An Open Label Cryptosporidium Controlled Human Infection Model (CHIM) to Assess the Efficacy and Safety of ABO809 in Healthy Participants
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Percentage of Participants With Cryptosporidium Infection From 72 Hours to 10 Days Post ABO809 Oral Administration
Study Overview
Brief Summary
The purpose of this Phase I controlled human infection model (CHIM) study was to determine if oral administration of a good manufacturing practice (GMP) supply of Cryptosporidium parvum oocysts (ABO809) to healthy volunteers resulted in a Cryptosporidium infection and diarrheal illness. The study measured fecal oocysts (parasitological endpoint) as well as diarrhea and associated signs and symptoms (clinical endpoint).
Detailed Description
This study was funded by the Wellcome Trust. This Phase 1 Cryptosporidium controlled human infection model (CHIM) study employed 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 were enrolled in cohorts of approximately 10 participants who received ABO809 on the same day (Day 1). The study consisted of three sequential cohorts which were dosed one after the other for a total of 30 participants. A dose level group received the same ABO809 dose and could be comprised of multiple cohorts. The first dose level group started with a cohort of 10 participants who received ABO809 at a dose of 1x10^4 oocysts. The study continued to enroll participants in the same dose level group if the desired incidences of infection and diarrheal illness were observed, up to a total of approximately 30 participants. If the desired incidences of infection and diarrheal illness were not observed, a new dose level group, receiving ABO809 at a dose of 1x10^6 oocysts, could be initiated. If needed to optimize the model, intermediate ABO809 doses could be evaluated.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Other
- Masking
- None
Masking Description
Open-Label
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Arms & Interventions
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
Intervention: Cryptosporidium parvum oocysts (ABO809) (Biological)
Outcomes
Primary Outcomes
Percentage of Participants With Cryptosporidium Infection From 72 Hours to 10 Days Post ABO809 Oral Administration
Time Frame: At ≥72 hours post-administration (or sooner if associated with symptoms suggestive of diarrheal illness) up to Day 10 (inclusive).
Cryptosporidium infection was measured by examining the presence of a Cryptosporidium antigen in stool using a commercially available diagnostic Enzyme Immunoassay (EIA) test. Up to 3 stool samples per day were collected, each separated by approximately 4-hour intervals, were analyzed by EIA for parasitological assessment of oocyst shedding.
Secondary Outcomes
- Percentage of Participants Showing Clinical Diarrheal Illness From Day 1 to Day 28 Post ABO809 Oral Administration(From Day 1 up to Day 28)
- Number of Diarrhea Stools Per Participant(From Day 1 up to Day 28)
- Overall Diarrheal Stool Weight(From Day 1 up to Day 28)
- Maximum Stool Grade by Stool Grade Category(From Day 1 up to Day 28)
- Time to Resolution of Clinical Diarrheal Illness(From Day 1 up to Day 28)
- Percentage of Participants With Characteristics of Clinical Signs and Symptoms Associated With Clinical Diarrheal Illness(From Day 1 up to Day 28)
- Percentage of Participants With Cryptosporidium Infection From 72 Hours to Day 28 Post ABO809 Oral Administration(From 72 hours post-administration up to Day 28)
- Time to Onset of Clinical Diarrheal Illness(From Day 1 up to Day 28)
- Time to Onset of Cryptosporidium Infection(From Day 1 up to Day 10)
- Percentage of Participants With Fecal Shedding of Cryptosporidium Parvum Oocysts(From 72 hours post-administration up to Day 28)
- Time to Resolution of Cryptosporidium Infection(From Day 1 up to Day 28)
- Number of Participants With Adverse Events of Special Interest (AESIs)(Adverse events were reported from oral administration of ABO809 up to a maximum duration of 56 days.)