Phase 1b clinical trialPhase 1b clinical trial
Evaluating the ability of ATI-2173 to reduce clevudine exposure and viral reductions
The safety, tolerability, pharmacokinetics (PK), and antiviral activity of ATI-2173 was tested in ANTT101, a phase 1, double-blind study in healthy subjects and subjects with chronic hepatitis B virus (HBV).1
Study design
ATI-2173 was administered in an oral capsule as 10-, 25-, and 50-mg multiple ascending dose (MAD) 28-day cohorts.1
Twenty-five subjects were randomized to the 28-day HBV-infected MAD cohort and 24 completed the dosing period. One subject in the 25-mg arm discontinued on day 4 for personal reasons and is not included in the data tables as they did not complete the dosing period.1
The PK population included all subjects who received at least 1 dose of the investigational product and have sufficient PK data to derive at least 1 PK parameter.1
Study results
ATI-2173 significantly reduces systemic clevudine exposure
- In a phase 1b study, ATI-2173 was rapidly cleared from the blood within 4 to 6 hours2
- Systemic clevudine exposure was dose related and only a fraction of a 30 mg clevudine dose2
- 56 ng/mL was the historical clevudine Cmin during treatment3
- Following daily treatment with ATI-2173 at 10, 25, and 50 mg doses for 28 days, clevudine AUC24 plasma exposure was lower than historically seen with a 30 mg dose of clevudine: 5%, 13%, and 34%, respectively
aPercent historical value was calculated by dividing the mean plasma clevudine PK parameter following 28 days of ATI-2173 administration by the mean plasma clevudine PK parameter reported following administration of clevudine 30 mg for 12 weeks.3
All doses of ATI-2173 demonstrated potent antiviral activity4
Viral reductions with ATI-2173 corresponded to those seen previously with clevudine treatment: 2.5 to 3 log10
- 25 mg ATI-2173 (n=5): 2.7 log10
- 50 mg ATI-2173 (n=6): 2.7 log10
- Placebo (n=7): 0.2 log10 increase
One month of ATI-2173 as monotherapy showed:
- Decreased markers of cccDNA activity in the blood
- Normalized alanine aminotransferase
- Prolonged off-treatment undetectable HBV DNA leading to an SVR24
- 9 out of 11 patients were BLQ within 1 month of dosing
AUC24, area under concentration-time curve from 0 to 24 hours; BLQ, below the limit of quantification; SVR24, sustained virologic response at 24 weeks.
References: 1. Data on file. Antios Therapeutics, Doylestown, PA. 2. Squires K, Ogilvie L, Huguet J, et al. Pharmacokinetics of ATI-2173, a novel active site polymerase inhibitor nucleotide (ASPIN), in a phase 1b clinical trial. Presented at: European Association for the Study of the Liver International Liver Congress; June 23-June 26, 2021. 3. Lim SG, Leung N, Hann HWL, et al. Clinical trial: a phase II, randomized study evaluating the safety, pharmacokinetics and anti-viral activity of clevudine for 12 weeks in patients with chronic hepatitis B. Aliment Pharmacol Ther. 2008;27(12):1282-1292. 4. Mayers DL, Jucov A, Anastasiy I, et al. Phase 1 results for ATI-2173, a novel active site polymerase inhibitor nucleotide (ASPIN), in HBV-infected subjects. Poster presented at: European Association for the Study of the Liver International Liver Congress; June 23-June 26, 2021.