to Day 28]
Number of days until the resolution of diarrheal illness, which is defined as 2 or more consecutive days with no diarrheal stools (stool grades 1 or 2).
- Percentage of participants with characteristics of clinical signs and symptoms associated with clinical diarrheal illness [From Day 1 up to Day 28]
Clinical signs and symptoms associated with clinical diarrheal illness such as: abdominal pain, abdominal cramping, nausea, vomiting, fever, electrolyte disbalance, dehydration.
- Percentage of participants with Cryptosporidium infection from 72 hours to Day 28 post ABO809 oral administration [From 72 hours post-administration (or sooner if associated with symptoms suggestive of diarrheal illness) up to Day 28]
Percentage of participants with Cryptosporidium infection following an oral administration of ABO809. Cryptosporidium infection will be measured by examining the presence of a Cryptosporidium antigen in stool using a commercially available diagnostic Enzyme Immunoassay (EIA) test.
- Percentage of participants with fecal shedding of Cryptosporidium parvum oocysts [From Day 1 up to Day 28]
Percentage of participants with fecal shedding of Cryptosporidium parvum oocysts following an oral administration of ABO809. Fecal shedding will be measured by examining the presence of a Cryptosporidium antigen in stool using a commercially available diagnostic Enzyme Immunoassay (EIA) test.
- Time to onset of Cryptosporidium infection [From Day 1 up to Day 28]
Number of days until the start of Cryptosporidium infection which will be measured by examining the presence of a Cryptosporidium antigen in stool using a commercially available diagnostic Enzyme Immunoassay (EIA) test.
- Time to resolution of Cryptosporidium infection [From Day 1 up to Day 28]
Number of days until the resolution of Cryptosporidium infection in participants who developed an infection following an oral administration of ABO809. Resolution of Cryptosporidium infection is defined as no evidence of Cryptosporidium in stool samples collected over ≥2 consecutive days.
- Number of adverse events of special interest (AESIs) by telephone follow-up after Day 28 visit through 12 months post ABO809 oral administration [From Day 28 up to 12 months after ABO809 administration]
The following adverse events associated with Cryptosporidium infection are considered AESIs in this trial: Gastroenteritis in the absence of Cryptosporidium infection, extraintestinal cryptosporidiosis, persistent or recurrent cryptosporidosis, persistent cryptosporidium shedding, moderate or severe dehydration and non-intestinal sequelae including eye pain or joint pain.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Demonstrated understanding of Cryptosporidium disease, safety measures and transmission risks
-
Good health
-
Ability to communicate well with the Investigator
Exclusion Criteria:
- History of Cryptosporidium infection, gastrointestinal conditions (including diarrheal syndromes, gastroenteritis and gastrointestinal tract surgery), immunodeficiency, infections, significant medical concerns, hypersensitivity to nitazoxanide or other specified antibiotics.
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Baltimore | Maryland | United States | 21201 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Principal Investigator: Mohamed Al-Ibrahim, Pharmaron CPC, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CABO809A02101