A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-5366 in Healthy Participants and Participants Seropositive for HSV-2 With Recurrent Genital Herpes

A Phase 1a/1b, Blinded, Placebo-Controlled Study of the Safety, Tolerability and Pharmacokinetics of Single- and Multiple-Ascending Doses of ABI-5366 in Healthy Subjects and in Subjects Who Are Seropositive for Herpes Simplex Virus Type 2 With Recurrent Genital Herpes

This study is designed to assess safety, tolerability, and pharmacokinetics (PK) of single ascending dose (SAD) of ABI-5366 in Part A in healthy participants and multiple-ascending doses (MAD) of ABI-5366 in Part B in participants seropositive for Herpes Simplex Virus Type 2 (HSV-2) with recurrent genital herpes. Effect of food will also be evaluated in Part A.

Study Overview

• Status: Completed
• Conditions: Recurrent Genital Herpes Simplex Type 2
• Intervention / Treatment: Drug: ABI-5366; Drug: ABI-5366 Placebo

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • East Sydney Doctors
    • Miranda, New South Wales, Australia, 2228
      • Canopy Clinical Sutherland
    • Sydney, New South Wales, Australia, 2010
      • Momentum Clinical Research
    • Sydney, New South Wales, Australia, 2100
      • Canopy Beaches Clinical Research
    • Wollongong, New South Wales, Australia, 2500
      • Canopy Clinical Wollongong
  • Victoria
    • Melbourne, Victoria, Australia, 3021
      • Momentum Sunshine
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research
  • Christchurch, New Zealand, 8011
    • New Zealand Clinical Research Christchurch
  • Hamilton, New Zealand, 3200
    • Pacific Clinical Research Network - Hamilton
  • Nelson, New Zealand, 7011
    • Pacific Clinical Research Network - Tasman
  • Palmerston North, New Zealand, 4414
    • Momentum Palmerston North
  • Rotorua, New Zealand, 3010
    • Pacific Clinical Research Network - Rotorua
  • Upper Hutt, New Zealand, 5018
    • Pacific Clinical Research Network - Wellington
  • Waikanae, New Zealand, 5036
    • Momentum Kapiti

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Part A: Inclusion Criteria:

• Subject has a body mass index (BMI) between ≥ 18.0 and < 32.0 kg/m2
• In good health (as determined by the Investigator) based on medical history, physical examination, ECG, and clinical laboratory results.
• Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day -1 or Day 1 (predose)
• Agreement to comply with protocol-specified contraceptive requirements

Part B: Inclusion Criteria:

• Subject has a body mass index (BMI) between ≥ 18.0 and < 32.0 kg/m2
• Other than HSV infection, is in good health (as determined by the Investigator) based on medical history, physical examination, ECG, and clinical laboratory results.
• Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1 (predose)
• Agreement to comply with protocol-specified contraceptive requirements

Part A and B: Exclusion Criteria:

• Current infection of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), acute hepatitis A virus (HAV), or acute hepatitis E virus (HEV).
• History of any illness that, in the opinion of the Investigator, might confound the results of the study, pose an additional risk in administering study drug to the subject, or a condition known to interfere with the absorption/distribution/elimination of drugs.
• History of any significant drug-related allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, urticaria, or multiple drug allergies
• History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening
• Has participated in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 half-lives before Screening, whichever is longer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: SAD Cohorts 1-5, ABI-5366; Single dose of ABI-5366 (tablet) in Part A for Cohorts 1-5	Drug: ABI-5366; Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD); Drug: ABI-5366 Placebo; Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD)
Placebo Comparator: Part A: SAD Cohorts 1-5, Placebo; Single dose of matching placebo (tablet) in Part A for Cohorts 1-5	Drug: ABI-5366; Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD); Drug: ABI-5366 Placebo; Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD)
Experimental: Part A: SAD Fed Cohort 6, ABI-5366; Single dose of ABI-5366 (tablet) in Part A for Cohort 6, food effect	Drug: ABI-5366; Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD)
Experimental: Part B: MAD Cohorts 1-4 ABI-5366; Weekly or monthly dose of ABI-5366 (tablet) in Part B for Cohorts 1-4. May have a loading dose.	Drug: ABI-5366; Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD); Drug: ABI-5366 Placebo; Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD)
Placebo Comparator: Part B: MAD Cohorts 1-4 Placebo; Weekly or monthly dose of matching placebo (tablet) in Part B for Cohorts 1-4. May have a loading dose.	Drug: ABI-5366; Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD); Drug: ABI-5366 Placebo; Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration Time Curve (AUC) of ABI-5366	SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Maximum Observed Plasma Concentration (Cmax) of ABI-5366	SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Time to Cmax (Tmax) of ABI-5366	SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Apparent Terminal Elimination Half Life (t 1/2) of ABI-5366	SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Apparent Systemic Clearance (CL/F) of ABI-5366	SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Apparent Volume of Distribution (Vz/F) of ABI-5366	SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Dose normalized AUCs and Cmax of ABI-5366	SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Proportion of subjects with adverse events (AEs), premature treatment discontinuation due to AEs, and abnormal laboratory results	Up to 98 days after last dose

Secondary Outcome Measures

Outcome Measure	Time Frame
SAD Cohorts: Comparison of plasma AUC and Cmax between fasted and fed treatments	SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing.
MAD Cohorts: If applicable, comparison of plasma PK profiles and parameters with and without loading doses	MAD Cohorts: At pre-specified time points from Days 8 to 36.
MAD Cohorts: Difference in viral shedding rate (number of anogenital swabs positive for HSV-2 DNA/total number of swabs) across treatments	MAD Cohorts: At pre-specified time points from Days 8 to 36.
MAD Cohorts: Difference in mean and median HSV-2 DNA copies/mL for swab samples positive for HSV-2 DNA across treatments	MAD Cohorts: At pre-specified time points from Days 8 to 36.
MAD Cohorts: Difference in the proportion of swab samples with HSV-2 DNA >4 log10 copies/mL across treatments (number of swabbing samples with HSV-2 DNA >4 log10 copies/mL / total number of swabs obtained)	MAD Cohorts: At pre-specified time points from Days 8 to 36.
MAD Cohorts: Difference in number of shedding episodes during the swabbing period across treatments	MAD Cohorts: At pre-specified time points from Days 8 to 36.
MAD Cohorts: Difference in duration of shedding episodes during the swabbing period across treatments	MAD Cohorts: At pre-specified time points from Days 8 to 36.
MAD Cohorts: Difference in subclinical shedding rate (number of swabs positive for HSV-2 DNA in the absence of lesions/total number of swabs in the absence of lesions) across treatments	MAD Cohorts: At pre-specified time points from Days 8 to 36.
MAD Cohorts: Difference in lesion rate during the swabbing period across treatments	MAD Cohorts: At pre-specified time points from Days 8 to 36.
MAD Cohorts: Difference in lesion duration during the swabbing period across treatments	MAD Cohorts: At pre-specified time points from Days 8 to 36.
MAD Cohorts: Difference in recurrence rate (number of reappearances of lesions during the swabbing period/total days assessed) across treatments	MAD Cohorts: At pre-specified time points from Days 8 to 36.

Collaborators and Investigators

• Sponsor: Assembly Biosciences
• Investigators: Principal Investigator: Edward Gane, New Zealand Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2024
• Primary Completion (Actual): February 3, 2026
• Study Completion (Actual): February 3, 2026

Study Registration Dates

• First Submitted: April 18, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: PK; Healthy Participants; HSV-2; Recurrent Genital Herpes; ABI-5366
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Virus Diseases; Genital Diseases, Female; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Herpesviridae Infections; Herpes Simplex; Herpes Genitalis
• Other Study ID Numbers: ABI-5366-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No