Treatment of Chronic Hepatitis C During Pregnancy With Sofosbuvir/Velpatasvir

NCT ID: NCT04382404

Last Updated: 2025-01-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-22
• Study Completion Date: 2023-10-16

Brief Summary

A single-arm, single-center, open label Phase 1 study of a 12-week course of Sofosbuvir (SOF)/Velpatasvir (VEL) in 10 HCV-infected pregnant women 1 that will evaluate the plasma pharmacokinetic parameters of SOF/VEL administered during pregnancy and compare them to those of a historical cohort of nonpregnant women.

Detailed Description

A single-arm, single-center, open label Phase 1 study of a 12-week course of SOF/VEL in 10 HCV-infected pregnant women. Treatment will be initiated during the second trimester, reducing the risk of SOF/VEL exposure during organogenesis and ensuring treatment completion by delivery, minimizing the risk of perinatal transmission. The study will be completed in 10 or 11 visits (7 maternal visits, delivery visit and 3 infant visits) which should align with prenatal and postpartum visits. Patients will be screened between 14+0 and 22+6 weeks of gestation confirmed by ultrasound by the time of their enrollment visit who are known to have chronic HCV infection. An HCV RNA level to confirm the patient is actively infected with HCV as well as an HCV genotype will be obtained. A full laboratory evaluation of liver function will be obtained to evaluate for renal failure and decompensated cirrhosis. A Hepatitis B Virus (HBV) panel will be performed to test all patients for evidence of current or prior HBV infection before initiation of HCV treatment. If the inclusion and exclusion criteria are met, the patient will be enrolled into the study between 23+0 and 25+6 weeks' gestation and initiated on a 12 week course of SOF/VEL. Systemic exposure of both VEL and SOF (SOF and inactive metabolite GS-331007) and intracellular SOF (GS-461203) will be assessed by pharmacokinetic sampling at 3, 6, and 9 weeks after first dose. HCV RNA viral load will be assessed at 12 weeks after completion of SOF/VEL treatment. Pregnancy and delivery outcomes will be collected prospectively. Neonatal outcomes will be assessed at birth, 8 weeks, 6 months and 12 months. HCV RNA viral load will be obtained at birth (as available), 1 to 3 months, at 6 months and then again at 12 months only if negative viral loads are not documented at 1 to 3 and 6 months. Neurodevelopmental assessments will be obtained at 6 months and 12 months.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sofosbuvir-Velpatasvir

Sofosbuvir-Velpatasvir

Group Type: EXPERIMENTAL

Sofosbuvir-Velpatasvir Drug Combination

Intervention Type: DRUG

One oral pill containing 400mg sofosbuvir and 100mg velpatasvir taken once daily for 12 weeks

Interventions

Sofosbuvir-Velpatasvir Drug Combination

One oral pill containing 400mg sofosbuvir and 100mg velpatasvir taken once daily for 12 weeks

Intervention Type: DRUG

Other Intervention Names

Epclusa

Eligibility Criteria

Inclusion Criteria

• Able and willing to provide written informed consent and take part in the study -procedures
• Able and willing to provide adequate locator information
• Chronic hepatitis C viral (HCV) infection, defined as a positive HCV test at least 6 months prior to screening
• Detectable HCV RNA viral load at Screening
• Desired pregnancy at 23 + 0 to 25 + 6 weeks' gestation at enrollment with gestational dating confirmed by ultrasound
• Singleton gestation with no known fetal abnormalities
• Documented negative Hepatitis B (HB) testing for current infection (negative HB serum antigen test) or previous infection (negative anti-HB Core) performed at the screening visit
• Negative HIV testing at the screening visit
• Per participant report at screening and enrollment, agrees not to participate in other research studies involving drugs or medical devices for the duration of study participation

Exclusion Criteria

• Participant report of any of the following at screening or enrollment:

1. Previous treatment for Hepatitis C virus with sofosbuvir or a non-structural protein 5A inhibitor

2. Use of any medications contraindicated with concurrent use of velpatasvir or sofosbuvir according to the most current Epclusa package insert

3. Plans to relocate away from the study site area in the next 1 year and 4 months and unable/unwilling to return for study visits

4. Current sexual partner is known to be infected with HIV or Hepatitis B virus

5. History of cirrhosis documented or reported by previous liver biopsy or liver imaging tests

• Reports participating in any other research study involving drugs or medical devices within 60 days or less prior to enrollment
• Clinically significant and habitual non-therapeutic drug abuse, not including marijuana, as determined by Protocol Chair
• At Screening or Enrollment, as determined by the Protocol Chair, any significant uncontrolled active or chronic cardiovascular, renal, liver (such as evidence of decompensated cirrhosis by ascites, encephalopathy, or variceal hemorrhage), hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease (other than Hepatitis C)
• Has a high risk of preterm birth defined as a history of spontaneous preterm birth at less than 34 weeks of gestation or a shortened cervical length of less than 20 millimeters
• Has any of the following laboratory abnormalities at screening:

1. Aspartate aminotransferase or alanine transaminase greater than 10 times the upper limited of normal

2. Hemoglobin less than 9g/dL

3. Platelet count less than 90,000 per mm3

4. International normalized ratio > 1.5

5. Creatinine greater than 1.4

• Has any other condition that, in the opinion of the investigator or designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Catherine Anne Chappell

OTHER

Sponsor Role: lead

Responsible Party

Catherine Anne Chappell

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Catherine Chappell, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh, Magee Womens Hospital

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org; Hughes BL, Page CM, Kuller JA. Hepatitis C in pregnancy: screening, treatment, and management. Am J Obstet Gynecol. 2017 Nov;217(5):B2-B12. doi: 10.1016/j.ajog.2017.07.039. Epub 2017 Aug 4.

Reference Type: BACKGROUND

PMID: 28782502 (View on PubMed)

Gilbert EM, Darin KM, Scarsi KK, McLaughlin MM. Antiretroviral Pharmacokinetics in Pregnant Women. Pharmacotherapy. 2015 Sep;35(9):838-55. doi: 10.1002/phar.1626. Epub 2015 Aug 21.

Reference Type: BACKGROUND

PMID: 26297552 (View on PubMed)

Chappell CA, Krans EE, Bunge KE, Macio IS, Bogen D, Scarsi KK, Meyn LA, Hillier SL. A Phase 1 Study of Ledipasvir/Sofosbuvir in Pregnant Women with Hepatitis C Virus. In: Conferences on Retroviruses and Opportunistic Infections; 2010 Mar 4-7; Seattle, WA; Abstract 87

Reference Type: BACKGROUND

Ward RM, Varner MW. Principles of Pharmacokinetics in the Pregnant Woman and Fetus. Clin Perinatol. 2019 Jun;46(2):383-398. doi: 10.1016/j.clp.2019.02.014. Epub 2019 Mar 30.

Reference Type: BACKGROUND

PMID: 31010566 (View on PubMed)

MacBrayne CE, Kiser JJ. Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV. Clin Infect Dis. 2016 Jul 15;63 Suppl 1(Suppl 1):S12-23. doi: 10.1093/cid/ciw220.

Reference Type: BACKGROUND

PMID: 27363437 (View on PubMed)

Kirby BJ, Symonds WT, Kearney BP, Mathias AA. Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of the Hepatitis C Virus NS5B Polymerase Inhibitor Sofosbuvir. Clin Pharmacokinet. 2015 Jul;54(7):677-90. doi: 10.1007/s40262-015-0261-7.

Reference Type: BACKGROUND

PMID: 25822283 (View on PubMed)

Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16.

Reference Type: BACKGROUND

PMID: 26571066 (View on PubMed)

Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17.

Reference Type: BACKGROUND

PMID: 26575258 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208341s000lbl.pdf

Food and Drug Administration. Epclusa Package Insert.

Other Identifiers

R21HD101996

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY19100377

Identifier Type: -

Identifier Source: org_study_id