AzTrials
AzTrials

DenguePhase 2PROTECTNCT06528457

Study to Examine the Effects of Oral Fenretinide

A Phase 2 study testing ISLA101 and Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) in people with Dengue, run by Island Pharmaceuticals at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Dengue
What is being tested?
ISLA101 and Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
15 participants
Where
1 siteUnited States
Study dates
5 Sep 2024to 21 Jul 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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:
  • 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:
Show all 14Show fewer
  • 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

Who cannot join

  • 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
Show all 31Show fewer
  • 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
  • History of Guillain-Barré syndrome
  • Diagnosis with Bipolar Disorder or Schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition, which in the opinion of the investigator prevents the Subject from participating in the study
  • Hives, shortness of breath, swelling of the lips or throat, or hospitalization related to a previous vaccination or an allergy to specific medications/animals for which antigens may be in the virus preparations to include: shellfish allergy, fetal bovine serum, L-glutamine, neomycin and streptomycin
  • Chronic migraine headaches, defined as more than 15 headache days per month over a 3-month period of which more than 8 are migraines, in the absence of medication over use
  • Planning to donate blood in the 1 year following inoculation with dengue
  • Recent blood donation within prior 14 days of inoculation
  • Receipt of blood products or antibodies within 56 days of inoculation or during the study period
  • Planned travel during the study period (~120 days) which would interfere with the ability to complete all study visits
  • Any laboratory abnormalities prior to inoculation for the tests specified in the protocol, that are considered by the investigator to be clinically significant except those listed in exclusion criteria #25
  • subjects with the following grade 2 or greater lab abnormalities: Creatinine; Liver Function Tests - alanine transaminase (ALT), aspartate aminotransferase (AST); Hemoglobin (females and males); white blood count (WBC) decrease; Platelets decreased; prothrombin time (PT); partial thromboplastin time (PTT); Fibrinogen decrease
  • Significant screening physical examination abnormalities at the discretion of the investigator
  • Participation (active or follow-up phase) or planned participation in another vaccine, drug, medical device, or medical procedure clinical trial in the 4 weeks prior to this trial or during the trial.
  • Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation
  • Beliefs that restrict the administration of blood products or transfusions
  • Chronic medical condition that, in the opinion of the investigator, impacts Subject safety
  • Physician discretion

Trial locations and contacts

1 site in 1 country.

United States1 site

  • SUNY Upstate Medical University

    East Syracuse, New York, 13057

Other trials in United States

About this study

Official title: A Phase 2, Randomized, Double Blind, Placebo-Controlled Study to Examine the Prophylactic and Treatment Effects of a Single Dose Level of Oral Fenretinide in a Dengue Virus Challenge Model

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.

Read the detailed description

Pharmacology studies have identified the potential for fenretinide to inhibit the binding of the DENV nonstructural protein 5 (NS5) to host nuclear importins (IMPs) IMP-α and IMP-β1, thereby impairing infection and replication. This Phase 2 study is to evaluate the effectiveness of fenretinide in an encapsulated oral formulation (ISLA101) against challenge with Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) product, both prophylactically and therapeutically. Oral doses will be taken with a high fat meal to improve absorption, as fenretinide is known to have poor gut permeability attributed to its accumulation in lipophilic cell membranes.

Conditions
Dengue
Being tested
ISLA101, Dengue 1 Live Virus Human Challenge (DENV-1-LVHC), Placebo
Keywords
dengue, Dengue with Warning Signs, Dengue Without Warning Signs
Medical subject headings
Dengue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ISLA101Drug

    Also called fenretinide

    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).

  • 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.

  • PlaceboOther

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

Study groups in NCT06528457
Study groupRoleWhat they receive
Cohort AExperimentalThe 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).
Receives: Drug: ISLA101; Drug: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)
Cohort BPlacebo comparatorThe 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).
Receives: Drug: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC); Other: Placebo
Cohort CExperimentalThe 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.
Receives: Drug: ISLA101; Drug: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)
Cohort DPlacebo comparatorThe 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.
Receives: Drug: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC); Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: over 29 days from inoculation

Secondary outcomes (15)

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

    Time to positive RNAemia by qRT-PCR

    Measured: over 29 days from inoculation

  2. To characterize circulating virus in the two interventional groups versus control

    Peak level of RNAemia by qRT-PCR

    Measured: over 29 days from inoculation

  3. To characterize circulating virus in the two interventional groups versus control

    Duration of RNAemia by qRT-PCR (Cohort 1)

    Measured: Over 29 days from inoculation

  4. To characterize circulating virus in the two interventional groups versus control

    Area under the curve of RNAemia by qRT-PCR (Cohort 2)

    Measured: Over 29 days from inoculation

  5. To characterize circulating virus in the two interventional groups versus control

    Levels of infectious virus in blood by Plaque Assay

    Measured: Over 29 days from inoculation

  6. To determine the effect of ISLA101 on solicited signs and symptoms of DENV when given prophylactically and through Day 21 post-inoculation, or only as delayed therapy

    The calculated score of solicited signs and symptoms associated with dengue virus infection, including any of the listed events below, will consist of summing the CTCAE grades across all days for all events, where the score will be summarized by number of positive subjects:

    • Fever, nausea, vomiting, fatigue, rash, abdominal pain, eye pain, bone pain, joint pain, muscle pain, headache.

    Measured: Over 29 days from inoculation

  7. To compare the occurrence of unanticipated signs or symptoms of severe dengue

    The proportion of subjects with any of the following:

    • diffuse abdominal pain or tenderness,
    • persistent vomiting,
    • clinical fluid accumulation (ascites, pleural effusion),
    • mucosal bleeding,
    • lethargy,
    • restlessness,
    • liver enlargement >2 cm,
    • increase in hematocrit concurrent with rapid decrease in platelet count.
    • severe plasma leakage,
    • severe hemorrhage,
    • severe organ impairment.

    Measured: Over 29 days from inoculation

  8. To compare the need for hospital care between groups

    Proportion of subjects hospitalized for dengue symptoms

    Measured: Over 29 days from inoculation

  9. To compare the need for hospital care between groups

    Length of hospitalization stay for dengue symptoms

    Measured: Over 29 days from inoculation

  10. To compare the need for hospital care between groups

    Number of days in the intensive care unit for each hospitalization for dengue symptoms

    Measured: Over 29 days from inoculation

  11. 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.

    Measured: Over 29 days from inoculation

  12. 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

    Measured: from first to next to last dose of ISLA101 (Day 24) for Cohort 1

  13. 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

    Measured: from first to next to last dose of ISLA101 (Day 24) for Cohort 1

  14. 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

    Measured: from first to next to last dose of ISLA101 (Day 21) for Cohort 2

  15. 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

    Measured: from first to next to last dose of ISLA101 (Day 21) for Cohort 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2024
  2. Study start5 Sep 2024
  3. Primary completion21 May 2025
  4. Study completion21 Jul 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06528457
Sponsor's protocol ID
ISLA101-P02-CT002
Acronym
PROTECT
Status last verified
Oct 2025
First submitted
15 Jul 2024
Last updated
24 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ISLA101 and Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) in people with Dengue, run by Island Pharmaceuticals at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Characterization of DENV viremia following inoculation (time frame: over 29 days from inoculation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06528457.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in