EDP-323 for Respiratory Syncytial Virus

Overseen By Chris Harris

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Enanta Pharmaceuticals, Inc

Must not be taking: Tobacco, Alcohol, others

Disqualifiers: Pregnancy, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Varies depending on study part

48 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, since the study involves assessing the effect of certain drugs on EDP-323, it's possible that some medications might need to be paused. Please consult with the trial coordinators for specific guidance.

Is EDP-323 safe for humans?

EDP-938, which is similar to EDP-323, has been tested in humans and showed that it is quickly absorbed and generally well-tolerated with few significant side effects when taken in doses up to 600 mg/day. This suggests that EDP-323 may also be safe, but more specific data on EDP-323 would be needed to confirm this. ^{1 2 3 4 5}

How is the drug EDP-323 different from other treatments for respiratory syncytial virus (RSV)?

EDP-323 is unique because it targets the nucleoprotein of the RSV, which is a different approach compared to traditional fusion inhibitors that prevent the virus from entering cells. This mechanism may offer a higher barrier to resistance and potentially more effective treatment options for RSV. ^{3 4 5 6 7}

What is the purpose of this trial?

The primary aim of the study is to assess the effect of itraconazole, carbamazepine, quinidine, and fluconazole individually on the pharmacokinetics and safety of EDP-323 in healthy adult participants. Each participant's duration in the study will be dependent upon which study part they are enrolled.

Research Team

Enanta Pharmaceuticals, Inc

Principal Investigator

Enanta Pharmaceuticals, Inc

Eligibility Criteria

This trial is for healthy adults who can participate in a study to understand how certain drugs affect the body's handling and safety of EDP-323, which is being investigated for Respiratory Syncytial Virus. Specific eligibility criteria are not provided.

Inclusion Criteria

I will use two effective birth control methods during and 30 days after the trial.

I am a man who will use contraception during and up to 90 days after the study.

An informed consent document signed and dated by the subject

Exclusion Criteria

Participation in a clinical trial within 28 days prior to the first dose of study drug

Current tobacco smokers or use of tobacco within 3 months prior to Screening

I haven't had a fever or active infection in the last 7 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EDP-323 in combination with either itraconazole, carbamazepine, quinidine, or fluconazole on respective dosing days

Varies depending on study part

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• EDP-323

Trial Overview The study investigates how itraconazole, carbamazepine, quinidine, and fluconazole each alter the pharmacokinetics (how the body processes) and safety of EDP-323 when taken by healthy individuals.

Participant Groups

Group I: EDP-323 and quinidine interaction (Part 3) Experimental Treatment 2 Interventions

Subjects will receive EDP-323 and quinidine on respective dosing days

Group II: EDP-323 and itraconazole interaction (Part 1) Experimental Treatment 2 Interventions

Subjects will receive EDP-323 and itraconazole on respective dosing days

Group III: EDP-323 and fluconazole interaction (Part 4) Experimental Treatment 2 Interventions

Subjects will receive EDP-323 and fluconazole on respective dosing days

Group IV: EDP-323 and carbamazepine interaction (Part 2) Experimental Treatment 2 Interventions

Subjects will receive EDP-323 and carbamazepine on respective dosing days

Who Is Running the Clinical Trial?

Enanta Pharmaceuticals, Inc

Lead Sponsor

Trials

42

Recruited

3,200+

Findings from Research

In a trial involving 43 infants at risk for RSV, the monoclonal antibody SB 209763 showed a good safety profile with only a few adverse events related to the drug, indicating it is generally safe for use in this population.

While SB 209763 demonstrated some ability to increase neutralization and fusion inhibition titers, it did not significantly reduce the incidence of RSV infections compared to placebo, suggesting that higher doses may be needed for effective protection against RSV lower respiratory tract disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of an intramuscular monoclonal antibody (SB 209763) against respiratory syncytial virus (RSV) in infants and young children at risk for severe RSV disease. Meissner, HC., Groothuis, JR., Rodriguez, WJ., et al.[2020]

The study found that the current AAP guidelines for administering palivizumab, a medication for RSV prophylaxis, may not adequately prioritize infants at the highest risk for hospitalization due to RSV, as some higher-risk infants receive fewer injections than lower-risk infants.

There are discrepancies between the AAP guidelines and existing literature regarding the risk of hospitalization for RSV based on gestational age and severity of lung disease, suggesting that the guidelines need to be revised to better align with the actual risk levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for palivizumab prophylaxis: are they based on infant's risk of hospitalization for respiratory syncytial viral disease? Elhassan, NO., Stevens, TP., Sorbero, ME., et al.[2015]

EDP-938 is a promising new antiviral drug that effectively inhibits respiratory syncytial virus (RSV) replication, showing strong activity against various RSV strains with low effective concentrations (EC50s) in human bronchial epithelial cells.

It works by targeting a specific step in the viral life cycle and has a higher barrier to resistance compared to other antiviral drugs, making it a potentially robust treatment option, as demonstrated by its efficacy in a non-human primate model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EDP-938, a novel nucleoprotein inhibitor of respiratory syncytial virus, demonstrates potent antiviral activities in vitro and in a non-human primate model. Rhodin, MHJ., McAllister, NV., Castillo, J., et al.[2021]

EDP-938, a second-generation antiviral drug for respiratory syncytial virus (RSV), has shown high efficacy in reducing viral load in the lower respiratory tract during early human trials.

The drug is rapidly absorbed after oral administration, with a half-life of 11-18 hours, and administration of up to 600 mg/day for seven days resulted in minimal significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EDP-938, a new antiviral with inhibitory activity against the nucleoprotein of the respiratory syncytial virus]. Reina, J., Iglesias, C.[2023]

In a phase 2a trial involving 178 participants, EDP-938 significantly reduced RSV viral load and total symptom scores compared to placebo, indicating its efficacy as a treatment for RSV infection.

All dosing regimens of EDP-938 demonstrated a safety profile similar to placebo, suggesting that it is a safe option for treating RSV without major side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge. Ahmad, A., Eze, K., Noulin, N., et al.[2023]

Two novel compounds, P13 and C15, were identified as effective inhibitors of human respiratory syncytial virus (RSV) in HEp-2 cell cultures, with IC₅₀ values of 0.11 and 0.13 μM, respectively, indicating strong antiviral activity.

Both compounds require presence during virus entry and cell-to-cell transmission to inhibit RSV, but they do not kill the virus directly or prevent its attachment, and their use can lead to the rapid emergence of drug-resistant viral variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two novel fusion inhibitors of human respiratory syncytial virus. Lundin, A., Bergström, T., Bendrioua, L., et al.[2010]

In a study involving 69 participants, the fusion inhibitor JNJ-53718678 significantly reduced RSV viral load and clinical symptoms compared to placebo, indicating its potential as an effective treatment for RSV infection.

All doses of JNJ-53718678 (75 mg, 200 mg, and 500 mg) demonstrated a reduction in the duration of viral shedding and overall symptom severity, although some participants experienced mild adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiviral Activity of Oral JNJ-53718678 in Healthy Adult Volunteers Challenged With Respiratory Syncytial Virus: A Placebo-Controlled Study. Stevens, M., Rusch, S., DeVincenzo, J., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of an intramuscular monoclonal antibody (SB 209763) against respiratory syncytial virus (RSV) in infants and young children at risk for severe RSV disease. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Guidelines for palivizumab prophylaxis: are they based on infant's risk of hospitalization for respiratory syncytial viral disease? [2015]

3. United States pubmed.ncbi.nlm.nih.gov

EDP-938, a novel nucleoprotein inhibitor of respiratory syncytial virus, demonstrates potent antiviral activities in vitro and in a non-human primate model. [2021]

4. Spain pubmed.ncbi.nlm.nih.gov

[EDP-938, a new antiviral with inhibitory activity against the nucleoprotein of the respiratory syncytial virus]. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Two novel fusion inhibitors of human respiratory syncytial virus. [2010]

7. United States pubmed.ncbi.nlm.nih.gov

Antiviral Activity of Oral JNJ-53718678 in Healthy Adult Volunteers Challenged With Respiratory Syncytial Virus: A Placebo-Controlled Study. [2019]