RO7565020 for Chronic Hepatitis B

Recruiting in Palo Alto (17 mi)

+14 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Hoffmann-La Roche

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called RO7565020 to see if it is safe and how it behaves in the body. It includes healthy people and those with chronic hepatitis B. Researchers aim to understand how the drug moves through and affects the body.

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.

What data supports the idea that RO7565020 for Chronic Hepatitis B is an effective treatment?

The available research shows that oral nucleos(t)ide analogues, which include treatments like RO7565020, are recommended as a first choice for chronic hepatitis B because they are effective at reducing the virus in the body and are considered safe. This suggests that RO7565020 could be effective in managing chronic hepatitis B by keeping the virus under control. ^{1 2 3 4 5}

What safety data is available for RO7565020 treatment in chronic hepatitis B?

The safety profile of nucleos(t)ide analogues, which include treatments like RO7565020, is generally well-tolerated and achieves high rates of viral suppression. Long-term use is common, and while most treatments are safe, some, like adefovir dipivoxil, may cause adverse effects such as nephrotoxicity. Entecavir and tenofovir disoproxil fumarate are preferred first-line agents due to their favorable safety profiles. ^{1 6 7 8 9}

Is the drug RO7565020 a promising treatment for Chronic Hepatitis B?

RO7565020, a type of drug known as a nucleos(t)ide analogue, is promising for treating Chronic Hepatitis B because similar drugs have been effective in managing the disease and reducing virus replication. ^{1 8 10 11 12}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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.

Treatment Details

Interventions

• NUC treatment (Nucleos(t)ide analogue)
• Placebo (Other)
• RO7565020 (Other)

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.

Participant Groups

Group I: RO7565020 Experimental Treatment 2 Interventions

Group II: Placebo Placebo Group 1 Intervention

NUC treatment is already approved in Canada, Japan for the following indications:

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

Findings from Research

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 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]

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]

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 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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Persistence profile to nucleos(t)ide analogue treatment for patients with chronic hepatitis B. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Severe hepatitis B flares with hepatic decompensation after withdrawal of nucleos(t)ide analogues: A population-based cohort study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Safety of current antiviral drugs for chronic hepatitis B. [2022]

4. Turkey pubmed.ncbi.nlm.nih.gov

Outcomes of Cessation of Antiviral Therapy in Chronic Hepatitis B: A Retrospective Cohort Study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of Antiviral Treatment on Hepatitis B Virus Integration and Hepatocyte Clonal Expansion. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Review article: long-term safety of oral anti-viral treatment for chronic hepatitis B. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Review article: long-term safety of nucleoside and nucleotide analogues in HBV-monoinfected patients. [2018]

8. Turkey 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Drug safety evaluation of adefovir in HBV infection. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Meta-analysis: the impact of oral anti-viral agents on the incidence of hepatocellular carcinoma in chronic hepatitis B. [2022]

11. Australia 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. [2014]

12. Russia (Federation) pubmed.ncbi.nlm.nih.gov

Efficacy and safety of long-term therapy with nucleos(t)ide analogues in chronic hepatitis B. [2019]