Study to Examine the Effects of Oral Fenretinide

NCT06528457 | Completed Phase 2 FDA Drug

• 1 other identifier: ISLA101-P02-CT002
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Dengue

Keywords

dengue; Dengue with Warning Signs; Dengue Without Warning Signs

Outcome Measures

Primary Outcomes (1)

• Characterization of DENV viremia following inoculation

  Area under the curve of RNAemia by qRT-PCR for Cohort 1 Time to loss of detection of dengue virus RNAemia for Cohort 2

  over 29 days from inoculation

Secondary Outcomes (15)

• To further characterize circulating virus in the two interventional groups versus control

  over 29 days from inoculation

• To characterize circulating virus in the two interventional groups versus control

  over 29 days from inoculation

• To characterize circulating virus in the two interventional groups versus control

  Over 29 days from inoculation

• To characterize circulating virus in the two interventional groups versus control

  Over 29 days from inoculation

• To characterize circulating virus in the two interventional groups versus control

  Over 29 days from inoculation

Study Arms (4)

Cohort A

EXPERIMENTAL

The first cohort (Cohort A) allows examination of prophylaxis as well as treatment, as ISLA101 will be taken prior to inoculation and for 21 days thereafter. Subjects will be randomized 3:1 (active:control), enrolling in a single group three days prior to inoculation. Following the morning dose on the 4th day of dosing, all subjects will be administered 0.5 mL DENV-1-LVHC (6.5 x 103 PFU/mL).

Drug: ISLA101; Drug: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)

Cohort B

PLACEBO COMPARATOR

The first cohort (Cohort B) allows examination of prophylaxis as well as treatment, as placebo will be taken prior to inoculation and for 21 days thereafter. Subjects will be randomized 3:1 (active:control), enrolling in a single group three days prior to inoculation. Following the morning dose on the 4th day of dosing, all subjects will be administered 0.5 mL DENV-1-LVHC (6.5 x 103 PFU/mL).

Drug: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC); Other: Placebo

Cohort C

EXPERIMENTAL

The second cohort (Cohort C) is planned to enroll in two groups of five subjects each, using 4:1 randomization (active:control). All subjects will be administered 0.5 mL DENV-1-LVHC (6.5 x 103 PFU/mL) on Day 1. After the inoculation, subjects will be evaluated in the clinic daily through day 18 (eighteen consecutive daily clinic visits). Dosing with ISLA101 will commence on the morning of Day 8 and continue with a total of 28 doses taken twice daily through Day 21.

Drug: ISLA101; Drug: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)

Cohort D

PLACEBO COMPARATOR

The second cohort (Cohort D) is planned to enroll in two groups of five subjects each, using 4:1 randomization (active:control). All subjects will be administered 0.5 mL DENV-1-LVHC (6.5 x 103 PFU/mL) on Day 1. After the inoculation, subjects will be evaluated in the clinic daily through day 18 (eighteen consecutive daily clinic visits). Dosing with placebo will commence on the morning of Day 8 and continue with a total of 28 doses taken twice daily through Day 21.

Drug: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC); Other: Placebo

Interventions

ISLA101 DRUG

ISLA101 is an oral gelatin capsule containing 100 mg of fenretinide (N-\[4-Hydroxyphenyl\]retinamide, mw 391.56) dissolved in corn oil and polysorbate 80. ISLA101 capsules will be administered orally as one dose of 300 mg/m2 each 12 hours (q12 +/-1 h).

Also known as: fenretinide

Cohort A; Cohort C

Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) DRUG

The DENV-1-LVHC investigational challenge material consists of the dengue-1 virus strain 45AZ5 as a powder, lyophilized for reconstitution. The product is reconstituted with 0.7 mL of water for injection (WFI) and diluted to a concentration of 6.5 x 103 PFU/mL.

Cohort A; Cohort B; Cohort C; Cohort D

Placebo OTHER

Placebo capsules will be administered orally as one dose of 300 mg/m2 each 12 hours (q12 +/-1 h).

Cohort B; Cohort D

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects not of childbearing potential who are 18 years to 55 years of age (inclusive) at the time of consent
• Females not of childbearing potential as defined in the following criteria:
• History of hysterectomy
• Post-menopausal:
• i. Natural post-menopausal females with at least 12 months from natural spontaneous amenorrhea and a serum follicle-stimulating hormone (FSH) concentration ≥ 40 IU/L ii. Post-surgical females must have undergone bilateral oophorectomy at least 6 weeks prior to study
• Male subjects with female partners of childbearing potential must agree to practice abstinence or use a combination of 2 of the following acceptable birth control methods during the study and for at least 90 days after dosing:
• Partners with an intrauterine device (IUD) in place for at least 3 months
• Barrier method (condom or diaphragm) for at least 14 days prior to screening
• Partners using stable hormonal contraceptive for at least 3 months prior to the study
• History of vasectomy at least 3 months prior to signing the Informed Consent Form
• Ability and willingness to sign informed consent
• Passing score on comprehension test of at least 75%, with up to 3 attempts
• Available for the study period
• Provide consent for release of medical records from primary care physician, college or university, urgent care or emergency room visit

You may not qualify if:

• Known or suspected pregnancy (confirmed via a positive serum human chorionic gonadotropin (hCG) pregnancy test at screening), planned pregnancy during the study period, nursing, or lactation
• Men who intend to father a child or donate sperm during the study period, and for 90 days after dosing with study drug
• Any disorders of coagulation
• Any current malignancy other than non-melanoma skin cancer
• Men who intend to father a child during the study period (approximately 120 days)
• Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B (assessed by HBsAg) virus, or suspicion of active influenza virus infection
• Positive antibodies to dengue virus
• Any history of dengue infection or dengue vaccination (licensed or experimental); or planned dengue vaccination during the study period
• Recent (in the past 4 weeks) travel to any dengue endemic area or travel to a country with risk of Yellow Fever or Japanese encephalitis transmission
• Positive urine screen for cocaine, amphetamines, opiates or methadone
• Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
• Active diabetes, active peptic ulcer disease (PUD), chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD)
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunomodulation therapy such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Use of drugs listed in §6.6 that inhibit or induce Cytochrome P450 3A4 (CYP 3A4) enzymes within 30 days prior to administration of study drug and for the duration of Subject participation
• Current, or a history of, auto-immune disease other than well controlled Hashimoto's thyroiditis

Sponsors & Collaborators

• Island Pharmaceuticals: lead

Study Sites (1)

SUNY Upstate Medical University

East Syracuse, New York, 13057, United States

Location

MeSH Terms

Conditions

Dengue

Interventions

Fenretinide

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Study Officials

• Bert Slade, MD

  CCRS

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This double-blinded study is designed to examine two potential uses of ISLA101, the first being prophylaxis against infection and the second being treatment of established infection.

Study Record Dates

• First Submitted: July 15, 2024
• First Posted: July 30, 2024
• Study Start: September 5, 2024
• Primary Completion: May 21, 2025
• Study Completion: July 21, 2025
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)