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

Hepatitis B, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03125213
• Other study ID #: AL-3778-1003
• Status: Withdrawn
• Phase: Phase 2
• First received: April 12, 2017
• Last updated: October 13, 2017
• Start date: September 12, 2017
• Est. completion date: February 15, 2019

Study information

• Verified date: October 2017
• Source: Alios Biopharma Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 15, 2019
• Est. primary completion date: February 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• AL-3778
AL-3778 tablets
• Peginterferon Alfa-2A
Peginterferon Alfa-2A for subcutaneous injection
• Placebo Oral Tablet
Placebo to Match AL-3778 tablet

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Alios Biopharma Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change (measured in log10 IU/mL) in serum HBsAg from baseline at Week 24.		Day 1 to Week 24
Secondary	Incidence and severity of AEs		Screening to Week 72
Secondary	Incidence and severity of laboratory abnormalities		Screening to Week 72
Secondary	Incidence of serious adverse events (SAEs).		Screening to Week 72
Secondary	Incidence and severity of AEs leading to study drug discontinuation.		Screening to Week 72
Secondary	Changes in serum HBV DNA over time		Day 1 to Week 72
Secondary	Proportion of subjects with ALT normalization		Day 1 to Week 72
Secondary	Incidence and severity of hepatic flares on treatment		Day 1 to Week 48
Secondary	Incidence and severity of hepatic flares off-treatment.		Week 48 to week 72
Secondary	Proportions of subjects with HBeAg loss and/or seroconversion.		Day 1 to Week 72
Secondary	Proportions of subjects with HBsAg loss and/or seroconversion.		Day 1 to Week 72
Secondary	Changes in serum HBsAg and serum HBeAg levels over time.		Day 1 to Week 72
Secondary	Proportion of subjects experiencing a viral breakthrough on treatment.		Day 1 to Week 48
Secondary	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
Secondary	Individually derived Bayesian estimates of AL-3778 Steady state plasma concentration (C0h)		Week 2
Secondary	Individually derived Bayesian estimates of AL-3778 area under the plasma concentration curve vs time (AUC0-12h)		Week 2
Secondary	AL-3778 maximum observed plasma concentration (Cmax)		Week 2
Secondary	AL-3778 Steady state plasma concentration (C0h)		Week 2
Secondary	AL-3778 area under the plasma concentration curve vs time (AUC0-12h)		Week 2