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

Primary Purpose

Hepatitis B, Chronic

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

AL-3778

Peginterferon Alfa-2A

Placebo Oral Tablet

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

A female subject must be of non-childbearing potential
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
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:

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.
Positive test for anti-HBs antibodies and anti-HBe antibodies.
Subjects must have low levels of liver fibrosis that is classified as Metavir F0-F2
Any history or current evidence of hepatic decompensation
Subjects must have absence of hepatocellular carcinoma
Subject with evidence of retinopathy on retinal fundus photographs
Exclusions related to interferon use for the purposes of this study
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
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).

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Peg-IFN plus AL-3778

Peg-IFN plus matching placebo

Arm Description

Outcomes

Primary Outcome Measures

Mean change (measured in log10 IU/mL) in serum HBsAg from baseline at Week 24.

Secondary Outcome Measures

Incidence and severity of AEs

Incidence and severity of laboratory abnormalities

Incidence of serious adverse events (SAEs).

Incidence and severity of AEs leading to study drug discontinuation.

Changes in serum HBV DNA over time

Proportion of subjects with ALT normalization

Incidence and severity of hepatic flares on treatment

Incidence and severity of hepatic flares off-treatment.

Proportions of subjects with HBeAg loss and/or seroconversion.

Proportions of subjects with HBsAg loss and/or seroconversion.

Changes in serum HBsAg and serum HBeAg levels over time.

Proportion of subjects experiencing a viral breakthrough on treatment.

Assess emergence of treatment-associated mutations during study treatment and follow-up with a focus on subjects with treatment failure

Individually derived Bayesian estimates of AL-3778 Steady state plasma concentration (C0h)

Individually derived Bayesian estimates of AL-3778 area under the plasma concentration curve vs time (AUC0-12h)

AL-3778 maximum observed plasma concentration (Cmax)

AL-3778 Steady state plasma concentration (C0h)

AL-3778 area under the plasma concentration curve vs time (AUC0-12h)

Full Information

NCT ID

NCT03125213

First Posted

April 12, 2017

Last Updated

October 13, 2017

Sponsor

Alios Biopharma Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03125213

Brief Title

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

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Withdrawn

Why Stopped

Sponsor decision.

Study Start Date

September 12, 2017 (Anticipated)

Primary Completion Date

February 15, 2019 (Anticipated)

Study Completion Date

February 15, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alios Biopharma Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B, Chronic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Peg-IFN plus AL-3778

Arm Type

Active Comparator

Arm Title

Peg-IFN plus matching placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

AL-3778

Intervention Description

AL-3778 tablets

Intervention Type

Drug

Intervention Name(s)

Peginterferon Alfa-2A

Intervention Description

Peginterferon Alfa-2A for subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Tablet

Intervention Description

Placebo to Match AL-3778 tablet

Primary Outcome Measure Information:

Title

Mean change (measured in log10 IU/mL) in serum HBsAg from baseline at Week 24.

Time Frame

Day 1 to Week 24

Secondary Outcome Measure Information:

Title

Incidence and severity of AEs

Time Frame

Screening to Week 72

Title

Incidence and severity of laboratory abnormalities

Time Frame

Screening to Week 72

Title

Incidence of serious adverse events (SAEs).

Time Frame

Screening to Week 72

Title

Incidence and severity of AEs leading to study drug discontinuation.

Time Frame

Screening to Week 72

Title

Changes in serum HBV DNA over time

Time Frame

Day 1 to Week 72

Title

Proportion of subjects with ALT normalization

Time Frame

Day 1 to Week 72

Title

Incidence and severity of hepatic flares on treatment

Time Frame

Day 1 to Week 48

Title

Incidence and severity of hepatic flares off-treatment.

Time Frame

Week 48 to week 72

Title

Proportions of subjects with HBeAg loss and/or seroconversion.

Time Frame

Day 1 to Week 72

Title

Proportions of subjects with HBsAg loss and/or seroconversion.

Time Frame

Day 1 to Week 72

Title

Changes in serum HBsAg and serum HBeAg levels over time.

Time Frame

Day 1 to Week 72

Title

Proportion of subjects experiencing a viral breakthrough on treatment.

Time Frame

Day 1 to Week 48

Title

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

Title

Individually derived Bayesian estimates of AL-3778 Steady state plasma concentration (C0h)

Time Frame

Week 2

Title

Individually derived Bayesian estimates of AL-3778 area under the plasma concentration curve vs time (AUC0-12h)

Time Frame

Week 2

Title

AL-3778 maximum observed plasma concentration (Cmax)

Time Frame

Week 2

Title

AL-3778 Steady state plasma concentration (C0h)

Time Frame

Week 2

Title

AL-3778 area under the plasma concentration curve vs time (AUC0-12h)

Time Frame

Week 2

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: A female subject must be of non-childbearing potential Subjects must have CHB infection, documented by serologic profile consistent for CHB infection at screening: serum HBsAg positive (for >6 months) serum IgM anti-HBc negative Subjects are treatment-naïve and are serum HBeAg positive with: serum HBV DNA >=20,000 IU /mL at screening HBsAg >250 IU/mL at screening ≥2× upper limit of normal (ULN) ALT and ≤5× ULN at screening Exclusion Criteria: 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. Positive test for anti-HBs antibodies and anti-HBe antibodies. Subjects must have low levels of liver fibrosis that is classified as Metavir F0-F2 Any history or current evidence of hepatic decompensation Subjects must have absence of hepatocellular carcinoma Subject with evidence of retinopathy on retinal fundus photographs Exclusions related to interferon use for the purposes of this study Subjects with one or more of the following laboratory abnormalities at screening serum creatinine elevation >1.0× ULN hemoglobin <11 g/dL [males], <10.5 g/dL [females] platelet count <125× 109 cells/L absolute neutrophil count <1.0× 109 cells/L total bilirubin >1.0× ULN; unless known Gilbert's Disease or Dubin-Johnson Syndrome 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

William Kennedy

Organizational Affiliation

Alios Biopharma Inc.

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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