Clinical trial NCT06385327: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Recurrent Genital Herpes Simplex Type 2
Keywords: ABI-5366
PK
Healthy Participants
HSV-2
Recurrent Genital Herpes
Lead sponsor: Assembly Biosciences
Sponsor class: INDUSTRY
First posted: 2024-04-26
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Plasma Concentration Time Curve (AUC) of ABI-5366
timeFrame: 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.
measure: Maximum Observed Plasma Concentration (Cmax) of ABI-5366
timeFrame: 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.
measure: Time to Cmax (Tmax) of ABI-5366
timeFrame: 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.
measure: Apparent Terminal Elimination Half Life (t 1/2) of ABI-5366
timeFrame: 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.
measure: Apparent Systemic Clearance (CL/F) of ABI-5366
timeFrame: 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.
measure: Apparent Volume of Distribution (Vz/F) of ABI-5366
timeFrame: 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.
measure: Dose normalized AUCs and Cmax of ABI-5366
timeFrame: 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.
measure: Proportion of subjects with adverse events (AEs), premature treatment discontinuation due to AEs, and abnormal laboratory results
timeFrame: Up to 98 days after last dose
Secondary outcomes:
measure: SAD Cohorts: Comparison of plasma AUC and Cmax between fasted and fed treatments
timeFrame: SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing.
measure: MAD Cohorts: If applicable, comparison of plasma PK profiles and parameters with and without loading doses
timeFrame: MAD Cohorts: At pre-specified time points from Days 8 to 36.
measure: MAD Cohorts: Difference in viral shedding rate (number of anogenital swabs positive for HSV-2 DNA/total number of swabs) across treatments
timeFrame: MAD Cohorts: At pre-specified time points from Days 8 to 36.
measure: MAD Cohorts: Difference in mean and median HSV-2 DNA copies/mL for swab samples positive for HSV-2 DNA across treatments
timeFrame: MAD Cohorts: At pre-specified time points from Days 8 to 36.
measure: 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)
timeFrame: MAD Cohorts: At pre-specified time points from Days 8 to 36.
measure: MAD Cohorts: Difference in number of shedding episodes during the swabbing period across treatments
timeFrame: MAD Cohorts: At pre-specified time points from Days 8 to 36.
measure: MAD Cohorts: Difference in duration of shedding episodes during the swabbing period across treatments
timeFrame: MAD Cohorts: At pre-specified time points from Days 8 to 36.
measure: 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
timeFrame: MAD Cohorts: At pre-specified time points from Days 8 to 36.
measure: MAD Cohorts: Difference in lesion rate during the swabbing period across treatments
timeFrame: MAD Cohorts: At pre-specified time points from Days 8 to 36.
measure: MAD Cohorts: Difference in lesion duration during the swabbing period across treatments
timeFrame: MAD Cohorts: At pre-specified time points from Days 8 to 36.
measure: MAD Cohorts: Difference in recurrence rate (number of reappearances of lesions during the swabbing period/total days assessed) across treatments
timeFrame: MAD Cohorts: At pre-specified time points from Days 8 to 36.
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: East Sydney Doctors
state: New South Wales
city: Miranda
country: Australia
facility: Sutherland Shire Clinical Research
state: New South Wales
city: Surry Hills
country: Australia
facility: Taylor Square Private Clinic
state: New South Wales
city: Sydney
country: Australia
facility: Momentum Clinical Research
state: New South Wales
city: Sydney
country: Australia
facility: Northern Beaches Clinical Research
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Clinical Research
state: New South Wales
city: Southport
country: Australia
facility: Gold Coast Sexual Health Centre
state: Queensland
city: Melbourne
country: Australia
facility: Momentum Sunshine
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research Christchurch
city: Hamilton
country: New Zealand
facility: Pacific Clinical Research Network - Hamilton
city: Nelson
country: New Zealand
facility: Pacific Clinical Research Network - Tasman
city: Palmerston North
country: New Zealand
facility: Momentum Palmerston North
city: Rotorua
country: New Zealand
facility: Pacific Clinical Research Network - Rotorua
city: Upper Hutt
country: New Zealand
facility: Pacific Clinical Research Network - Wellington
city: Waikanae
country: New Zealand
facility: Momentum Kapiti
Study officials:
References: