Study of Efficacy and Safety of ABO809 in Healthy Participants

Phase 1

Completed

• Conditions: Cryptosporidium Infection, Cryptosporidiosis
• Interventions: Biological: Cryptosporidium parvum oocysts (ABO809)

• Registration Number: NCT05036668
• Lead Sponsor: Novartis Pharmaceuticals

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-08-31
• Study First Submitted QC: 2021-08-31
• Study First Posted: 2021-09-05
• Study Start: 2022-04-07
• Primary Completion: 2022-11-07
• Study Completion: 2022-12-27
• Results First Submitted: 2023-11-14
• Status Verified: 2024-06
• Results First Submitted QC: 2024-06-27
• Last Update Submitted: 2024-06-27
• Results First Posted: 2024-10-02
• Last Update Posted: 2024-10-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Demonstrated understanding of Cryptosporidium disease, safety measures and transmission risks
• Good health
• Ability to communicate well with the Investigator

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ABO809	Cryptosporidium parvum oocysts (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

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Cryptosporidium Infection From 72 Hours to 10 Days Post ABO809 Oral Administration	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 Outcome Measures

Name	Time	Method
Percentage of Participants Showing Clinical Diarrheal Illness From Day 1 to Day 28 Post ABO809 Oral Administration	From Day 1 up to Day 28	Clinical diarrheal illness was defined as the occurrence of at least two diarrheal bowel events within 24 hours on at least two days after the administration of ABO809. 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.; Grade 1 stool is defined as formed stool which does not take the shape of the container.; Grade 2 stool is defined as soft stool which does not easily take the shape of the container.; Grade 3 diarrheal stool is defined as thick liquid stool taking the shape of the container.; Grade 4 diarrheal stool is defined as opaque watery stool. Grade 5 diarrheal stool is defined as rice water or clear watery stools.
Number of Diarrhea Stools 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.; Grade 1 stool is defined as formed stool which does not take the shape of the container.; Grade 2 stool is defined as soft stool which does not easily take the shape of the container.; Grade 3 diarrheal stool is defined as thick liquid stool taking the shape of the container.; Grade 4 diarrheal stool is defined as opaque watery stool. Grade 5 diarrheal stool is defined as rice water or clear watery stools.
Overall Diarrheal Stool Weight	From Day 1 up to Day 28	Stool weight in grams of each stool from each participant were 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 were measured during outpatient period from Day 14 to Day 28.
Maximum Stool Grade by Stool Grade Category	From Day 1 up to Day 28	All collected stool samples were 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. The maximum stool grade is the highest stool grade of all episodes in a participant.
Time to Resolution of Clinical Diarrheal Illness	From Day 1 up to Day 28	Clinical diarrheal illness was defined as the occurrence of at least two diarrheal bowel events within 24 hours on at least two days after the administration of ABO809. The time to resolution is the 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 up to Day 28	Percentage of participants with Cryptosporidium infection following an oral administration of ABO809. Cryptosporidium infection were measured by examining the presence of a Cryptosporidium antigen in stool using a commercially available diagnostic Enzyme Immunoassay (EIA) test.
Time to Onset of Clinical Diarrheal Illness	From Day 1 up to Day 28	Clinical diarrheal illness was defined as the occurrence of at least two diarrheal bowel events within 24 hours on at least two days after the administration of ABO809. The time to onset is the number of days until the start diarrheal illness.
Time to Onset of Cryptosporidium Infection	From Day 1 up to Day 10	Time to onset is the number of days until the start of Cryptosporidium infection which were 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 72 hours post-administration 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 Resolution of Cryptosporidium Infection	From Day 1 up to Day 28	Time to resolution is the 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 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.	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 cryptosporidiosis, persistent cryptosporidium shedding, moderate or severe dehydration and non-intestinal sequelae including eye pain or joint pain.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇺🇸 Baltimore, Maryland, United States