Epclusa for Chronic Hepatitis C

Overseen By Alaina Magnani

Age: 18+

Sex: Any

Trial Phase: Phase 4

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

Must be taking: Hepatitis C drugs

Must not be taking: Acid reducers, Antiarrhythmics, Anticancer, others

Disqualifiers: Pregnancy, HIV, Solid organ transplant, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 32

121 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Chronic hepatitis C infects the liver. It may scar the liver. This is called cirrhosis and may lead to liver cancer or death. Current chronic hepatitis C treatments cure most people. But some keep getting complications even after it is cured. Researchers want to study why. Objective: To study the course and complications of liver disease after cure of hepatitis C infection. Eligibility: Adults 18 years and older infected with chronic hepatitis C virus who were never treated or were treated and not cured and those who were cured Design: Participants will be screened with: Blood and urine tests Questionnaires Liver ultrasound Fibroscan. A probe vibrates the liver, testing stiffness. In Phase 1, people with chronic hepatitis C will: Have a 3-day hospital admission to repeat some screening tests and have a liver biopsy. A small piece of liver is removed by needle passed through the skin. Take 1 tablet containing 2 hepatitis C drugs once a day for 12 weeks. Repeat some blood tests at 3 visits in those 12 weeks while on treatment, then 4 additional visits in the next 24 weeks with more blood work collected. Phase 1 participants who test negative for hepatitis C and all other eligible participants will enter Phase 2. Phase 2 participants will have a visit every 24 weeks for 10 years. These may include: Repeats of screening tests Questionnaires Scans Stool tests Chest x-ray Heart function test Endoscopy. A tube guides a camera into the upper digestive system. At about 5 years, participants will have another liver biopsy. Some participants will give separate consent for genetic testing and a special blood procedure....

Do I need to stop my current medications to join the trial?

You may need to stop certain medications before joining the trial. Specifically, you cannot use medications that are contraindicated with sofosbuvir/velpatasvir within 21 days before starting the trial, except for proton pump inhibitors, which can be taken up to 7 days before. Please consult with the trial team for specific guidance on your medications.

What data supports the effectiveness of the drug Epclusa for treating chronic hepatitis C?

Research shows that Epclusa, a combination of sofosbuvir and velpatasvir, is highly effective in treating various types of hepatitis C, including in patients with liver transplants and those co-infected with HIV. It has been shown to produce high cure rates and improve patient-reported outcomes. ^{1 2 3 4 5}

Is Epclusa (sofosbuvir/velpatasvir) safe for humans?

Epclusa (sofosbuvir/velpatasvir) is generally safe for humans, with common side effects being headache, fatigue, and nausea. Serious side effects were rare and not considered related to the treatment. ^{1 6 7 8 9}

How is the drug Epclusa unique for treating chronic hepatitis C?

Epclusa is unique because it is a once-daily, single-tablet regimen that works for all genotypes of hepatitis C, making it versatile for treating different strains of the virus. It combines two active ingredients, sofosbuvir and velpatasvir, which target different parts of the virus's replication process, and is effective even in patients with cirrhosis or those who have had a liver transplant. ^{1 3 5 10 11}

Research Team

Marc G Ghany, M.D.

Principal Investigator

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

Eligibility Criteria

Adults over 18 with chronic hepatitis C, either untreated or previously treated but not cured. They must have a liver biopsy showing chronic hepatitis and meet specific health criteria like normal bilirubin levels and platelet counts. Pregnant women, those unable to use contraception, people with other significant diseases or conditions that could interfere with the study drug's absorption are excluded.

Inclusion Criteria

I had successful hepatitis treatment with medication and a liver biopsy before treatment.

I have either never been treated or have not responded to previous hepatitis treatments.

I have had chronic hepatitis C confirmed by a test more than 6 months ago.

Exclusion Criteria

I have previously been treated with an NS5a agent.

I do not have major health issues that could affect my participation in the study.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase 1 Treatment

Participants receive 12 weeks of therapy with sofosbuvir/velapatasvir (Epclusa) and undergo various tests including liver biopsy

12 weeks

3 visits (in-person) during treatment

Phase 1 Follow-up

Participants are monitored for sustained virological response (SVR) with additional blood tests

24 weeks

4 visits (in-person)

Phase 2 Long-term Follow-up

Participants are followed every 24 weeks for 10 years to monitor liver-related outcomes and complications

480 weeks

Visits every 24 weeks

Treatment Details

Interventions

• Epclusa

Trial Overview The trial is testing Epclusa in individuals who've achieved sustained virological response after direct-acting antiviral agents for hepatitis C. It includes initial hospital admission for tests, daily medication for 12 weeks followed by blood tests, then biannual visits for up to 10 years including various screenings and procedures.

Participant Groups

Group I: Phase I Experimental Treatment 1 Intervention

Phase I treatment

Group II: Phase II after Phase I Active Control 1 Intervention

Participants who achieved SVR12 in Phase I

Group III: Phase II without Phase I Active Control 1 Intervention

Participants who achieved SVR 24 previously

Epclusa is already approved in European Union, United States for the following indications:

Approved in European Union as Epclusa for:

• Chronic hepatitis C

Approved in United States as Epclusa for:

• Chronic hepatitis C

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+

Findings from Research

The sofosbuvir-velpatasvir regimen achieved a high sustained virological response (SVR12) rate of 94.2% in 1277 patients with chronic hepatitis C virus (HCV) infection, indicating its strong efficacy.

Adding ribavirin did not significantly improve SVR12 rates for HCV genotypes 1 and 2, but it did enhance the response for genotype 3 patients, suggesting that ribavirin may be beneficial for specific HCV genotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of sofosbuvir-velpatasvir: A meta-analysis. Ren, XD., Fu, X., He, YQ., et al.[2022]

Sofosbuvir/velpatasvir/voxilaprevir is highly effective for treating hepatitis C virus (HCV) in patients with genotypes 1 through 6 who have previously been treated with an NS5A inhibitor, as shown in the POLARIS-1 study with a 12-week treatment duration.

The treatment is generally safe, with common side effects including headache, fatigue, diarrhea, and nausea, making it a viable option for patients with chronic HCV, especially those with prior exposure to direct-acting antivirals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C. Chahine, EB., Kelley, D., Childs-Kean, LM.[2021]

In a phase 3 study of 111 patients with chronic hepatitis C, 97% achieved a sustained virologic response (SVR12) after 12 weeks of treatment with sofosbuvir-velpatasvir, demonstrating its high efficacy across various HCV genotypes.

The treatment was well tolerated, with a safety profile similar to placebo, and only one patient discontinued due to an adverse event not related to the drug, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deferred treatment with a fixed-dose combination of sofosbuvir-velpatasvir for chronic hepatitis C virus genotype 1, 2, 4 and 6 infection. Asselah, T., Shafran, SD., Bourgeois, S., et al.[2020]

In a phase 2 trial involving 161 patients with hepatitis C, an 8-week treatment regimen of sofosbuvir, velpatasvir, and GS-9857 achieved a sustained virologic response (SVR12) in 100% of treatment-naïve patients with HCV genotype 1 and 3, including those with compensated cirrhosis.

The combination therapy was generally well-tolerated, with common side effects including headache, nausea, and fatigue, indicating a favorable safety profile alongside its high efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the Combination of Sofosbuvir, Velpatasvir, and the NS3/4A Protease Inhibitor GS-9857 in Treatment-Naïve or Previously Treated Patients With Hepatitis C Virus Genotype 1 or 3 Infections. Gane, EJ., Schwabe, C., Hyland, RH., et al.[2021]

The combination of sofosbuvir and velpatasvir (Epclusa®) is a once-daily, single-tablet treatment that has shown very high rates of sustained virological response (SVR12) in adults with chronic hepatitis C virus (HCV) genotypes 1-6, including those with cirrhosis or HIV-1 co-infection, based on phase III ASTRAL trials.

Sofosbuvir/velpatasvir is generally well tolerated with low rates of adverse events, making it a safe and effective treatment option for a wide range of patients with chronic HCV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sofosbuvir/Velpatasvir: A Review in Chronic Hepatitis C. Greig, SL.[2022]

References

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

Safety and efficacy of sofosbuvir-velpatasvir: A meta-analysis. [2022]

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

Patient-reported outcomes in patients co-infected with hepatitis C virus and human immunodeficiency virus treated with sofosbuvir and velpatasvir: The ASTRAL-5 study. [2022]

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

Case Report of Hepatitis C Treatment Success in Male With Decompensated Cirrhosis and Polysubstance Abuse: The Important Role of the Pharmacist in Active Care Coordination. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Eight weeks of sofosbuvir/velpatasvir for genotype 3 hepatitis C in previously untreated patients with significant (F2/3) fibrosis. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients. [2022]

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

Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C. [2021]

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

Deferred treatment with a fixed-dose combination of sofosbuvir-velpatasvir for chronic hepatitis C virus genotype 1, 2, 4 and 6 infection. [2020]

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

Sofosbuvir/Velpatasvir: The First Pangenotypic Direct-Acting Antiviral Combination for Hepatitis C. [2018]

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

Efficacy of the Combination of Sofosbuvir, Velpatasvir, and the NS3/4A Protease Inhibitor GS-9857 in Treatment-Naïve or Previously Treated Patients With Hepatitis C Virus Genotype 1 or 3 Infections. [2021]

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

Sofosbuvir-velpatasvir-voxilaprevir in adolescents 12 to 17 years old with HCV infection. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Sofosbuvir/Velpatasvir: A Review in Chronic Hepatitis C. [2022]