Norovirus
Conditions
Keywords
tolerability, viral challenge model, antiviral
Brief summary
Participants in this study will be given either CDI-988 or placebo orally before receiving a norovirus challenge virus and continuing for 5 days. Participants will not know whether they are getting placebo or CDI-988. The study will evaluate how well CDI-988 compared to placebo can reduce the incidence of clinical symptoms after a challenge with norovirus. The amount of virus in stool samples will be measured over time. Side effects and pharmacokinetics (the amount of CDI-988 in blood) will also be measured.
Detailed description
This is a single center Phase 1b randomized, double-blind, placebo-controlled study. The primary objective will be to evaluate the efficacy of CDI-988 in comparison to placebo in reducing the incidence of clinical symptoms after challenge with norovirus. Secondary objectives will be to evaluate the efficacy of CDI-988 in comparison to placebo in reducing viral shedding and disease severity and to evaluate the safety of CDI-988 in comparison to placebo.
Interventions
DRUGCDI-988
Antiviral to treat norovirus
DRUGPlacebo
Matching placebo
OTHERSnow Mountain Virus
Challenge with Snow Mountain Virus
Sponsors
Cocrystal Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or non-pregnant female * Aged 18 to 49 years * Good state of health * Known fucosyl transferase 2 (FUT2) secretor status
Exclusion criteria
* History of participation in any norovirus challenge or vaccine clinical trial * Receipt or planned receipt of any non-live vaccines within 7 days or live vaccines within 30 days before screening or prior to Day 28 * History of suspected norovirus gastroenteritis or chronic/recurrent gastrointestinal symptoms (e.g., diarrhea or vomiting) within 2 years prior to screening * History of diagnosed gastrointestinal malabsorption disorders, major gastrointestinal surgery, or diagnosed chronic GI conditions * Presence of moderate or severe illness, fever (≥38°C), or diarrhea/vomiting within 7 days prior to challenge * Any acute illness on Day 1 (dosing day) * Positive Day 0 stool tests for enteric pathogens * Body weight \<45 kg or BMI \<18 or \>32 kg/m² on Day 0 * Use of immunosuppressive therapy within 6 months prior to Day 0 or having any primary or secondary immunocompromising condition * Use of high-dose systemic corticosteroids (≥20 mg/day prednisolone for ≥2 weeks) or high-dose inhaled steroids for \>7 days within 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of norovirus-confirmed disease | Day 0 to Day 21 | Disease is defined as diarrhea and/or vomiting (during the inpatient period), with laboratory-confirmed infection (with SMV specific primers on stool/emesis) or seroconversion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Vesikari Score (MVS) symptom scores during the inpatient period in infected patients | Day 1 to Day 6 | Score based on duration of diarrhea, maximum number of stools in a 24 hour period, duration of vomiting and maximum number of vomiting episodes in a 24 hour period |
| Time to symptom improvement | Day 1 to Day 6 | From peak Total Symptom Score to point where Total Symptom Score is within 3 points of baseline prior to challenge. The Modified Vesikari Score is a clinical tool used to assess the severity of acute gastroenteritis in children. The minimum and maximum values are 0 and 20, respectively. Higher scores mean a worse clinical severity. For example, a higher score reflects more severe symptoms such as longer duration or higher frequency of diarrhea or vomiting. |
| Time to first SMV-negative stool | Day 1 to Day 6 | Determined by RT-qPCR |
| Area Under the Curve of SMV load | Day 1 to Day 21 | Determined by RT-qPCR |
| Incidence of treatment emergent adverse events | Day 0 to Day 21 | Number of participants with adverse events following first dose |
| Incidence of serious adverse events | From signing informed consent to Day 21 | Number of participants with serious adverse events |
| Maximum plasma concentration of CDI-988 | Day 0 and Day 4 pre-dose and at 2, 3, 4, 6, 8, and 12 hours | Amount of CDI-988 in the blood |
| Time of maximum plasma concentration of CDI-988 | Day 0 and Day 4 pre-dose and at 2, 3, 4, 6, 8, and 12 hours | time to reach maximum plasma concentration |
| Area under the plasma concentration time curve | Day 0 and Day 4 pre-dose and at 2, 3, 4, 6, 8, and 12 hours | Measurement of area under the plasma concentration-time curve (AUC) |
Countries
United States
Contacts
CONTACTDavid Huang, MD, PhD
PRINCIPAL_INVESTIGATORNadine Rouphael, MD
Hope Clinic of the Emory Vaccine Center
Outcome results
None listed