Ignite Creation Date:
2025-12-25 @ 2:44 AM
Ignite Modification Date:
2025-12-26 @ 1:24 AM
Study NCT ID:
NCT06092333
Status:
RECRUITING
Last Update Posted:
2025-12-08
First Post:
2023-10-19
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
VIR-2218 and Peginterferon Alfa-2a for Chronic Hepatitis B
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Organization:
Study Overview
Official Title:
A Pilot Study of the Combination of VIR-2218 and Peginterferon Alfa-2a for Chronic Hepatitis B
Status:
RECRUITING
Status Verified Date:
2025-12-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
Chronic hepatitis B virus (HBV) infection affects 292 million people worldwide; 887,000 die each year from cirrhosis, liver cancer, and related issues. Treatment options are limited.
Objective:
To test 2 drugs (VIR-2218 and peginterferon) in people with mild or inactive HBV infection.
Eligibility:
People aged 18 to 65 years with mild or inactive HBV infection.
Design:
Participants will be screened. They will have blood tests and an eye exam. They will have imaging scans of the liver to check the health of the liver.
Participants will be in the study for over 2 years.
VIR-2218 is an injection given under the skin of the stomach, upper arm, or thigh. Participants will come to the clinic to receive this injection once a month for 6 months.
Peginterferon is also injected under the skin. Participants will have this shot once a week for 6 months. They may either inject themselves at home or come to the clinic to get the injections.
Participants will get just the VIR-2218 for 3 months, then both shots for 3 months, then just the peginterferon for 3 months.
Participants will have two 3-day stays in the hospital. Tests will include:
Liver biopsy. A sample of tissue will be taken from their liver. After the procedure, participants will lie on their right side for 2 hours and then on their back for 4 hours.
Fine needle aspiration. A small needle will be used to collect cells from the liver.
After the last injection of peginterferon, follow-up visits will continue in the outpatient clinic every 4 to 12 weeks.
Chronic hepatitis B virus (HBV) infection affects 292 million people worldwide; 887,000 die each year from cirrhosis, liver cancer, and related issues. Treatment options are limited.
Objective:
To test 2 drugs (VIR-2218 and peginterferon) in people with mild or inactive HBV infection.
Eligibility:
People aged 18 to 65 years with mild or inactive HBV infection.
Design:
Participants will be screened. They will have blood tests and an eye exam. They will have imaging scans of the liver to check the health of the liver.
Participants will be in the study for over 2 years.
VIR-2218 is an injection given under the skin of the stomach, upper arm, or thigh. Participants will come to the clinic to receive this injection once a month for 6 months.
Peginterferon is also injected under the skin. Participants will have this shot once a week for 6 months. They may either inject themselves at home or come to the clinic to get the injections.
Participants will get just the VIR-2218 for 3 months, then both shots for 3 months, then just the peginterferon for 3 months.
Participants will have two 3-day stays in the hospital. Tests will include:
Liver biopsy. A sample of tissue will be taken from their liver. After the procedure, participants will lie on their right side for 2 hours and then on their back for 4 hours.
Fine needle aspiration. A small needle will be used to collect cells from the liver.
After the last injection of peginterferon, follow-up visits will continue in the outpatient clinic every 4 to 12 weeks.
Detailed Description:
Study Description:
Up to 50 untreated, adult, male and female subjects with hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) with low level viremia and antigenemia (hepatitis B surface antigen (HBsAg)) without cirrhosis will be screened in order to enroll 10 subjects in an open-label, phase 2a, single site (NIH Clinical Center), single arm, proof-of-concept study of a siRNA (VIR-2218) administered as a lead-in followed by combination with peginterferon alfa-2a. The primary endpoint of the study is log decline in quantitative HBsAg (qHBsAg) level. Secondary objectives include safety, functional cure defined as undetectable HBsAg (\<low limit of detection (LLOD) 0.085 IU/ml) and sustained suppression of HBV DNA \[\<lower limit of quantification (LLOQ\]) \<10 IU/ml)\] 24 weeks after discontinuation of all treatment (study week 60), antiviral activity, and to understand immunological changes following reduction/removal of HBsAg and to evaluate novel markers to monitor treatment response. A tertiary objective will be to assess the durability of the primary endpoint at week 120 (84 weeks after stopping treatment). After screening, eligible subjects will undergo a baseline liver biopsy followed by subcutaneous (SC) administration of VIR-2218 every 4 weeks followed by a repeat liver biopsy at week 12. Thereafter, peginterferon alfa-2a 180 ug mcg SC weekly will be initiated in combination with VIR-2218 for 12 weeks followed by peginterferon alfa-2a alone weekly for another 12 weeks. Total treatment duration will be 36 weeks (6 doses of VIR-2218 and 24 doses of peginterferon alfa-2a). Fine needle aspirates of the liver and blood for peripheral blood mononuclear cells (PBMCs) will be collected throughout the study to assess intrahepatic and peripheral immune parameters, respectively.
Objectives:
Primary Objective
1\. To evaluate the effect of administration of VIR-2218 in combination with peginterferon alfa-2a on qHBsAg levels
Secondary Objectives
1. To evaluate the safety and tolerability of VIR-2218 in combination with peginterferon alfa-2a in non-cirrhotic adults with chronic HBV infection
2. To evaluate functional cure following administration of VIR-2218 in combination with peginterferon alfa-2a
3. To evaluate the antiviral activity of VIR-2218 in combination with peginterferon alfa-2a in non-cirrhotic adults with chronic hepatitis B virus (HBV) infection.
4. To evaluate the effects of VIR-2218 in combination with peginterferon alfa-2a on peripheral and intrahepatic immune responses in non-cirrhotic adults with chronic HBV infection
5. To evaluate for the development of antiviral resistance during administration of VIR-2218 in combination with peginterferon alfa-2a
Exploratory Objectives
1. To evaluate other markers of HBV infection
2. To evaluate potential biomarkers for host responses to infection and/or to therapy
3. To compare intrahepatic and peripheral immune response obtained by fine needle aspiration (FNA) and PBMC, respectively
4. To assess the durability of the primary endpoint at week 120 (84 weeks after all treatment is discontinued)
Endpoints:
Primary Endpoint
1\. Decline in log IU/mL quantitative HBsAg level 24 weeks after discontinuation of all treatment (study week 60)
Secondary Endpoints
1. Safety
2. Functional cure which is defined as undetectable HBsAg (\<0.085 IU/ml) AND sustained suppression of HBV DNA \[\< LLOQ\], \<10 IU/ml)\] for more than 6 months after discontinuation of all treatment
3. HBV DNA \<10 IU/ml at end of treatment and 6 months off treatment. The response will be reported as HBV DNA \<LLOQ target detected (TD) or target not detected (TND)
4. Changes in innate and adaptive host immune responses to HBV during and after treatment.
* Greater natural killer (NK) cell response to the first peginterferon injection (measured as increase in TNFrelated apoptosis-inducing ligand (TRAIL)-expressing natural killer (NK) cell within the first 6 hours after peginterferon injection) in patients in this study compared to historic control
* Preferential improvement of HBsAg-specific T cell responses (measured as increase in the frequency of interferon gamma (IFN-g) producing T cells from baseline to week 12, from baseline to week 36 and from baseline to week 84) as compared to HBV core and polymerasespecific T cell responses in the same patients.
Tertiary Endpoints
1. HBV RNA, hepatitis B core-related antigen (HBcrAg), HBV DNA by digital droplet polymerase chain reaction (ddPCR)
2. qHBsAg using an ultrasensitive assay with a LLOQ of 0.005 IU/mL
3. Analysis of stool samples for microbiota (16s rRNA gene sequencing), Fibroscan.
4. Exploratory analysis of additional immunological parameters in serum, blood and liver and/or use of additional analysis techniques to further our understanding of changes in immune function during/after treatment.
5. To assess the durability of the primary endpoint at week 120 (84 weeks after all treatment is discontinued)
Up to 50 untreated, adult, male and female subjects with hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) with low level viremia and antigenemia (hepatitis B surface antigen (HBsAg)) without cirrhosis will be screened in order to enroll 10 subjects in an open-label, phase 2a, single site (NIH Clinical Center), single arm, proof-of-concept study of a siRNA (VIR-2218) administered as a lead-in followed by combination with peginterferon alfa-2a. The primary endpoint of the study is log decline in quantitative HBsAg (qHBsAg) level. Secondary objectives include safety, functional cure defined as undetectable HBsAg (\<low limit of detection (LLOD) 0.085 IU/ml) and sustained suppression of HBV DNA \[\<lower limit of quantification (LLOQ\]) \<10 IU/ml)\] 24 weeks after discontinuation of all treatment (study week 60), antiviral activity, and to understand immunological changes following reduction/removal of HBsAg and to evaluate novel markers to monitor treatment response. A tertiary objective will be to assess the durability of the primary endpoint at week 120 (84 weeks after stopping treatment). After screening, eligible subjects will undergo a baseline liver biopsy followed by subcutaneous (SC) administration of VIR-2218 every 4 weeks followed by a repeat liver biopsy at week 12. Thereafter, peginterferon alfa-2a 180 ug mcg SC weekly will be initiated in combination with VIR-2218 for 12 weeks followed by peginterferon alfa-2a alone weekly for another 12 weeks. Total treatment duration will be 36 weeks (6 doses of VIR-2218 and 24 doses of peginterferon alfa-2a). Fine needle aspirates of the liver and blood for peripheral blood mononuclear cells (PBMCs) will be collected throughout the study to assess intrahepatic and peripheral immune parameters, respectively.
Objectives:
Primary Objective
1\. To evaluate the effect of administration of VIR-2218 in combination with peginterferon alfa-2a on qHBsAg levels
Secondary Objectives
1. To evaluate the safety and tolerability of VIR-2218 in combination with peginterferon alfa-2a in non-cirrhotic adults with chronic HBV infection
2. To evaluate functional cure following administration of VIR-2218 in combination with peginterferon alfa-2a
3. To evaluate the antiviral activity of VIR-2218 in combination with peginterferon alfa-2a in non-cirrhotic adults with chronic hepatitis B virus (HBV) infection.
4. To evaluate the effects of VIR-2218 in combination with peginterferon alfa-2a on peripheral and intrahepatic immune responses in non-cirrhotic adults with chronic HBV infection
5. To evaluate for the development of antiviral resistance during administration of VIR-2218 in combination with peginterferon alfa-2a
Exploratory Objectives
1. To evaluate other markers of HBV infection
2. To evaluate potential biomarkers for host responses to infection and/or to therapy
3. To compare intrahepatic and peripheral immune response obtained by fine needle aspiration (FNA) and PBMC, respectively
4. To assess the durability of the primary endpoint at week 120 (84 weeks after all treatment is discontinued)
Endpoints:
Primary Endpoint
1\. Decline in log IU/mL quantitative HBsAg level 24 weeks after discontinuation of all treatment (study week 60)
Secondary Endpoints
1. Safety
2. Functional cure which is defined as undetectable HBsAg (\<0.085 IU/ml) AND sustained suppression of HBV DNA \[\< LLOQ\], \<10 IU/ml)\] for more than 6 months after discontinuation of all treatment
3. HBV DNA \<10 IU/ml at end of treatment and 6 months off treatment. The response will be reported as HBV DNA \<LLOQ target detected (TD) or target not detected (TND)
4. Changes in innate and adaptive host immune responses to HBV during and after treatment.
* Greater natural killer (NK) cell response to the first peginterferon injection (measured as increase in TNFrelated apoptosis-inducing ligand (TRAIL)-expressing natural killer (NK) cell within the first 6 hours after peginterferon injection) in patients in this study compared to historic control
* Preferential improvement of HBsAg-specific T cell responses (measured as increase in the frequency of interferon gamma (IFN-g) producing T cells from baseline to week 12, from baseline to week 36 and from baseline to week 84) as compared to HBV core and polymerasespecific T cell responses in the same patients.
Tertiary Endpoints
1. HBV RNA, hepatitis B core-related antigen (HBcrAg), HBV DNA by digital droplet polymerase chain reaction (ddPCR)
2. qHBsAg using an ultrasensitive assay with a LLOQ of 0.005 IU/mL
3. Analysis of stool samples for microbiota (16s rRNA gene sequencing), Fibroscan.
4. Exploratory analysis of additional immunological parameters in serum, blood and liver and/or use of additional analysis techniques to further our understanding of changes in immune function during/after treatment.
5. To assess the durability of the primary endpoint at week 120 (84 weeks after all treatment is discontinued)
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 001606-DK | None | None | View |