Study of Sequential GSK3228836 and Peginterferon Treatment in Participants With Chronic Hepatitis B (CHB)

NCT04676724 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 209348
• Study Type: interventional
• Target: 108
• Locations: 11 countries
• Sites: 49

Brief Summary

This study is intended to evaluate if 12 or 24 weeks of treatment with GSK3228836 followed by up to 24 weeks of pegylated interferon (PegIFN) can increase the rate of hepatitis B virus surface antigen (HBsAg) loss in participants on stable nucleos(t)ide analogue (NA) therapy, and whether virologic response can be sustained once PegIFN treatment is discontinued. Participants will be randomized to receive GSK3228836 for 12 or 24 weeks followed by up to 24 weeks of PegIFN.

Conditions

Hepatitis B

Keywords

Chronic Hepatitis B; GSK3228836; Pegylated interferon; Nucleos(t)ide analogue; Sustained virologic response

Outcome Measures

Primary Outcomes (2)

• Treatment Arm 1 - Percentage of Participants Achieving Sustained Virologic Response (SVR) for 24 Weeks After End of Treatment

  Sustained virologic response is defined as undetectable levels of Hepatitis B surface antigen (HBsAg) and Hepatitis-B virus deoxy-ribonucleic acid (HBV DNA) on treatment. The SVR was a composite endpoint defined as HBsAg and HBV DNA levels were less than (\<) Lower limit of quantitation (LLOQ) at the planned end of sequential treatment of GSK3228836 and PegIFN treatment which is sustained for 24 weeks post-GSK3228836 and PegIFN treatment in the absence of any rescue medication. Percentage values are rounded-off.

  Up to 24 weeks off treatment (Study Weeks 48 to 72)

• Treatment Arm 2 - Percentage of Participants Achieving Sustained Virologic Response (SVR) for 24 Weeks After End of Treatment

  Sustained virologic response is defined as undetectable levels of Hepatitis B surface antigen (HBsAg) and Hepatitis-B virus deoxy-ribonucleic acid (HBV DNA) on treatment. The SVR was a composite endpoint defined as HBsAg and HBV DNA levels were less than (\<) Lower limit of quantitation (LLOQ) at the planned end of sequential treatment of GSK3228836 and PegIFN treatment which is sustained for 24 weeks post-GSK3228836 and PegIFN treatment in the absence of any rescue medication. Percentage values are rounded-off.

  Up to 24 weeks off treatment (Study Weeks 36 to 60)

Secondary Outcomes (33)

• Treatment Arm 1: Percentage of Participants Achieving HBsAg and HBV DNA < Lower Limit of Quantitation (LLOQ)

  End of treatment (up to 48 weeks) and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

• Treatment Arm 2: Percentage of Participants Achieving HBsAg and HBV DNA < Lower Limit of Quantitation (LLOQ)

  End of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60) and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

• Treatment Arm 1: Percentage of Participants With Categorical Changes From Baseline in HBsAg Values

  Baseline, End of treatment (up to 48 weeks), and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

• Treatment Arm 2: Percentage of Participants With Categorical Changes From Baseline in HBsAg Values

  Baseline, End of treatment (up to 36 weeks), up to 24 weeks off treatment follow-up (Study Weeks 36 to 60) and up to 36 weeks off treatment follow-up (Study Weeks 36 to 72)

• Treatment Arm 1: Number of Participants With Alanine Aminotransferase (ALT) Normalization

  At baseline, end of treatment (up to 48 weeks) and up to 24 weeks off treatment follow-up (Study Weeks 48 to 72)

Study Arms (2)

GSK3228836 300 mg (24 weeks) + PegIFN 180 mcg (24 weeks)

EXPERIMENTAL

Participants on stable NA therapy received 300 milligrams per week (mg/week) GSK3228836 for 24 weeks (plus a loading dose on Day 4 and 11), followed by Pegylated Interferon (PegIFN) 180 microgram per week (mcg/week) up to 24 weeks.

Drug: GSK3228836; Drug: PegIFN; Drug: NA therapy

GSK3228836 300 mg (12 weeks) + PegIFN 180 mcg (24 weeks)

EXPERIMENTAL

Participants on stable NA therapy received 300mg/week GSK3228836 for 12 weeks (plus a loading dose on Day 4 and 11), followed by PegIFN 180 mcg/week up to 24 weeks.

Drug: GSK3228836; Drug: PegIFN; Drug: NA therapy

Interventions

GSK3228836 DRUG

Participants will be administered GSK3228836.

GSK3228836 300 mg (12 weeks) + PegIFN 180 mcg (24 weeks); GSK3228836 300 mg (24 weeks) + PegIFN 180 mcg (24 weeks)

PegIFN DRUG

Participants will be administered PegIFN.

GSK3228836 300 mg (12 weeks) + PegIFN 180 mcg (24 weeks); GSK3228836 300 mg (24 weeks) + PegIFN 180 mcg (24 weeks)

NA therapy DRUG

Participants will continue to receive their NA therapy for the duration of the study.

GSK3228836 300 mg (12 weeks) + PegIFN 180 mcg (24 weeks); GSK3228836 300 mg (24 weeks) + PegIFN 180 mcg (24 weeks)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 75 years of age at the time of signing the informed consent.
• Participants who are eligible to be treated with PegIFN.
• Documented chronic HBV infection \>=6 months prior to screening and currently receiving stable NA therapy except telbivudine, defined as no changes to their NA regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study.
• Plasma or serum HBsAg concentration \>100 International Units per milliliter (IU/mL).
• Plasma or serum HBV DNA concentration \<90 IU/mL.
• ALT \<=2 times ULN.
• A male participant is eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of study treatment: a) Refrain from donating sperm; b) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or agree to use contraception/barrier: Agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak) when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
• A female participant is eligible to participate: a) If she is not pregnant or breastfeeding; b) at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1 percent per year), preferably with low user dependency during the intervention period and for at least 90 days after the last dose of study treatment.
• A WOCBP must have both a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Capable of giving signed informed consent.

You may not qualify if:

• Clinically significant abnormalities, aside from chronic HBV infection in medical history or physical examination.
• Co-infection with: Current or past history of Hepatitis C virus (HCV); Human immunodeficiency virus (HIV); Hepatitis D virus (HDV).
• Diagnosed or suspected hepatocellular carcinoma as evidenced by the following: Alpha- fetoprotein concentration \>=200 nanogram per milliliter (ng/mL); If the screening alpha fetoprotein concentration is \>=50 ng/mL and \<200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomization.
• History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer). Participants under evaluation for possible malignancy are not eligible.
• History of vasculitis or presence of symptoms and signs of potential vasculitis (e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause) or history/presence of other diseases that may be associated with vasculitis condition (e.g., systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex).
• History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension).
• Poorly controlled thyroid dysfunction or abnormal thyroid stimulating hormone (TSH) levels
• Low complement 3 (C3) at screening and evidence of past history or current manifestations of vasculitic/inflammatory/auto-immune conditions. All participants with low C3 at screening should have their medical history discussed with the Medical Monitor prior to enrolment.
• Pre-existing severe psychiatric condition or a history of severe psychiatric disorders, including severe depression, suicidal ideation and attempted suicide.
• Currently taking, or took within 3 months of screening, any immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (\<=2 weeks) or topical/inhaled steroid use.
• Participants for whom immunosuppressive treatment is not advised, including therapeutic doses of steroids, will be excluded.
• Participants with prior treatment with PegINF or interferon will be excluded
• Participants requiring anti-coagulation therapies (for example warfarin, Factor Xa inhibitors or anti-platelet agents like clopidogrel).
• Participants currently taking, or took within 6 months of screening, telbivudine.
• The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives (if known) or twice the duration (if known) of the biological effect of the study treatment (whichever is longer) or 90 days (if half-life or duration is unknown).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (49)

GSK Investigational Site

Sacramento, California, 95817, United States

Location

GSK Investigational Site

Iowa City, Iowa, 52242, United States

Location

GSK Investigational Site

Detroit, Michigan, 48202, United States

Location

GSK Investigational Site

New York, New York, 10016, United States

Location

GSK Investigational Site

Calgary, Alberta, T2N 4Z6, Canada

Location

GSK Investigational Site

Edmonton, Alberta, T6G 2X8, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 4E9, Canada

Location

GSK Investigational Site

Changchun, Jilin, 130021, China

Location

GSK Investigational Site

Beijing, 100015, China

Location

GSK Investigational Site

Beijing, 100069, China

Location

GSK Investigational Site

Hangzhou, 310000, China

Location

GSK Investigational Site

Shanghai, 200025, China

Location

GSK Investigational Site

Baggiovara (MO), Emilia-Romagna, 40126, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20122, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20157, Italy

Location

GSK Investigational Site

Monza (MB), Lombardy, 20900, Italy

Location

GSK Investigational Site

Aichi, 467-8602, Japan

Location

GSK Investigational Site

Fukui, 918-8503, Japan

Location

GSK Investigational Site

Gifu, 500-8717, Japan

Location

GSK Investigational Site

Hiroshima, 737-0023, Japan

Location

GSK Investigational Site

Kumamoto, 860-8556, Japan

Location

GSK Investigational Site

Nagasaki, 856-8562, Japan

Location

GSK Investigational Site

Tokyo, 113-8603, Japan

Location

GSK Investigational Site

Lublin, 20-884, Poland

Location

GSK Investigational Site

Mysłowice, 41-400, Poland

Location

GSK Investigational Site

Łańcut, 37-100, Poland

Location

GSK Investigational Site

Barnaul, 656010, Russia

Location

GSK Investigational Site

Chelyabinsk, 454052, Russia

Location

GSK Investigational Site

Moscow, 121170, Russia

Location

GSK Investigational Site

Novosibirsk, 630099, Russia

Location

GSK Investigational Site

Saint Petersburg, 190103, Russia

Location

GSK Investigational Site

Samara, 443063, Russia

Location

GSK Investigational Site

Красноярск, 660049, Russia

Location

GSK Investigational Site

Ennerdale, Gauteng, 1830, South Africa

Location

GSK Investigational Site

Johannesburg, Gauteng, 1401, South Africa

Location

GSK Investigational Site

Busan, 49241, South Korea

Location

GSK Investigational Site

Daegu, 41944, South Korea

Location

GSK Investigational Site

Gyeonggi-do, 15355, South Korea

Location

GSK Investigational Site

Gyeonggi-do, 463-712, South Korea

Location

GSK Investigational Site

Ulsan, 44033, South Korea

Location

GSK Investigational Site

Barcelona, 08011, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28031, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Santander, 39008, Spain

Location

GSK Investigational Site

London, WC1E 6JB, United Kingdom

Location

GSK Investigational Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

GSK Investigational Site

Nottingham, NG7 2UH, United Kingdom

Location

GSK Investigational Site

Plymouth, PL68DH, United Kingdom

Location

Related Publications (2)

• Joshi S, Freudenberg JM, Singh JM, Jordan WT, Felton L, Dixon S, Paff M, Theodore D, Walker J. Immunomodulation by bepirovirsen may induce killing of infected hepatocytes (B-Together study). Hepatol Int. 2025 Oct 3. doi: 10.1007/s12072-025-10917-0. Online ahead of print.

  PMID: 41042426 DERIVED

• Buti M, Heo J, Tanaka Y, Andreone P, Atsukawa M, Cabezas J, Chak E, Coffin CS, Fujiwara K, Gankina N, Gordon SC, Janczewska E, Komori A, Lampertico P, McPherson S, Morozov V, Plesniak R, Poulin S, Ryan P, Sagalova O, Sheng G, Voloshina N, Xie Q, Yim HJ, Dixon S, Paff M, Felton L, Lee M, Greene T, Lim J, Lakshminarayanan D, McGonagle G, Plein H, Youssef AS, Elston R, Kendrick S, Theodore D. Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B. J Hepatol. 2025 Feb;82(2):222-234. doi: 10.1016/j.jhep.2024.08.010. Epub 2024 Aug 29.

  PMID: 39214467 DERIVED

MeSH Terms

Conditions

Hepatitis B; Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomised in a ratio of 1:1 to one of two treatment arms: 24 weeks GSK3228836 followed by up to 24 weeks PegIFN, or 12 weeks GSK3228836 followed by up to 24 weeks PegIFN.

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 21, 2020
• Study Start: January 28, 2021
• Primary Completion: February 17, 2023
• Study Completion: February 17, 2023
• Last Updated: May 2, 2024
• Results First Posted: May 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

IT (4); ES (5); US (4); CN (5); JP (7); GB (4); PL (3); ZA (2); CA (3); RU (7); KR (5)