A Phase 2a, Randomized, Double-blind, Placebo-controlled Study Evaluating the Safety, Efficacy, and Pharmacokinetics of AL-3778 in Combination With Peginterferon Alpha-2a in Treatment Naïve Chronic Hepatitis B Subjects Who Are HBeAg-positive

Alios Biopharma Inc.0 sitesSeptember 12, 2017

ConditionsHepatitis B, Chronic

InterventionsAL-3778 Peginterferon Alfa-2A Placebo Oral Tablet

DrugsAL-3778 Peginterferon Alfa-2A Placebo Oral Tablet

Overview

Phase: Phase 2
Intervention: AL-3778
Conditions: Hepatitis B, Chronic
Sponsor: Alios Biopharma Inc.
Primary Endpoint: Mean change (measured in log10 IU/mL) in serum HBsAg from baseline at Week 24.
Status: Withdrawn
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This is a Phase 2a, multi-center, randomized, double-blind, placebo-controlled study evaluating the safety, efficacy, and pharmacokinetics (PK) of AL-3778 in combination with Peg-IFN in subjects with Hepatitis B e antigen (HBeAg) positive CHB virus infection who are treatment-naïve.

The study will consist of a screening phase , a double-blind treatment phase followed by treatment with Peg-IFN alone, and a post-treatment follow-up phase.

Approximately 30 subjects to complete the study. Eligible subjects will be randomized into 2 treatment arms in a 2:1 ratio (active:placebo) to receive one of the following treatments:

Arm A: Peg-IFN plus AL-3778 (N=20)
Arm B: Peg-IFN plus matching placebo (N=10)

Registry

clinicaltrials.gov

Start Date

September 12, 2017

End Date

February 15, 2019

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Alios Biopharma Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•A female subject must be of non-childbearing potential
•Subjects must have CHB infection, documented by serologic profile consistent for CHB infection at screening:
•serum HBsAg positive (for \>6 months)
•serum IgM anti-HBc negative
•Subjects are treatment-naïve and are serum HBeAg positive with:
•serum HBV DNA \>=20,000 IU /mL at screening
•HBsAg \>250 IU/mL at screening
•≥2× upper limit of normal (ULN) ALT and ≤5× ULN at screening

Exclusion Criteria

•Positive test for hepatitis A virus immunoglobulin, hepatitis delta antibody (Ab), hepatitis C Ab, human immunodeficiency virus (HIV) Ab and/or evidence of clinically relevant active infection that would interfere with study conduct or its interpretation would also lead to exclusion.
•Positive test for anti-HBs antibodies and anti-HBe antibodies.
•Subjects must have low levels of liver fibrosis that is classified as Metavir F0-F2
•Any history or current evidence of hepatic decompensation
•Subjects must have absence of hepatocellular carcinoma
•Subject with evidence of retinopathy on retinal fundus photographs
•Exclusions related to interferon use for the purposes of this study
•Subjects with one or more of the following laboratory abnormalities at screening
•serum creatinine elevation \>1.0× ULN
•hemoglobin \<11 g/dL \[males\], \<10.5 g/dL \[females\]

Arms & Interventions

Peg-IFN plus AL-3778

Intervention: AL-3778

Peg-IFN plus AL-3778

Intervention: Peginterferon Alfa-2A

Peg-IFN plus matching placebo

Intervention: Peginterferon Alfa-2A

Peg-IFN plus matching placebo

Intervention: Placebo Oral Tablet

Outcomes

Primary Outcomes

Mean change (measured in log10 IU/mL) in serum HBsAg from baseline at Week 24.

Time Frame: Day 1 to Week 24

Secondary Outcomes

Individually derived Bayesian estimates of AL-3778 Steady state plasma concentration (C0h)(Week 2)
Individually derived Bayesian estimates of AL-3778 area under the plasma concentration curve vs time (AUC0-12h)(Week 2)
Proportion of subjects with ALT normalization(Day 1 to Week 72)
Incidence and severity of hepatic flares on treatment(Day 1 to Week 48)
Incidence and severity of hepatic flares off-treatment.(Week 48 to week 72)
Proportions of subjects with HBeAg loss and/or seroconversion.(Day 1 to Week 72)
Proportions of subjects with HBsAg loss and/or seroconversion.(Day 1 to Week 72)
Changes in serum HBsAg and serum HBeAg levels over time.(Day 1 to Week 72)
Proportion of subjects experiencing a viral breakthrough on treatment.(Day 1 to Week 48)
Assess emergence of treatment-associated mutations during study treatment and follow-up with a focus on subjects with treatment failure(Day 1 to Week 72)
Incidence and severity of AEs(Screening to Week 72)
Incidence and severity of laboratory abnormalities(Screening to Week 72)
Incidence of serious adverse events (SAEs).(Screening to Week 72)
Incidence and severity of AEs leading to study drug discontinuation.(Screening to Week 72)
Changes in serum HBV DNA over time(Day 1 to Week 72)
AL-3778 maximum observed plasma concentration (Cmax)(Week 2)
AL-3778 Steady state plasma concentration (C0h)(Week 2)
AL-3778 area under the plasma concentration curve vs time (AUC0-12h)(Week 2)