Sofosbuvir/Velpatasvir for Hepatitis C in Pregnancy

(STORC Trial)

Recruiting at 9 trial locations

Overseen By Leslie Meyn, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Catherine Chappell

Must not be taking: Acid-suppressants, others

Disqualifiers: Cirrhosis, Cardiovascular, Renal, 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: 13

Duration: 12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment for chronic hepatitis C during pregnancy. The researchers aim to determine if the medication Sofosbuvir/Velpatasvir (Epclusa) can effectively treat the virus without affecting the pregnancy. Participants will take one tablet daily for 12 weeks, starting in their second or third trimester. Suitable candidates are pregnant individuals between 20 to 30 weeks of gestation with a confirmed hepatitis C diagnosis. The study will also monitor babies from birth until one year old to assess any effects. As a Phase 4 trial, this research helps to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial requires that if you are taking acid-suppressant medications, you must either stop them during the 12-week treatment or follow specific dosing instructions. Additionally, you cannot take any medications that are contraindicated with velpatasvir or sofosbuvir.

What is the safety track record for Sofosbuvir/Velpatasvir?

Research has shown that Sofosbuvir/Velpatasvir (SOF/VEL) is safe for use during pregnancy. Studies found that participants taking this treatment did not experience major safety issues. In some studies, all patients who completed the treatment had no detectable hepatitis C virus in their blood at the time of birth, indicating both safety and effectiveness.

Pregnant women in various studies have used this treatment successfully to clear the virus. The evidence suggests that SOF/VEL is a safe and effective option for treating hepatitis C during pregnancy. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Sofosbuvir/Velpatasvir for treating Hepatitis C in pregnancy because it offers a combination therapy that is both potent and convenient, taken as a single tablet daily. Unlike some existing treatments that may require multiple medications or injections, this oral regimen simplifies the treatment process, which is particularly beneficial during pregnancy. Additionally, Sofosbuvir/Velpatasvir is known for its high efficacy across different Hepatitis C genotypes, potentially providing a broader solution than some current options. This could mean a more universal approach to managing Hepatitis C in pregnant patients, with fewer barriers to treatment.

What is the effectiveness track record for Sofosbuvir/Velpatasvir in treating Hepatitis C during pregnancy?

Research shows that Sofosbuvir/Velpatasvir (SOF/VEL) effectively treats chronic hepatitis C. Studies have found that this treatment cures 97% to 100% of cases. In this trial, participants will receive SOF/VEL. Specifically, for pregnant women with available data, the cure rate reached 100%, as the hepatitis C virus was undetectable in their blood 12 weeks after completing the treatment. Additionally, the body's processing of the drug is similar in both pregnant and non-pregnant individuals, making SOF/VEL a promising option for treating hepatitis C during pregnancy. ^{1 2 4 5 6}

Who Is on the Research Team?

Catherine Chappell, MD, MSc

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for pregnant individuals aged 18-45 with chronic hepatitis C, between 20-30 weeks of gestation, and no major pregnancy complications. They must not have plans to relocate and should agree not to join other drug/device trials during the study. Exclusions include certain medication use, severe liver abnormalities, low blood counts, or uncontrolled health conditions.

Inclusion Criteria

I have HIV, am on antiretroviral therapy, and my latest viral load was under 50 copies/mL.

I have hepatitis C with a detectable virus level.

Singleton pregnancy at 20 + 0 to 30 + 0 weeks' gestation at enrollment with gestational dating confirmed by ultrasound

Exclusion Criteria

Any other condition that, in the opinion of the site PI/designee, would preclude appropriate informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.

I don't have any major uncontrolled health issues apart from HCV or HIV.

I was treated for hepatitis C but don't have proof of being virus-free after 12 weeks.

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 Sofosbuvir/Velpatasvir treatment for chronic hepatitis C during pregnancy

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including maternal and infant health assessments

12 weeks postpartum

3 visits (in-person)

Infant Follow-up

Infants are monitored for health and development from birth until one year of age

12 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Sofosbuvir/Velpatasvir

Trial Overview The trial tests Sofosbuvir/Velpatasvir (SOF/VEL) in treating chronic hepatitis C during pregnancy. About 100 participants will take one tablet daily for 12 weeks starting in their second or third trimester. The main goals are to see if the virus stays undetectable after treatment and how it affects delivery timing.

How Is the Trial Designed?

Group I: Sofosbuvir/Velpatasvir Experimental Treatment 1 Intervention

Sofosbuvir/Velpatasvir 400 MG-100 MG Oral Tablet, one tablet taken once daily for 84 days

Sofosbuvir/Velpatasvir is already approved in United States, European Union for the following indications:

Approved in United States as Epclusa for:

• Chronic hepatitis C genotype 1, 2, 3, 4, 5, or 6 infection (including with or without cirrhosis)

Approved in European Union as Epclusa for:

• Chronic hepatitis C genotype 1, 2, 3, 4, 5, or 6 infection (including with or without cirrhosis)

Who Is Running the Clinical Trial?

Catherine Chappell

Lead Sponsor

Trials

4

Recruited

190+

Catherine Anne Chappell

Lead Sponsor

Trials

3

Recruited

180+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

In a phase 1 study involving 9 pregnant women with hepatitis C, the combination of ledipasvir and sofosbuvir showed similar drug exposure levels compared to non-pregnant women, indicating that the treatment is pharmacokinetically safe during pregnancy.

The study found no clinically meaningful differences in the effectiveness of ledipasvir-sofosbuvir between pregnant and non-pregnant women, suggesting it can be a viable treatment option for hepatitis C in pregnant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study. Chappell, CA., Scarsi, KK., Kirby, BJ., et al.[2022]

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]

A survey of 465 clinicians in Canada revealed that while mifepristone is used by 59% of respondents for second/third-trimester medical abortion (STMA/TTMA), its use is not yet universal among providers, indicating a need for broader implementation.

The majority of clinicians providing STMA/TTMA services are general obstetrician-gynaecologists or family physicians, with many performing fewer than 5 procedures in 2019, suggesting that access to these services may be limited and that further training and resources may be necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second- and Third-Trimester Medical Abortion Providers and Services in 2019: Results From the Canadian Abortion Provider Survey. Renner, R., Ennis, M., Guilbert, E., et al.[2022]

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]

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]

The combination of sofosbuvir and velpatasvir is highly effective in treating chronic hepatitis C, achieving a sustained virologic response (SVR12) rate of 98.3% in non-cirrhotic patients and 89.7% in cirrhotic patients, based on a study of 116 patients over 12 weeks.

While the treatment is generally safe, 46.5% of participants experienced adverse events, with a higher incidence in cirrhotic patients (63.8%) compared to non-cirrhotic patients (29.3%), primarily involving gastrointestinal issues and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Sofosbuvir and Velpatasvir Combination for the Treatment of Chronic Hepatitis C in Patients With or Without Cirrhosis. Shah, I., Ahmad, W., Qadir, A., et al.[2021]

In a study involving 34 pregnant women at risk of spontaneous abortion, Partusisten treatment resulted in 27 women successfully carrying their pregnancies to term, indicating a high efficacy of the drug in preventing premature labor.

While the treatment was effective, it did cause tachycardia in mothers, but other side effects were mild and well-tolerated, suggesting that Partusisten can be a safe option for managing contractions during high-risk pregnancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tocolysis in prevention of spontaneous abortion]. Sulović, V., Avramović, D., Lazarević, B., et al.[2013]

In a study of 111 women with a history of cesarean sections, gemeprost was found to be effective for second- and third-trimester termination of pregnancy, with a median induction-to-expulsion time of about 18 hours.

The overall complication rate was relatively low at 8.1%, although there were some serious cases, including one silent uterine rupture, indicating that while effective, careful monitoring is necessary during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second- and third-trimester termination of pregnancy in women with uterine scar - a retrospective analysis of 111 gemeprost-induced terminations of pregnancy after previous cesarean delivery. Domröse, CM., Geipel, A., Berg, C., et al.[2014]

In a study of 1701 patients with hepatitis C, treatment with sofosbuvir and velpatasvir, with or without ribavirin, led to significant improvements in patient-reported outcomes (PROs), especially in those with decompensated cirrhosis, indicating effective symptom relief and quality of life enhancement during and after treatment.

Patients with decompensated cirrhosis experienced greater increases in PRO scores compared to those with compensated cirrhosis, suggesting that this treatment regimen is particularly beneficial for those with more severe liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sofosbuvir and Velpatasvir Combination Improves Patient-reported Outcomes for Patients With HCV Infection, Without or With Compensated or Decompensated Cirrhosis. Younossi, ZM., Stepanova, M., Feld, J., et al.[2022]

The study analyzed 443 women undergoing second-trimester medical abortions using mifepristone and ethacridine lactate, finding it to be safe and effective, with no cases of uterine rupture reported.

While women with prior cesarean deliveries experienced higher blood loss compared to those with normal placentation, the overall safety profile remained strong, with successful outcomes across all groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mifepristone combined with ethacridine lactate for the second-trimester pregnancy termination in women with placenta previa and/or prior cesarean deliveries. Chen, C., Lin, F., Wang, X., et al.[2022]

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]

In a study involving 622 women in Georgia, 95% successfully completed their medical abortion using 200 mg mifepristone and 400 μg buccal misoprostol, indicating high efficacy of this method.

The majority of participants (95%) reported satisfaction with the medical abortion process, and 98% preferred to take misoprostol at home, demonstrating the acceptability and feasibility of this approach outside the capital city.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability and feasibility of 400 μg buccal misoprostol after 200 mg mifepristone for early medical abortion in Georgia. Tsereteli, T., Chong, E., Louie, K., et al.[2022]

A 30-year-old pregnant woman with HIV and hepatitis C was successfully treated with a 12-week regimen of sofosbuvir and velpatasvir, leading to a cure of her hepatitis C infection.

The treatment was safe for both the mother and her newborn, who tested negative for hepatitis C at birth and remained healthy without any birth defects two years later.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful sofosbuvir lead-in monotherapy for the treatment of hepatitis C virus (HCV) infection in a pregnant woman living with HIV. Mandimika, C., Ogbuagu, O.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39688397/

Sofosbuvir/Velpatasvir Pharmacokinetics, Safety, and Efficacy ... All 10 participants who completed treatment had undetectable HCV RNA at delivery. Two participants were lost to follow-up after delivery, but 1 ...

2. askgileadmedical.com askgileadmedical.com/docs/epclusa/epclusa-use-in-pregnancy

Epclusa® (sofosbuvir/velpatasvir) Use in Pregnancy The overall SVR rate among pregnant women who had available data was 100% (8/8). Eleven of the 14 participants received SOF/VEL, including 7 who began treatment ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05140941

Sofosbuvir/​Velpatasvir Treatment of Chronic Hepatitis C ... This is a phase 4, multicenter study, single arm study of Sofosbuvir/Velpatasvir (SOF/VEL) for treatment of chronic hepatitis C infection during pregnancy.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12561008/

Pharmacokinetics of Sofosbuvir and Velpatasvir for ... In published trials, a 12-week treatment course of SOF/VEL resulted in cure rates between 97 and 100% when given as a once-a-day oral pill [7].

5. academic.oup.com academic.oup.com/cid/article-abstract/80/4/744/7924154

Sofosbuvir/Velpatasvir Pharmacokinetics, Safety, and Efficacy ... This pharmacokinetic study of sofosbuvir/velpatasvir found no clinically meaningful difference in drug exposure in pregnant versus nonpregnant people. Sofo.

6. natap.org natap.org/2024/AASLD/AASLD_14.htm

Interim results from the STORC study Safety, Tolerability, and Outcomes of SofosbuviR/Velpatasvir in Treatment of Chronic Hepatitis C Virus during Pregnancy: Interim results ...