RO7565020 for Chronic Hepatitis B

No longer recruiting at 17 trial locations

Overseen By Reference Study ID Number: BP44118 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Must be taking: NUC monotherapy

Must not be taking: Systemic anti-neoplastic

Disqualifiers: Liver cirrhosis, Hepatocellular carcinoma, others

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RO7565020 to assess its safety and behavior in the body. It targets individuals with chronic hepatitis B (a long-term liver infection) who are currently managing their condition with specific medications. Participants will receive either the new treatment or a placebo (a look-alike substance with no active ingredients) to compare results. Ideal candidates for this trial have had hepatitis B for at least six months, have been on specific medications for at least a year, and maintain a healthy body weight. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop all current medications. However, if you are a healthy volunteer, you must not have used any treatment within 2 weeks or 5 half-lives before the first dose. If you have chronic hepatitis B, you must continue your NUC monotherapy.

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

Research has shown that treatments like RO7565020, part of a group called nucleos(t)ide analogues, are usually well-tolerated. These treatments effectively reduce virus levels, indicating their safety. So far, studies have not identified any major side effects for RO7565020, suggesting it is relatively safe for people with chronic hepatitis B. However, as this is its first test in humans, ongoing trials will provide more detailed information about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic hepatitis B?

Unlike the standard treatments for chronic hepatitis B, which often include nucleos(t)ide analogs (NUCs) that work by suppressing viral replication, RO7565020 is unique because it represents a new class of medication with a different mechanism of action. Researchers are excited about RO7565020 because it targets the virus in a novel way, potentially offering improved outcomes for patients who do not respond well to existing therapies. This innovative approach could lead to a more effective strategy for managing chronic hepatitis B, which remains a significant global health challenge.

What evidence suggests that this trial's treatments could be effective for chronic hepatitis B?

Research shows that RO7565020, a treatment under study for chronic hepatitis B, is a monoclonal antibody. This means it targets specific proteins in the body to combat the virus. Early studies suggest it might help remove the virus, a major goal in treating hepatitis B. For instance, after 48 weeks, some patients in these studies had a 10% clearance rate of the virus. Although this number might seem small, it is promising for a new treatment. More research is needed, but these early results are encouraging. ^{1 2 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for healthy adults or those with chronic hepatitis B (CHB) who have a BMI of 18-32 kg/m^2. CHB participants must have been positive for HBsAg for at least 6 months and on NUC therapy for over a year without signs of advanced liver disease. People with cirrhosis, suspected cancer, or other significant diseases are excluded.

Inclusion Criteria

Healthy volunteers: Body mass index (BMI) between 18 and 32 kg/m^2

CHB participants: CHB infection (HBsAg-positive for >/= 6 months), On NUC (ETV, TAF, or TDF) monotherapy for >/= 12 months, Liver biopsy, FibroScan, or equivalent test within the past 6 months demonstrating liver disease consistent with chronic HBV infection without evidence of bridging fibrosis or cirrhosis, BMI between 18 and 32 kg/m^2

Exclusion Criteria

I am healthy with no significant diseases or treatments that could affect the study.

I have liver issues not solely due to hepatitis B, or I've had cancer or immune treatments recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single and/or multiple doses of RO7565020 to investigate safety, tolerability, pharmacokinetics, and pharmacodynamics

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NUC treatment
• Placebo
• RO7565020

Trial Overview

The study tests RO7565020's safety and effects in humans compared to a placebo. It's the first time this drug is being tried in people. The trial will gradually increase doses to find safe levels and see how the body reacts over single or multiple doses in both healthy individuals and those with suppressed CHB.

How Is the Trial Designed?

Group I: RO7565020 Experimental Treatment 2 Interventions

Group II: Placebo Placebo Group 1 Intervention

NUC treatment is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Nucleos(t)ide analogue for:

• Chronic hepatitis B
• HIV infection
• Herpes simplex virus infection

Approved in United States as Nucleos(t)ide analogue for:

• Chronic hepatitis B
• HIV infection
• Herpes simplex virus infection

Approved in Canada as Nucleos(t)ide analogue for:

• Chronic hepatitis B
• HIV infection
• Herpes simplex virus infection

Approved in Japan as Nucleos(t)ide analogue for:

• Chronic hepatitis B
• HIV infection
• Herpes simplex virus infection

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

In a study of 102 patients with chronic hepatitis B, persistence rates for nucleos(t)ide analogues (NUCs) decreased over time, with a more rapid decline observed between weeks 48 and 96.

Entecavir demonstrated the highest persistence rates among the five NUCs studied, suggesting that medications with a high genetic barrier, like entecavir and tenofovir, are more effective in maintaining treatment adherence in the initial stages of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence profile to nucleos(t)ide analogue treatment for patients with chronic hepatitis B. Borrego Izquierdo, Y., Gómez Fernández, E., Monje Agudo, P., et al.[2022]

In a study of 600 treatment-naïve chronic hepatitis B patients over 3 years, those treated with entecavir (ETV) showed a significantly lower rate of treatment modification (9.0%) compared to those on telbivudine (38.8%) and lamivudine (54.2%).

Patients on ETV also demonstrated a higher adherence rate (>90%) at year 3 (90.8%), indicating that ETV may be a more effective and reliable treatment option for chronic hepatitis B compared to other nucleos(t)ide analogs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher adherence with 3-year entecavir treatment than lamivudine or telbivudine in treatment-naïve Taiwanese patients with chronic hepatitis B. Chien, RN., Peng, CY., Kao, JH., et al.[2014]

Lamivudine treatment significantly reduces the risk of developing hepatocellular carcinoma (HCC) by 51% compared to no treatment, based on a study of 3,306 patients.

Despite the reduction in HCC risk with antiviral treatment, the incidence remains at 1.3 cases per 100 person-years, indicating the need for ongoing surveillance, especially in older patients and those with cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis: the impact of oral anti-viral agents on the incidence of hepatocellular carcinoma in chronic hepatitis B. Singal, AK., Salameh, H., Kuo, YF., et al.[2022]

In a study of 101 patients with chronic hepatitis B treated for over 3 years, entecavir and tenofovir showed over 95% effectiveness in achieving virologic and biochemical responses, with high rates of HBeAg seroconversion (93% for entecavir and 67% for tenofovir).

Long-term treatment with these nucleos(t)ide analogues not only reduced liver fibrosis significantly but also had a cumulative virologic resistance rate of 0% for tenofovir and only 3.1% for entecavir, while telbivudine had a much higher resistance rate of 43.5% and was associated with myopathy in 13% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of long-term therapy with nucleos(t)ide analogues in chronic hepatitis B. Ibragimov, EK., Abdurakhmanov, DT., Rozina, TP., et al.[2019]

In a study of 72 non-cirrhotic HBeAg-negative chronic hepatitis B patients, 51.7% were re-treated after discontinuing nucleos(t)ide analogs, with a median relapse time of 11 months, indicating a significant risk of relapse after treatment cessation.

Re-treatment was more common in males and those treated with tenofovir or entecavir, with higher baseline hepatitis B virus DNA levels (≥405,000 IU/L) being a key predictor for the need for re-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discontinuation of Nucleos(t)ide Analog treatment in HBeAg-Negative Non-Cirrhotic Chronic Hepatitis B Patients: Real-Life Data of 20 Years. Mete, B., Kaya, SY., Kaya, A., et al.[2023]

In a study of 77 chronic hepatitis B patients who discontinued nucleos(t)ide analogue therapy after achieving viral suppression, no significant benefits were observed from stopping treatment, particularly in those with severe fibrosis.

For patients with mild to moderate fibrosis, stopping antiviral therapy did not lead to adverse outcomes, indicating that careful monitoring is essential when considering treatment cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Cessation of Antiviral Therapy in Chronic Hepatitis B: A Retrospective Cohort Study. Ergen, P., Isik, B., Arslan, F., et al.[2022]

In a study of 10,192 patients with chronic hepatitis B who stopped nucleos(t)ide analogue therapy, severe hepatitis flares with hepatic decompensation occurred in 1.8% of patients over a median follow-up of 2.2 years, indicating a notable risk after treatment cessation.

Key risk factors for these severe flares included older age, the presence of cirrhosis, manifestations of portal hypertension, and being male, suggesting that careful monitoring is needed for these high-risk groups when considering stopping NUC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe hepatitis B flares with hepatic decompensation after withdrawal of nucleos(t)ide analogues: A population-based cohort study. Hsu, YC., Lin, YH., Lee, TY., et al.[2023]

In a study of 28 patients undergoing nucleos(t)ide analogue (NUC) treatment for chronic hepatitis B, significant reductions in HBV DNA integration and hepatocyte clonal expansion were observed over 10 years, indicating a potential mechanism for lowering hepatocellular carcinoma (HCC) risk.

After one year of NUC treatment, there was a notable decrease in HBV integration frequency and hepatocyte clone size, with continued reductions observed at year 10, suggesting that long-term NUC therapy may be beneficial in preventing HCC beyond just suppressing the virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Antiviral Treatment on Hepatitis B Virus Integration and Hepatocyte Clonal Expansion. Chow, N., Wong, D., Lai, CL., et al.[2023]

Oral nucleos(t)ide analogues (NUCs), such as entecavir (ETV) and tenofovir disoproxil fumarate (TDF), are effective first-line treatments for chronic hepatitis B (CHB) with a generally favorable long-term safety profile, although TDF may cause renal and bone toxicity in some patients.

Tenofovir alafenamide (TAF) has been introduced to mitigate the renal and bone side effects associated with TDF, but more research is needed to determine the comparative effectiveness of TDF and ETV in reducing the risk of hepatocellular carcinoma (HCC).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of current antiviral drugs for chronic hepatitis B. Masetti, C., Pugliese, N., Aghemo, A., et al.[2022]

Older nucleoside analogues like adefovir and tenofovir disoproxil fumarate (TDF) have been associated with nephrotoxicity, but real-life data show similar risks of renal failure compared to newer treatments.

The newly approved tenofovir alafenamide (TAF) offers improved safety for renal and bone health compared to TDF, making it a preferable option for patients with chronic hepatitis B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review article: long-term safety of oral anti-viral treatment for chronic hepatitis B. Wong, GL., Seto, WK., Wong, VW., et al.[2019]

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are generally well tolerated in treating chronic hepatitis B, with no significant renal toxicity or lactic acidosis reported in clinical trials, although some real-world cases of ETV-related lactic acidosis and TDF-related renal impairment have emerged.

Monitoring kidney function (eGFR and phosphorus levels) before and during treatment is crucial to minimize potential renal toxicity from NUCs, and there is a need for standardized definitions and early markers of renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review article: long-term safety of nucleoside and nucleotide analogues in HBV-monoinfected patients. Lampertico, P., Chan, HL., Janssen, HL., et al.[2018]

Adefovir dipivoxil (ADV) is effective for treating chronic hepatitis B but can cause nephrotoxicity, particularly at a daily dose of 10 mg, leading to issues like hypophosphatemia and elevated creatinine levels.

Regular monitoring of renal function is crucial for patients on ADV to adjust dosages and prevent kidney damage, as some patients may experience reversible renal toxicity or even Fanconi syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug safety evaluation of adefovir in HBV infection. Viganò, M., Lampertico, P., Colombo, M.[2013]

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A clinical trial to look at the safety and effectiveness of RO7565020 at different doses and how the body processes RO7565020 in healthy people and those with ...

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Roche Discontinues 4 Hepatitis B Drug Pipelines

After 24 weeks of post-treatment follow-up, the HBsAg clearance rates were 7%, 12%, and 23%, respectively, and after 48 weeks, the rates were 10 ...

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Safety, tolerability, pharmacokinetics, and pharmacodynamics of ...

Safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7565020, a novel monoclonal antibody that targets the hepatitis B surface antigen: results ...