|
Cryptosporidium controlled human
infection model (CHIM) in healthy adults |
· prospect of benefit
in healthy adults with Cryptosporidium induced diarrhea |
· C. parvum model utilized
for technical reasons, although C. hominis more common human pathogen |
| · informs
dose selection for studies in pediatric patients |
·
needs to be established and validated |
| ·
clinical syndrome, parasitological and clinical end
points under monoinfection condition |
· limited
viability period of GMP oocysts |
| · conducted
in healthy volunteers, mitigates safety confounders |
· monoinfection state may not be clinically relevant to
target pediatric patient population |
| ·
phase 1 settings: faster recruitment and smaller sample
size |
· unknown translatability of efficacy to target
population |
| Adult HIV-positive
cryptosporidiosis patients |
· natural infection
in potential secondary target population |
· confounded
safety and efficacy due to advanced immunocompromised
state |
| · PK in context of
high GI motility |
· presence of other pathogens/coinfections
and/or concurrent
medications |
| · high mortality |
| · operational complexity in the resource poor settings |
| Pediatric cryptosporidiosis patient
population |
· assessment of safety and efficacy
in the target population |
· prospect of clinical
benefit will not have been previously
established |
| · natural course of infection |
· high-risk and vulnerable patient population |
| · with relevant clinical strains |
· uncertainty in predicted efficacious dose in the context
of high GI motility |
| · risk investment
in juvenile toxicity study prior to
phase I to avoid program delays |
| · operational
complexity in the resource poor settings |
