Recurrent Genital Herpes Simplex Type 2
Conditions
Keywords
ABI-5366, PK, Healthy Participants, HSV-2, Recurrent Genital Herpes
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.
Interventions
DRUGABI-5366
Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD)
DRUGABI-5366 Placebo
Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD)
Sponsors
Assembly Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| 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
| 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. |
Countries
Australia, New Zealand
Outcome results
None listed