INACTIVE: Peg-interferon for Inactive Chronic Hepatitis B Carriers

Sponsor

Seng Gee Lim (Other)

Overall Status

Unknown status

CT.gov ID

NCT02992704

Collaborator

Roche Pharma AG (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Chronic Hepatitis B carriers (normal LFTs and viral load < 2 x 10^4 IU/ml are not recommended to be treated by guidelines as they are at low risk for complications. However, it is unclear if treatment can enhance HBsAg loss which has been shown to be associated with significantly lower risk of complications compared to those without HBsAg loss. Consequently, this is a proof of concept study to determine the possibility of HBsAg loss in Chronic Hepatitis B carriers in a randomised open label clinical trial comparing no treatment to 24 weeks peg-interferon alpha 2a or 48 weeks peginterferon alpha 2a (randomised 1:1:1). The primary endpoint of HBsAg loss will be evaluated 24 weeks after the end of therapy for those on therapy and matched to an equivalent timepoint in the control arm. The sample size calculation is 30 patients in each arm for a 20% difference between any experimental arm and the control arm.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis, B Virus Carrier of Viral Hepatitis Type B	Drug: Peginterferon Alfa-2A	Phase 2/Phase 3

Detailed Description

Hypothesis: Chronic hepatitis B carriers (defined as HBeAg negative hepatitis B patients with HBV DNA <2x104 IU/mL, absence of cirrhosis and normal ALT) may experience higher rates of HBsAg seroclearance with pegylated interferon therapy.

2A. Primary Objective

The proportion of subjects with HBsAg loss at Week 24 of followup after treatment with 24 or 48 weeks of pegylated interferon alpha 2a compared to no therapy.

2B. Secondary Objective

The proportion of subjects who experience HBsAg loss with 24 versus 48 weeks of pegylated interferon at the end of treatment, and at end of followup.
The rate of quantitative HBsAg decline in relation to HBsAg loss
The proportion of subjects with virological response (HBV DNA level <13.5IU/mL) at Weeks 12 and 24 of treatment, and week 24 of followup.

2C Study population: 90 patient will be enrolled.

3.1 Inclusion Criteria

For entry into this study, the following inclusion criteria must be met:

Males or females age 21-75 years old (inclusive)
Treatment naïve
Documented HBsAg or HBV DNA positive for ≥ 6 months.
Documented HBeAg negative and anti-HBe positive
ALT ≤1xULN
quantitative HBsAg <1,000 IU/ml OR HBV DNA <2x104 IU/mL at screening
Absence of cirrhosis documented by liver biopsy or transient elastography within 6 months (Fibroscan®; Fibrosis stage >2 (score ≥ 10Kpa) will not be eligible for this study.)
Patient has agreed not to take any other investigational drug or systemic anti-viral, cytotoxic, corticosteroid, immunomodulatory agents or Chinese traditional remedies unless clinically indicated.
Patient is able to give written consent prior to study start and to comply with the study requirements.
Women of childbearing age must have a negative urine (ß-HCG) pregnancy test taken within 14 days of starting therapy

3.2 Exclusion Criteria

For entry into this study, the following exclusion criteria must not be met:

Patients who are currently on treatment with nucleoside/nucleotide analogues or have been treated for Hepatitis B in the past
Presence of cirrhosis documented by liver biopsy or transient elastography (score ≥ 10kpa)
Active Co-infection with HIV antibody, HCV antibody or HDV antibody positivity.
Evidence of decompensated liver disease defined as a direct (conjugated) bilirubin >1.2x upper limit of normal (ULN), prothrombin time (PT) >1.5xULN , serum bilirubin <35g/L, or prior history of clinical hepatic decompensation as illustrated by presence of (eg. ascites, encephalopathy, variceal haemorrhage)
Evidence of hepatocellular carcinoma
Absolute neutrophil count <1.5x10^{9/L or Hemoglobin <12 g/L for men or <11 g/L for
women, or platelet count < 90x10}9/L
History of depression or psychiatric disease
Uncontrolled thyroid disease defined as thyroid-stimulating hormone (TSH) >1.2 ULN or 0.8xLLN or thyroid dysfunction
Any immunomodulators, systemic cytotoxic agents, or systemic cortiosteriods within 6 months before trial entry
Significant renal, cardiovascular, pulmonary, neurological, autoimmune disease or bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses, multiple bone fractures)
Malignant disease within 5 years of trial entry
Women who are pregnant and who are not practicing adequate birth control measures, (defined as two methods of birth control with at least one barrier method) or who are lactating.

4.1 Study Treatment

Product, Dose, and Mode of Administration:

Peginterferon α-2a (PEG), 180mcg, will be administered weekly by subcutaneous injection for the specified period of time (see Study Design, Arms B and C). Pegasys® (Roche Pharmaceuticals).

Reference Therapy, Dose, and Mode of Administration:

Peginterferon α-2a (PEG), 180mcg subcutaneous injection once weekly

4.2 Overview The study will be conducted as a computer randomised clinical trial with concealment of allocation. Patients fulfilling inclusion and exclusion criteria will be randomised after completing screening. Patients will be randomly allocated to three parallel arms: no therapy, 24 weeks peg-interferon alpha 2a, and 48 weeks interferon alpha 2a. Patients will be monitored 4 weekly initial then 12 weekly till end of therapy, then for an additional 24 weeks after completing therapy. Patients on no therapy will be monitored for 72 weeks.

4.3 Endpoints/efficacy assessements Primary: HBsAg loss at end of followup for interferon arms compared to no therapy

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Three arm, parallel open label studyThree arm, parallel open label study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomised Control Study for Inactive Chronic Hepatitis B Patients With Low Viral Load, With Peg-Interferon (INACTIVE)

Actual Study Start Date :

Aug 1, 2016

Anticipated Primary Completion Date :

Aug 1, 2019

Anticipated Study Completion Date :

Aug 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PEG 24 weeks peginterferon alpha 2a 180mcg for 24 weeks	Drug: Peginterferon Alfa-2A peginterferon alpha 2a 180mcg weekly for either 24 or 48 weeks Other Names: pegasys
Experimental: PEG 48 weeks peginterferon alpha 2a 180mcg 48 weeks	Drug: Peginterferon Alfa-2A peginterferon alpha 2a 180mcg weekly for either 24 or 48 weeks Other Names: pegasys
No Intervention: Control No treatment for 72 weeks

Arm

Intervention/Treatment

Experimental: PEG 24 weeks

peginterferon alpha 2a 180mcg for 24 weeks

Drug: Peginterferon Alfa-2A

peginterferon alpha 2a 180mcg weekly for either 24 or 48 weeks

Other Names:

pegasys

Experimental: PEG 48 weeks

peginterferon alpha 2a 180mcg 48 weeks

Drug: Peginterferon Alfa-2A

peginterferon alpha 2a 180mcg weekly for either 24 or 48 weeks

Other Names:

pegasys

No Intervention: Control

No treatment for 72 weeks

Outcome Measures

Primary Outcome Measures

HBsAg loss [24 weeks after end of therapy]
Qualitative HBsAg assay reads "non-detectable"

Secondary Outcome Measures

HBsAg loss [At the end of 24 and 48 weeks of peginterferon therapy]
Qualitative HBsAg assay reads "non-detectable"
Decline in quantitative HBsAg level [At week 24, 48 and 24 weeks after completion of therapy]
Based on quantitative HBsAg assay
proportion of patients with undetectable HBV DNA [At week 24, 48 of therapy, and 24 weeks after end of therapy]
HBV DNA assay<13.5 IU/ml

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Treatment naïve
Documented HBsAg or HBV DNA positive for ≥ 6 months.
Documented HBeAg negative and anti-HBe positive
ALT ≤1xULN
quantitative HBsAg <1,000 IU/ml
HBV DNA <2x104 IU/mL at screening
Absence of cirrhosis documented by liver biopsy or transient elastography within 6 months (Fibroscan®; Fibrosis stage >2 (score ≥ 10Kpa) will not be eligible for this study.)
Patient has agreed not to take any other investigational drug or systemic anti-viral, cytotoxic, corticosteroid, immunomodulatory agents or Chinese traditional remedies unless clinically indicated.
Patient is able to give written consent prior to study start and to comply with the study requirements.
Women of childbearing age must have a negative urine (ß-HCG) pregnancy test taken within 14 days of starting therapy

Exclusion Criteria:

Patients who are currently on treatment with nucleoside/nucleotide analogues or have been treated for Hepatitis B in the past
Presence of cirrhosis documented by liver biopsy or transient elastography (score ≥ 10kpa)
Active Co-infection with HIV antibody, HCV antibody or HDV antibody positivity.
Evidence of decompensated liver disease defined as a direct (conjugated) bilirubin

1.2x upper limit of normal (ULN), prothrombin time (PT) >1.5xULN , serum bilirubin <35g/L, or prior history of clinical hepatic decompensation as illustrated by presence of (eg. ascites, encephalopathy, variceal haemorrhage)

Evidence of hepatocellular carcinoma
Absolute neutrophil count <1.5x10^{9/L or Hemoglobin <12 g/L for men or <11 g/L for
women, or platelet count < 90x10}9/L
History of depression or psychiatric disease
Uncontrolled thyroid disease defined as thyroid-stimulating hormone (TSH) >1.2 ULN or 0.8xLLN or thyroid dysfunction
Any immunomodulators, systemic cytotoxic agents, or systemic cortiosteriods within 6 months before trial entry
Significant renal, cardiovascular, pulmonary, neurological, autoimmune disease or bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses, multiple bone fractures)
Malignant disease within 5 years of trial entry
Women who are pregnant and who are not practicing adequate birth control measures, (defined as two methods of birth control with at least one barrier method) or who are lactating.