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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT03125213
• Date of registration: 12/04/2017
• Prospective Registration: Yes
• Primary sponsor: Alios Biopharma Inc.
• Public title: A Study Evaluating AL-3778 in Combination With Peginterferon Alpha-2a in Chronic Hepatitis B Subjects
• Scientific 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
• Date of first enrolment: September 12, 2017
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03125213
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Mauritius

Contacts

• Name: William Kennedy
• Affiliation: Alios Biopharma Inc.

Key inclusion & exclusion criteria

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).



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hepatitis B, Chronic

Intervention(s)

Drug: Peginterferon Alfa-2A

Drug: Placebo Oral Tablet

Drug: AL-3778

Primary Outcome(s)

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

Secondary Outcome(s)

AL-3778 maximum observed plasma concentration (Cmax) [Time Frame: Week 2]

Proportions of subjects with HBeAg loss and/or seroconversion. [Time Frame: Day 1 to Week 72]

Incidence and severity of AEs [Time Frame: Screening to Week 72]

Proportion of subjects with ALT normalization [Time Frame: Day 1 to Week 72]

Changes in serum HBsAg and serum HBeAg levels over time. [Time Frame: Day 1 to Week 72]

Changes in serum HBV DNA over time [Time Frame: Day 1 to Week 72]

Incidence and severity of AEs leading to study drug discontinuation. [Time Frame: Screening to Week 72]

Individually derived Bayesian estimates of AL-3778 area under the plasma concentration curve vs time (AUC0-12h) [Time Frame: Week 2]

Assess emergence of treatment-associated mutations during study treatment and follow-up with a focus on subjects with treatment failure [Time Frame: Day 1 to Week 72]

Individually derived Bayesian estimates of AL-3778 Steady state plasma concentration (C0h) [Time Frame: Week 2]

Proportion of subjects experiencing a viral breakthrough on treatment. [Time Frame: Day 1 to Week 48]

Incidence and severity of hepatic flares off-treatment. [Time Frame: Week 48 to week 72]

Incidence and severity of laboratory abnormalities [Time Frame: Screening to Week 72]

Proportions of subjects with HBsAg loss and/or seroconversion. [Time Frame: Day 1 to Week 72]

Incidence and severity of hepatic flares on treatment [Time Frame: Day 1 to Week 48]

Incidence of serious adverse events (SAEs). [Time Frame: Screening to Week 72]

AL-3778 area under the plasma concentration curve vs time (AUC0-12h) [Time Frame: Week 2]

AL-3778 Steady state plasma concentration (C0h) [Time Frame: Week 2]

Secondary ID(s)

AL-3778-1003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors