Development of a Phase 1 Cryptosporidiosis Controlled Human Challenge Model in Healthy Volunteers Using Current Good Manufacturing Practice Cryptosporidium Parvum Oocysts and Conducted Under an Investigational New Drug Application.
Source: PubMed, NCBI / U.S. National Library of Medicine
Cryptosporidiosis is a leading cause of pediatric diarrhea in low-resource settings with limited treatment options. We established a controlled human infection model (CHIM) using current good manufacturing practice (CGMP)-compliant Cryptosporidium parvum oocysts (ABO809) under an investigational new drug application to expedite evaluation of new anti-Cryptosporidium therapies. In this phase 1 trial, healthy adult volunteers received a single oral high dose (1 × 104 or 1 × 106 viable oocysts) of ABO809. The primary end point was incidence of Cryptosporidium infection and secondary objectives included characterization of clinical symptoms and safety of ABO809. Nitazoxanide was provided as rescue medication. Of the 27 evaluable participants challenged with ABO809, 15 (57%) had Cryptosporidium infection, diagnosed by enzyme immunoassay and 19-20 (70%-74%) had infection confirmed by stool quantitative polymerase chain reaction analysis. Median onset and duration of Cryptosporidium infection was 4 and 6 days respectively. Overall, 70% of participants had diarrhea (stool grade 3-5), with a median onset at 3 days. Individuals with severe clinical cryptosporidiosis symptoms tended to shed more oocysts, indicating a correlation between symptom severity and fecal oocyst shedding. Adverse events, including expected cryptosporidiosis-related gastrointestinal and nongastrointestinal symptoms, were observed in all participants, without any other serious adverse events or fatalitie
Abstract
Cryptosporidiosis is a leading cause of pediatric diarrhea in low-resource settings with limited treatment options. We established a controlled human infection model (CHIM) using current good manufacturing practice (CGMP)-compliant Cryptosporidium parvum oocysts (ABO809) under an investigational new drug application to expedite evaluation of new anti-Cryptosporidium therapies. In this phase 1 trial, healthy adult volunteers received a single oral high dose (1 × 104 or 1 × 106 viable oocysts) of ABO809. The primary end point was incidence of Cryptosporidium infection and secondary objectives included characterization of clinical symptoms and safety of ABO809. Nitazoxanide was provided as rescue medication. Of the 27 evaluable participants challenged with ABO809, 15 (57%) had Cryptosporidium infection, diagnosed by enzyme immunoassay and 19-20 (70%-74%) had infection confirmed by stool quantitative polymerase chain reaction analysis. Median onset and duration of Cryptosporidium infection was 4 and 6 days respectively. Overall, 70% of participants had diarrhea (stool grade 3-5), with a median onset at 3 days. Individuals with severe clinical cryptosporidiosis symptoms tended to shed more oocysts, indicating a correlation between symptom severity and fecal oocyst shedding. Adverse events, including expected cryptosporidiosis-related gastrointestinal and nongastrointestinal symptoms, were observed in all participants, without any other serious adverse events or fatalities. The Cryptosporidium CHIM, developed using CGMP-compliant oocysts, reliably induced infection and symptoms, providing a robust monoinfection model for evaluating new therapeutics and vaccines. NCT05036668.