Study to Examine the Effects of Oral Fenretinide
NCT Number: NCT06528457
Acronym: PROTECT
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Dengue
Interventions: DRUG: ISLA101|DRUG: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)|OTHER: Placebo
Sponsor: Island Pharmaceuticals
Sex: ALL
Age: ADULT
Enrollment: 14
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-10
Completion Date: 2025-08
Locations: SUNY Upstate Medical University, East Syracuse, New York, 13057, United States

Summary:
This randomized, placebo controlled single center study examines the extent to which 600 mg/m2/day of orally administered ISLA101 (fenretinide), given prophylactically or therapeutically, may reduce or eliminate signs and symptoms of dengue virus (DENV) infection over 29 days following subcutaneous challenge of healthy subjects with 'Dengue 1 Live Virus Human Challenge' (DENV-1-LVHC). Humoral and cellular immune responses, both innate and adaptive, circulating virus, and changes in clinical laboratory measures will also be examined.

Primary Outcome Measures: Number of participants without warning signs of dengue, Frequency, intensity and duration of dengue without warning signs defined as fever, nausea, vomiting, rash, aches and pains, or leukopenia., over 29 days from inoculation|Number of participants with warning signs of dengue, Frequency, intensity and duration of dengue with warning signs defined as Abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation (ascites, pleural effusion), mucosal bleeding, lethargy, restlessness, liver enlargement \>2 cm, laboratory: increase in hematocrit concurrent with rapid decrease in platelet count., over 29 days from inoculation|Number of participants with clinical signs and symptoms of severe dengue, Frequency, intensity and duration of severe dengue defined as severe plasma leakage, severe hemorrhage, severe organ impairment., over 29 days from inoculation
Secondary Outcome Measures: To characterize circulating virus in the two interventional groups versus control, For each group compared with controls:

* Blood samples will be obtained for measurement of levels of viremia using qualitative and/or quantitative reverse transcription-polymerase chain reaction (RT PCR)., over 29 days from inoculation|To characterize circulating virus in the two interventional groups versus control, For each group compared with controls:

* Saliva samples will be obtained for measurement of levels of viremia using qualitative and/or quantitative RT PCR., over 29 days from inoculation|To evaluate changes from baseline in hematocrit among the three groups, Number of participants with abnormal hematocrit results, observed over 29 days from inoculation, will be summarized overall, by group, by duration and by toxicity grade for each group compared with control. A summary of subjects with shifts from baseline (relative to normal range) in laboratory test results will be provided., Over 29 days from inoculation|To evaluate changes from baseline in platelet among the three groups, Number of participants with abnormal platelet counts, observed over 29 days from inoculation, will be summarized overall, by group, by duration and by toxicity grade for each group compared with control. A summary of subjects with shifts from baseline (relative to normal range) in laboratory test results will be provided., Over 29 days from inoculation|To describe the Cmax of ISLA101 at the tested dose, route, and duration, Concentration-time plots of first and NEXT-TO-LAST dose of ISLA101, from first to next to last dose of ISLA101 (Day 24) for Cohort 1|To describe the Tmax of ISLA101 at the tested dose, route, and duration, Concentration-time plots of first and NEXT-TO-LAST dose of ISLA101, from first to next to last dose of ISLA101 (Day 24) for Cohort 1|To describe the Cmax of ISLA101 at the tested dose, route, and duration, Concentration-time plots of first and NEXT-TO-LAST dose of ISLA101, from first to next to last dose of ISLA101 (Day 21) for Cohort 2|To describe the Tmax of ISLA101 at the tested dose, route, and duration, Concentration-time plots of first and NEXT-TO-LAST dose of ISLA101, from first to next to last dose of ISLA101 (Day 21) for Cohort 2
Other Outcome Measures: To identify changes in viral genome, Whole genome DENV nucleotide sequence analyses from all subjects who become DENV infected in both the active and control groups., over 29 days from inoculation|To examine immune responses to DENV-1-LVHC among the three groups, For each group compared with controls:

a. Changes from baseline in anti-DENV-1 antibody levels and biological activity in serum and saliva (isotype specific), over 29 days from inoculation|To examine subject HLA haplotypes, HLA haplotype determination, over 29 days from inoculation|Number of participants with treatment emergent adverse events of ISLA101 in healthy subjects infected with DENV-1-LVHC, Unsolicited AEs with a focus on SAEs and SUSARs, over 29 days from inoculation|Number of participants with adverse events related to dengue in healthy subjects infected with DENV-1-LVHC, Solicited AEs with a focus on SAEs and SUSARs, over 29 days from inoculation