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

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

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)

Study Overview

• Status: Withdrawn
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: AL-3778; Drug: Peginterferon Alfa-2A; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Peg-IFN plus AL-3778	Drug: AL-3778; AL-3778 tablets; Drug: Peginterferon Alfa-2A; Peginterferon Alfa-2A for subcutaneous injection
Placebo Comparator: Peg-IFN plus matching placebo	Drug: Peginterferon Alfa-2A; Peginterferon Alfa-2A for subcutaneous injection; Drug: Placebo Oral Tablet; Placebo to Match AL-3778 tablet

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Alios Biopharma Inc.
• Investigators: Study Director: William Kennedy, Alios Biopharma Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 12, 2017
• Primary Completion (Anticipated): February 15, 2019
• Study Completion (Anticipated): February 15, 2019

Study Registration Dates

• First Submitted: April 12, 2017
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Actual): October 16, 2017
• Last Update Submitted That Met QC Criteria: October 13, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2a
• Other Study ID Numbers: AL-3778-1003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No