VIR-2218 + Peginterferon Alfa-2a for Chronic Hepatitis B

Overseen By Camelia Achondo

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must not be taking: Theophylline, Methadone

Disqualifiers: Pregnancy, HIV, Cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2223

Duration: 36 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two medications, VIR-2218 (an experimental treatment) and peginterferon (a type of interferon therapy), to find better treatments for chronic hepatitis B, a liver infection that can lead to serious issues like liver cancer. The study targets individuals with mild or inactive hepatitis B. Those with low viral levels and no severe liver problems might be suitable for this trial. Participants will receive injections over several months and undergo various tests to monitor liver health. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important advancements in hepatitis B treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using oral theophylline, methadone, or have had any treatment for HBV in the last 24 weeks.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of VIR-2218 and peginterferon has been tested for safety in people with chronic hepatitis B. In earlier studies, these treatments were generally well-tolerated, with most participants not experiencing serious problems. VIR-2218, whether used alone or with peginterferon, did not raise major safety concerns.

Some participants experienced side effects, usually mild to moderate. The most common side effects included headaches, fatigue, and injection site reactions. These are typical for such treatments and are not considered severe.

This ongoing research is at a stage where treatments are tested for both safety and efficacy. While there is some evidence that the treatments are safe, more information is needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of VIR-2218 and Peginterferon Alfa-2a for chronic hepatitis B because it represents a novel approach compared to traditional treatments like antiviral medications, which primarily aim to suppress the virus. VIR-2218 is a small interfering RNA (siRNA) that targets the hepatitis B virus (HBV) RNA, potentially reducing the virus's ability to replicate and spread. This mechanism is different from current options, and when combined with Peginterferon Alfa-2a, which boosts the immune system's response against HBV, it may offer a more comprehensive attack on the virus. This dual approach might lead to a functional cure for some patients, which is a significant step forward from simply managing the disease.

What evidence suggests that VIR-2218 and peginterferon could be effective for chronic hepatitis B?

Studies have shown that VIR-2218 can significantly reduce hepatitis B surface antigen (HBsAg) levels, achieving decreases of 2.7-3.1 log10 IU/mL when combined with VIR-3434. This reduction lowers the virus amount in the body. Peginterferon alfa-2a, another treatment option, has effectively reduced the virus's DNA levels, with some patients showing no detectable virus after treatment. It also enhances the body's ability to fight the virus. This trial studies VIR-2218 and Peginterferon alfa-2a together to reduce the virus and improve liver health in people with chronic hepatitis B. ^{6 7 8 9 10}

Who Is on the Research Team?

Marc G Ghany, M.D.

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Are You a Good Fit for This Trial?

Adults aged 18 to 65 with mild or inactive chronic hepatitis B can join this trial. They must have specific levels of HBV DNA and antigens, normal liver enzyme levels, and agree to use effective contraception. Those who are pregnant, breastfeeding, have other liver infections or diseases like cirrhosis or cancer, recent treatments for HBV, certain medical conditions or drug use that could interfere with the study cannot participate.

Inclusion Criteria

You have tested negative for the hepatitis B e antigen.

Your Hepatitis B Virus DNA levels have been less than 10,000 IU/mL on two separate occasions at least 24 weeks apart, with the second measurement taken at time of screening.

Your alanine transaminase (ALT) level is no greater than two times the upper limit of normal for your gender, as determined by at least two tests taken 24 weeks apart, with the most recent one being prior to screening.

Exclusion Criteria

I do not have other liver conditions like hemochromatosis or alcoholic liver disease.

Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study

I am allergic to specific genetic therapies or interferon treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive VIR-2218 injections once a month for 3 months, followed by combination treatment with peginterferon alfa-2a weekly for 3 months, and then peginterferon alfa-2a alone weekly for another 3 months

36 weeks

Monthly visits for VIR-2218, weekly visits or self-administration for peginterferon

Follow-up

Participants are monitored for safety and effectiveness after treatment

84 weeks

Visits every 4 to 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Peginterferon Alfa-2a
• VIR-2218

Trial Overview The trial is testing VIR-2218 and peginterferon alfa-2a in people with chronic hepatitis B over a period of more than two years. Participants will receive monthly injections of VIR-2218 for six months and weekly shots of peginterferon for six months at home or in the clinic. The study includes hospital stays for liver biopsies and other tests.

How Is the Trial Designed?

Group I: Single arm, open label Experimental Treatment 1 Intervention

open label

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study involving 2,940 patients with HCV, high-dose peginterferon alfa-2a (360 μg/week) did not significantly increase serious adverse events or treatment discontinuations compared to the standard dose (180 μg/week) during the first 12 weeks of treatment.

While more patients on the high-dose experienced weight loss as an adverse event (7.7% vs. 3.3%), the overall safety profile was similar, indicating that high doses can be managed effectively without increasing safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of standard- vs. high-dose peginterferon alfa-2a plus standard-dose ribavirin in HCV genotype 1/4 patients: pooled analysis from 5 randomized studies. Marcellin, P., Roberts, SK., Reddy, KR., et al.[2018]

In a study of 57 patients with chronic hepatitis B who did not achieve satisfactory results from entecavir treatment, those who received peginterferon alfa-2a therapy had significantly higher rates of HBeAg clearance (40.7% vs. 16.7%) and seroconversion (37.0% vs. 13.3%) after 48 weeks compared to those who continued on entecavir.

The peginterferon alfa-2a group also showed a significant reduction in HBsAg levels, indicating a potential benefit in managing chronic hepatitis B in patients who previously did not respond well to entecavir.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[HBeAg seroconversion achieved by sequential peginterferon alfa-2a therapy in chronic hepatitis B patients with unsatisfactory end point following entecavir treatment]. Chen, XF., Chen, XP., Ma, XJ., et al.[2018]

In a study of 298 inactive hepatitis B virus carriers, peginterferon alpha (peg-IFN-α) monotherapy led to a high rate of hepatitis B surface antigen (HBsAg) clearance at 72 weeks, with 47.9% achieving clearance compared to only 1.9% in the control group.

The treatment was generally well tolerated, with only five participants discontinuing due to adverse events, indicating that peg-IFN-α is a safe option for managing inactive HBV carriers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of peginterferon alpha monotherapy in Chinese inactive chronic hepatitis B virus carriers. Wu, F., Lu, R., Liu, Y., et al.[2021]

In a study of 218 treatment-naive Chinese patients with HBeAg-positive chronic hepatitis B, the combination of pegylated interferon alfa-2a and entecavir did not show superior efficacy compared to peg-IFN monotherapy, with similar rates of HBeAg seroconversion across all treatment groups.

All treatment groups achieved significant reductions in HBeAg levels, but while the ETV add-on showed greater reductions in hepatitis B virus DNA during treatment, these effects were not sustained after treatment ended, indicating that the optimal treatment strategy remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, open-label clinical study of combined pegylated interferon Alfa-2a (40KD) and entecavir treatment for hepatitis B "e" antigen-positive chronic hepatitis B. Xie, Q., Zhou, H., Bai, X., et al.[2022]

In a study of 102 chronic hepatitis B patients treated with peginterferon-alpha 2a, both HBeAg-positive and HBeAg-negative groups showed similar rates of response to the therapy, indicating its efficacy across different patient types.

For HBeAg-positive patients, higher serum ALT levels (greater than 3 times the upper limit of normal) and more severe liver inflammation (grades G3 and G4) were associated with better therapeutic responses, suggesting these factors could help predict treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Responses of peginterferon-alpha 2a antiviral therapy in chronic hepatitis B patients]. Zhong, RX., Lai, CY., Liang, D., et al.[2018]

In a study of 205 HBeAg-positive chronic hepatitis B patients treated with peginterferon alfa, specific IL28B genotypes were found to significantly influence the likelihood of achieving HBeAg seroconversion, with an odds ratio of 3.16 for the AA genotype compared to AG/GG.

The IL28B genotype was also associated with long-term outcomes, showing a 2.14 times higher probability of HBeAg seroconversion and a 3.47 times higher chance of hepatitis B surface antigen clearance for the AA genotype, indicating its potential role as a biomarker for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polymorphisms near IL28B and serologic response to peginterferon in HBeAg-positive patients with chronic hepatitis B. Sonneveld, MJ., Wong, VW., Woltman, AM., et al.[2023]

In a study of 35 HBeAg-negative, genotype D-naive patients treated with PEG-IFN α-2a for 48 weeks, a sustained virologic response (SVR) was achieved in 23% of patients at a HBV DNA cutoff of <400 copies/ml, and in 57% at a more sensitive cutoff of <20,000 copies/ml.

Key predictors for achieving SVR included low body weight, high alanine aminotransferase (ALT) levels, low HBV DNA, and low triglyceride levels, suggesting that these factors could help identify patients more likely to respond to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of peginterferon α-2a and predictors of response in HBeAg-negative, genotype D-naive patients. Al-Ashgar, HI., Khan, MQ., Aljumah, A., et al.[2021]

In a study of 72 patients with chronic hepatitis B, PEG-IFN alpha-2a demonstrated significantly higher rates of HBeAg negative cases and lower HBV DNA levels compared to the control group receiving standard interferon alpha after 48 weeks of treatment.

PEG-IFN alpha-2a not only effectively inhibited HBV replication but also showed lasting effects after treatment, with no significant changes in liver inflammation or fibrosis, and was well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pegylated interferon alpha 2a in treating chronic hepatitis B patients]. Tian, YL., Zhao, W., Shen, L., et al.[2018]

A new scoring system was developed to predict the likelihood of hepatitis B surface antigen (HBsAg) clearance in patients with chronic hepatitis B (CHB) treated with peginterferon alfa-2b, based on four key clinical variables: age, baseline HBsAg level, HBsAg level decline at week 12, and alanine aminotransferase ratio at week 12.

The scoring system demonstrated high sensitivity (86.49%) and specificity (72.16%), effectively categorizing patients into different likelihoods of achieving HBsAg clearance, which can aid in clinical decision-making for CHB treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A simple-to-use score system for predicting HBsAg clearance to peginterferon alfa-2b in nucleoside analogs-experienced chronic hepatitis B patients. Song, K., Zeng, D., Zheng, Y., et al.[2023]

In a study of 160 HBeAg-negative chronic hepatitis B patients treated with pegylated interferons, 25% achieved a sustained virologic response (SVR), indicating the treatment's efficacy.

Key predictors for achieving SVR included a decline of 1 log10 IU/mL in viral load after the first month and a serum HBV DNA level below 2,000 IU/mL by the third month of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of response to pegylated interferon treatment in HBeAg-negative patients with chronic hepatitis B. Guclu, E., Tuna, N., Karabay, O., et al.[2018]

In a study of 85 HBeAg-positive chronic hepatitis B patients with poor response to peginterferon alfa-2a, adding adefovir significantly improved sustained virological response rates from 31.4% to 73.5%.

Patients receiving adefovir also showed higher rates of HBeAg loss (55.9% vs. 19.6%) and seroconversion (41.2% vs. 13.7%), indicating that adefovir enhances the effectiveness of peginterferon therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained efficacy of adefovir add-on therapy in chronic hepatitis B patient with a poor virological response to peginterferon alfa. Wang, YX., Zheng, SM., Zhang, Y., et al.[2018]

In a study of 43 HBeAg-positive chronic hepatitis B patients who had previously not responded to other treatments, peginterferon alpha-2a demonstrated efficacy with an HBeAg seroconversion rate increasing from 4.65% at the end of treatment to 11.62% after 24 weeks of follow-up.

The treatment also achieved viral suppression below 100,000 copies/mL in 23.25% of patients at the end of treatment, with ALT normalization occurring in 20.9% of patients, indicating that peginterferon alpha-2a can be a beneficial option for difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of peginterferon alpha-2a (40KD) in HBeAg-positive chronic hepatitis B patients. Caruntu, FA., Streinu-Cercel, A., Gheorghe, LS., et al.[2018]

Citations

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Safety and efficacy of 48-week pegylated interferon-α-2b ... Forty-two patients achieved undetectable serum HBV DNA at 48 weeks post-therapy. HBsAg level was significantly reduced at 48 weeks post-therapy ...

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Predicting clinical outcomes in chronic hepatitis B patients ... This study provided predictive formulas for clinical cure, offering valuable insights for CHB treatment. PegIFN and NAs exhibited efficacy.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1201971220303489

Clinical characteristics of chronic hepatitis B cured by ... The average Peg-IFN treatment time was 102.6 weeks, suggesting that the combination therapy for CHB clinical cure is generally more than 96 weeks. However, most ...

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Peginterferon Alfa-2a, Lamivudine, and the Combination ... Peginterferon alfa-2a offers superior efficacy over lamivudine, on the basis of HBeAg seroconversion, HBV DNA suppression, and HBsAg seroconversion.

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Safety and efficacy of two-step peginterferon α-2a ... Patients with HBeAg-negative chronic hepatitis B showed a ratio of 30% (3/10) HBsAg loss and 20% (2/10) of HBsAg seroconversion after 48 weeks of two-step ...

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VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in ... We aimed to evaluate the safety and antiviral activity of VIR-2218 with and without pegylated interferon-alpha-2a treatment in participants with chronic HBV.

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VIR-2218 and Peginterferon Alfa-2a for Chronic Hepatitis B 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.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04412863

Study of VIR-2218 With or Without Pegylated Interferon ... This is a phase 2 study in which subjects with chronic hepatitis B virus (HBV) infection will receive VIR-2218 alone or in combination with pegylated interferon ...

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VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in ... This study evaluates the safety and antiviral activity of several treatment regimens of VIR-2218 in combination with pegylated interferon-alfa-2a compared with ...

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VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in ... The results of this phase 2 study support further development of VIR-2218 as a potential therapy for patients with chronic HBV infection.