First-in-human data show XT1061 tolerable in healthy volunteers
A Phase Ia study of the hepatitis B capsid assembly modulator XT1061 found dose-proportional exposure and no difference in adverse events versus placebo, clearing the way for patient trials.
Executive Summary
- A first-in-human study measured the pharmacokinetics, safety, and tolerability of a novel oral core protein allosteric modulator intended for chronic hepatitis B, using single ascending doses and a multiple-dose regimen in healthy volunteers.
- The compound was tolerated across the dose range tested, with no difference in adverse events between active drug and placebo, and its exposure rose in step with dose.
- Food intake lowered peak plasma concentration without materially changing total drug exposure, a finding that will inform how the drug is dosed relative to meals in later studies.
- The safety and exposure profile established here forms the basis for testing the drug's efficacy and safety in patients living with chronic hepatitis B.
The study
XT1061 is an oral small-molecule drug designed to promote the assembly of empty viral capsids that lack pregenomic RNA, a mechanism intended to interrupt the hepatitis B virus replication cycle. This first-in-human trial tested the drug's pharmacokinetic profile, safety, and tolerability in healthy Chinese subjects rather than in patients with chronic hepatitis B, the population the drug is ultimately intended to treat. First-in-humanFirst-in-human study on the pharmacokinetics, safety, and tolerability of single escalating doses and multiple doses of XT1061, a novel core protein allosteric modulator, in healthy Chinese subjects.Jul 15, 2026
How it was done
The Phase Ia study had two parts: a double-blind, randomized, placebo-controlled single-ascending-dose assessment under fasting conditions across doses from 12.5 mg to 600 mg, including a food-effect evaluation at 62.5 mg, followed by a multiple-dose regimen at 250 mg under fasting conditions. The design let investigators characterize the drug's dose-exposure relationship, its accumulation with repeat dosing, and the effect of food on absorption, alongside routine safety monitoring. First-in-humanFirst-in-human study on the pharmacokinetics, safety, and tolerability of single escalating doses and multiple doses of XT1061, a novel core protein allosteric modulator, in healthy Chinese subjects.Jul 15, 2026
The safety and PK result
The trial reported no difference in adverse event incidence between the XT1061 and placebo groups. Median time to peak concentration ranged from 1.0 to 2.5 hours, and the mean elimination half-life ranged from 2.864 to 11.478 hours. Systemic exposure increased in an approximately dose-proportional manner across the tested range, and steady-state concentrations were reached within about 2 days of repeated dosing, with mean accumulation indices between 1.043 and 1.333. First-in-humanFirst-in-human study on the pharmacokinetics, safety, and tolerability of single escalating doses and multiple doses of XT1061, a novel core protein allosteric modulator, in healthy Chinese subjects.Jul 15, 2026
The food effect
Concomitant food intake reduced peak plasma concentration by approximately 50% but had no material effect on total systemic exposure as measured by area under the curve. That combination, a lower peak with preserved total exposure, is the kind of finding that shapes dosing instructions (with or without food) carried into later-phase trials rather than raising a tolerability concern. First-in-humanFirst-in-human study on the pharmacokinetics, safety, and tolerability of single escalating doses and multiple doses of XT1061, a novel core protein allosteric modulator, in healthy Chinese subjects.Jul 15, 2026
What it means for development
The authors concluded that the favorable safety profile and predictable pharmacokinetics provide a foundation for advancing XT1061 into further clinical investigation of its efficacy and safety in patients with chronic hepatitis B. Chronic hepatitis B lacks a functional cure, and core protein allosteric modulators are one mechanism class investigators have pursued to interrupt viral replication beyond existing nucleos(t)ide therapies; this dataset addresses only the drug's tolerability and exposure in healthy volunteers, not its antiviral activity. First-in-humanFirst-in-human study on the pharmacokinetics, safety, and tolerability of single escalating doses and multiple doses of XT1061, a novel core protein allosteric modulator, in healthy Chinese subjects.Jul 15, 2026
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.