Clinical trial NCT03125213: A Study Evaluating AL-3778 in Combination With Peginterferon Alpha-2a in Chronic Hepatitis B Subjects
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Alios Biopharma Inc.
Sponsor class: INDUSTRY
First posted: 2017-04-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility 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).

Primary outcomes:
measure: Mean change (measured in log10 IU/mL) in serum HBsAg from baseline at Week 24.
timeFrame: Day 1 to Week 24
Secondary outcomes:
measure: Incidence and severity of AEs
timeFrame: Screening to Week 72
measure: Incidence and severity of laboratory abnormalities
timeFrame: Screening to Week 72
measure: Incidence of serious adverse events (SAEs).
timeFrame: Screening to Week 72
measure: Incidence and severity of AEs leading to study drug discontinuation.
timeFrame: Screening to Week 72
measure: Changes in serum HBV DNA over time
timeFrame: Day 1 to Week 72
measure: Proportion of subjects with ALT normalization
timeFrame: Day 1 to Week 72
measure: Incidence and severity of hepatic flares on treatment
timeFrame: Day 1 to Week 48
measure: Incidence and severity of hepatic flares off-treatment.
timeFrame: Week 48 to week 72
measure: Proportions of subjects with HBeAg loss and/or seroconversion.
timeFrame: Day 1 to Week 72
measure: Proportions of subjects with HBsAg loss and/or seroconversion.
timeFrame: Day 1 to Week 72
measure: Changes in serum HBsAg and serum HBeAg levels over time.
timeFrame: Day 1 to Week 72
measure: Proportion of subjects experiencing a viral breakthrough on treatment.
timeFrame: Day 1 to Week 48
measure: Assess emergence of treatment-associated mutations during study treatment and follow-up with a focus on subjects with treatment failure
timeFrame: Day 1 to Week 72
measure: Individually derived Bayesian estimates of AL-3778 Steady state plasma concentration (C0h)
timeFrame: Week 2
measure: Individually derived Bayesian estimates of AL-3778 area under the plasma concentration curve vs time (AUC0-12h)
timeFrame: Week 2
measure: AL-3778 maximum observed plasma concentration (Cmax)
timeFrame: Week 2
measure: AL-3778 Steady state plasma concentration (C0h)
timeFrame: Week 2
measure: AL-3778 area under the plasma concentration curve vs time (AUC0-12h)
timeFrame: Week 2
Other outcomes:
Locations:
Study officials:
affiliation: Alios Biopharma Inc.
name: William Kennedy
role: STUDY_DIRECTOR
References: