What is the mechanism of action of this treatment?

Common treatments for Hepatitis B, such as nucleos(t)ide analogs like entecavir and tenofovir, work by inhibiting the viral polymerase enzyme, which is crucial for viral DNA replication. This suppression of viral replication helps reduce the viral load in the patient's body, thereby limiting liver damage and reducing the risk of liver cancer. Investigational agents like GSK3228836 target HBV RNA, leading to reduced production of viral proteins, which may enhance the immune system's ability to control the virus. Understanding these mechanisms is vital for patients as it highlights the importance of these treatments in managing the disease and preventing severe complications.

What side effects are associated with this type of intervention?

Common treatments for Hepatitis B, such as nucleos(t)ide analogs (e.g., entecavir, tenofovir) and interferon-based therapies, have well-documented side effects. Nucleos(t)ide analogs are generally well-tolerated but can cause kidney dysfunction and bone mineral density loss. Interferon-based therapies often result in flu-like symptoms, fatigue, depression, and hematologic abnormalities. For investigational agents like GSK3228836, which targets HBV RNA, the safety profile is still being established, but early studies indicate an acceptable safety profile with dose-dependent reductions in HBsAg. Common side effects across these treatments include gastrointestinal disturbances, headache, and potential liver enzyme elevations.

What prior FDA approvals exist?

The FDA has approved several antiviral agents for the treatment of Hepatitis B, including nucleoside and nucleotide analogs such as tenofovir, entecavir, lamivudine, and adefovir dipivoxil. These drugs work by inhibiting the replication of the Hepatitis B virus. Tenofovir and entecavir are often preferred due to their potent antiviral activity and low rates of drug resistance. Additionally, pegylated interferon alfa-2a has been approved and is used for its immunomodulatory effects, which help in achieving sustained virologic response. These treatments aim to reduce HBV DNA levels, normalize liver enzymes, and promote seroconversion of hepatitis B e antigen (HBeAg).

What other types of research exist?

Promising novel alternatives to GSK3228836 for Hepatitis B treatment include RO7062931, an N-acetylgalactosamine-conjugated single-stranded oligonucleotide targeting HBV RNA, and GSK3389404 (Bepirovirsen), an antisense oligonucleotide targeting pregenomic and mRNA transcripts of HBV. Both have shown potential in clinical trials, with RO7062931 demonstrating targeted liver delivery and GSK3389404 showing dose-dependent HBsAg reductions.

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Virus Therapy

Long-Term Follow-Up for GSK3228836 in Hepatitis B

Phase 2

Recruiting

Research Sponsored by GlaxoSmithKline

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants who have previously received at least one dose of GSK3228836 and achieved SVR (defined as HBsAg and HBV DNA < lower limit of quantification (LLOQ) from end of previous investigational treatment until the End of study (EoS) visit in the previous treatment study (complete responder)

Capable of giving signed informed consent

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from primary endpoint assessment in the previous gsk3228836 study up to end of study (month 33)

Awards & highlights

Summary

This trial is checking the duration of benefits for people who previously took the medication GSK3228836 and showed improvement. No new treatment will be given during this study.

Who is the study for?

This trial is for people who have had Hepatitis B and were previously treated with GSK3228836, achieving full or partial virus control. They must be able to stop their current antiviral meds as per the study's schedule and give informed consent. Those in other HBV studies or with conditions that make participation risky can't join.

What is being tested?

The study isn't testing a new treatment; instead, it's checking how long the effects of GSK3228836 last in patients who've already taken it. It looks at whether they maintain low levels of hepatitis B surface antigen (HBsAg) and DNA without further doses.

What are the potential side effects?

Since no additional GSK3228836 will be given in this follow-up study, there are no direct side effects being tested. However, participants' health will be monitored for any late-occurring effects from their previous treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I've had a successful treatment with GSK3228836 for hepatitis B.

Select...

I am able to understand and sign the consent form.

Select...

I have had GSK3228836 before and it partially worked for me.

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I am willing to stop my current NA treatment if required by the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from primary endpoint assessment in the previous gsk3228836 study up to end of study (month 33)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from primary endpoint assessment in the previous gsk3228836 study up to end of study (month 33)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from primary endpoint assessment in the previous gsk3228836 study up to end of study (month 33) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Time from achieving SVR in previous GSK3228836 treatment study to loss of SVR (1st occurrence of either hepatitis B surface antigen or hepatitis B virus deoxyribonucleic acid [DNA] reversion, or 1st use of any rescue medication)-NA naïve participants

Side effects data

From 2022 Phase 2 trial • 457 Patients • NCT04449029

45%

Injection site erythema

25%

Pyrexia

24%

Injection site pruritus

22%

Alanine aminotransferase increased

21%

Headache

19%

Injection site pain

16%

Injection site discolouration

15%

Injection site bruising

13%

Aspartate aminotransferase increased

10%

Fatigue

10%

Injection site induration

10%

Myalgia

10%

Rash

10%

Injection site swelling

Injection site discomfort

COVID-19

Injection site haematoma

Complement factor C3 decreased

Complement factor C4 decreased

Back pain

Nausea

Dizziness

Pruritus

Diarrhoea

Antineutrophil cytoplasmic antibody positive

Malaise

Upper respiratory tract infection

Urticaria

Pain in extremity

Abdominal pain upper

Platelet count decreased

Arthralgia

Haematuria

Oropharyngeal pain

Neutropenia

Abdominal pain

Chills

Influenza like illness

Decreased appetite

Flank pain

Muscular weakness

Erythema

Pharyngitis

Creatinine renal clearance decreased

Injection site nodule

Pain

Iron deficiency anaemia

Thrombocytopenia

Abdominal distension

Non-cardiac chest pain

Herpes simplex

Influenza

Nasopharyngitis

C-reactive protein increased

Insomnia

Cough

Muscle twitching

Abdominal pain lower

Constipation

Nail injury

Skin abrasion

Lymph node pain

Thrombocytosis

Abdominal discomfort

Gastrointestinal sounds abnormal

Feeling abnormal

Hyperthermia

Vaccination complication

Swelling

Hepatic function abnormal

Blood bilirubin increased

Furuncle

Hepatitis B

Infection

Oral herpes

Oral infection

Complement factor abnormal

Complement factor increased

Protein urine present

Epicondylitis

Eye injury

Polydipsia

Joint swelling

Dysgeusia

Hypoaesthesia

Lethargy

Nephrolithiasis

Adenomyosis

Rhinorrhoea

Petechiae

Rash maculo-papular

Rash pruritic

COVID-19 pneumonia

Coagulopathy

Gastrooesophageal reflux disease

Cellulitis

Neoplasm skin

Spinal column injury

Increased tendency to bruise

Atrial fibrillation

Palpitations

Supraventricular extrasystoles

Tachycardia

Eye pain

Periorbital swelling

Catarrh

Aphthous ulcer

Acne

Gingival bleeding

Haemorrhoidal haemorrhage

Asthenia

Rash macular

Injection site anaesthesia

Injection site warmth

Gallbladder polyp

Hepatitis acute

Hypertransaminasaemia

Food allergy

Seasonal allergy

Neutrophil count decreased

Herpes zoster

Parotitis

Animal bite

Contusion

Sunburn

Activated partial thromboplastin time prolonged

Blood alkaline phosphatase increased

Muscle spasms

Musculoskeletal pain

Musculoskeletal stiffness

Osteoarthritis

Leiomyoma

Dysuria

Dysmenorrhoea

Epistaxis

Dermatitis

Dermatitis allergic

Nail bed bleeding

Umbilical erythema

Hypertension

Ear pain

Vaginal infection

100%

80%

60%

40%

20%

Study treatment Arm

Placebo for 12 WK + GSK3228836 for 12 WK (on NA Therapy)

GSK3228836 for 12+12 WK (Not on NA Therapy)

GSK3228836 for 12 WK + Placebo for 12 WK (on NA Therapy)

GSK3228836 for 24 WK (Not on NA Therapy)

GSK3228836 for 12 WK + Placebo for 12 WK (Not on NA Therapy)

Placebo for 12 WK + GSK3228836 for 12 WK (Not on NA Therapy)

GSK3228836 for 24 Weeks (WK) (on NA Therapy)

GSK3228836 for 12+12 WK (on NA Therapy)

Trial Design

2Treatment groups

Experimental Treatment

Group I: Nucleos(t)ide analogue (NA) naïve participantsExperimental Treatment1 Intervention

Participants who have not received NA therapy during the parent study. No study treatment will be administered in this study.

Group II: NA controlled participantsExperimental Treatment1 Intervention

Participants who entered the parent study on stable NA therapy and remained on NA therapy for the duration of the treatment and follow-up periods. NA cessation at 3 months. No study treatment will be administered in this study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

GSK3228836

2020

Completed Phase 2

~610

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Hepatitis B, such as nucleos(t)ide analogs like entecavir and tenofovir, work by inhibiting the viral polymerase enzyme, which is crucial for viral DNA replication. This suppression of viral replication helps reduce the viral load in the patient's body, thereby limiting liver damage and reducing the risk of liver cancer. Investigational agents like GSK3228836 target HBV RNA, leading to reduced production of viral proteins, which may enhance the immune system's ability to control the virus. Understanding these mechanisms is vital for patients as it highlights the importance of these treatments in managing the disease and preventing severe complications.

Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy.Replication of clinical hepatitis B virus isolate and its application for selecting antiviral agents for chronic hepatitis B patients.