A Study Evaluating AL-3778 in Combination With Peginterferon Alpha-2a in Chronic Hepatitis B Subjects

Phase 2

Withdrawn

• Conditions: Hepatitis B, Chronic
• Interventions: Drug: Peginterferon Alfa-2A; Drug: AL-3778; Drug: Placebo Oral Tablet

• Registration Number: NCT03125213
• Lead Sponsor: Alios Biopharma Inc.

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-04-12
• Study First Submitted QC: 2017-04-19
• Study First Posted: 2017-04-24
• Study Start: 2017-09-12
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-13
• Last Update Posted: 2017-10-16
• Primary Completion: 2019-02-15
• Study Completion: 2019-02-15

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. A female subject must be of non-childbearing potential

2. Subjects must have CHB infection, documented by serologic profile consistent for CHB infection at screening:

   1. serum HBsAg positive (for >6 months)
   2. serum IgM anti-HBc negative

3. Subjects are treatment-naïve and are serum HBeAg positive with:

   1. serum HBV DNA >=20,000 IU /mL at screening
   2. HBsAg >250 IU/mL at screening
   3. ≥2× upper limit of normal (ULN) ALT and ≤5× ULN at screening

Exclusion Criteria

1. 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.

2. Positive test for anti-HBs antibodies and anti-HBe antibodies.

3. Subjects must have low levels of liver fibrosis that is classified as Metavir F0-F2

4. Any history or current evidence of hepatic decompensation

5. Subjects must have absence of hepatocellular carcinoma

6. Subject with evidence of retinopathy on retinal fundus photographs

7. Exclusions related to interferon use for the purposes of this study

8. Subjects with one or more of the following laboratory abnormalities at screening

   1. serum creatinine elevation >1.0× ULN
   2. hemoglobin <11 g/dL [males], <10.5 g/dL [females]
   3. platelet count <125× 109 cells/L
   4. absolute neutrophil count <1.0× 109 cells/L
   5. total bilirubin >1.0× ULN; unless known Gilbert's Disease or Dubin-Johnson Syndrome

9. Subjects having received an investigational agent or investigational vaccine, or having received a biological product within 12 weeks or 5 half-lives (whichever is longer) prior to baseline (first intake of study drugs).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Peg-IFN plus matching placebo	Peginterferon Alfa-2A	-
Peg-IFN plus matching placebo	Placebo Oral Tablet	-
Peg-IFN plus AL-3778	AL-3778	-
Peg-IFN plus AL-3778	Peginterferon Alfa-2A	-

Primary Outcome Measures

Name	Time	Method
Mean change (measured in log10 IU/mL) in serum HBsAg from baseline at Week 24.	Day 1 to Week 24

Secondary Outcome Measures

Name	Time	Method
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
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
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