Treatment of Chronic Hepatitis C During Pregnancy With Sofosbuvir/Velpatasvir

NCT04382404 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: STUDY19100377R21HD101996
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C, Chronic

Keywords

pregnancy

Outcome Measures

Primary Outcomes (6)

• Maximum Concentration of Velpatasvir in Maternal Plasma

  Maximum concentration of Velpatasvir measured in maternal plasma samples. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation. At the 6-week visit, a single convenience blood sample was collected.

  Up to 9 weeks from initiation of treatment

• Maximum Concentration of Sofosbuvir in Maternal Plasma

  Maximum concentration of Sofosbuvir measured in maternal plasma samples. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation. At the 6-week visit, a single convenience blood sample was collected.

  Up to 9-weeks from initiation of treatment

• Maximum Concentration of GS-331007 in Maternal Plasma

  Maximum concentration of GS-331007, an inactive metabolite of Sofosbuvir, measured in maternal plasma samples. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation. At the 6-week visit, a single convenience blood sample was collected.

  Up to 9 weeks from initiation of treatment

• Area Under the Maternal Plasma Concentration Versus Time Curve of Velpatasvir

  Area under the maternal plasma concentration of Velpatasvir versus time curve tau of the dosing interval. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation.

  Up to 9 weeks from initiation of treatment

• Area Under the Maternal Plasma Concentration Versus Time Curve of Sofosbuvir

  Area under the maternal plasma concentration of Sofosbuvir versus time curve tau of the dosing interval. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation.

  Up to 9 weeks from initiation of treatment

• Area Under the Maternal Plasma Concentration Versus Time Curve of GS-331007

  Area under the maternal plasma concentration of GS-331007 versus time curve tau of the dosing interval; GS-331007 is an inactive metabolite of Sofosbuvir. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation.

  Up to 9 weeks from initiation of treatment

Secondary Outcomes (28)

• Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 3 Weeks

  Approximately 3 weeks from initiation of treatment

• Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 6 Weeks

  Approximately 6 weeks from initiation of treatment

• Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 9 Weeks

  Approximately 9 weeks from initiation of treatment

• Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 3 Weeks

  Approximately 3 weeks from initiation of treatment

• Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 6 Weeks

  Approximately 6 weeks from initiation of treatment

Study Arms (1)

Sofosbuvir-Velpatasvir

EXPERIMENTAL

Sofosbuvir-Velpatasvir

Drug: Sofosbuvir-Velpatasvir Drug Combination

Interventions

Sofosbuvir-Velpatasvir Drug Combination DRUG

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

Also known as: Epclusa

Sofosbuvir-Velpatasvir

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Participant report of any of the following at screening or enrollment:
• Previous treatment for Hepatitis C virus with sofosbuvir or a non-structural protein 5A inhibitor
• Use of any medications contraindicated with concurrent use of velpatasvir or sofosbuvir according to the most current Epclusa package insert
• 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
• Current sexual partner is known to be infected with HIV or Hepatitis B virus
• 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:
• Aspartate aminotransferase or alanine transaminase greater than 10 times the upper limited of normal
• Hemoglobin less than 9g/dL
• Platelet count less than 90,000 per mm3
• International normalized ratio \> 1.5

Sponsors & Collaborators

• Catherine Anne Chappell: lead
• Gilead Sciences: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Pittsburgh, Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (8)

• 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.

  PMID: 28782502 BACKGROUND

• 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.

  PMID: 26297552 BACKGROUND

• 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

  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.

  PMID: 31010566 BACKGROUND

• 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.

  PMID: 27363437 BACKGROUND

• 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.

  PMID: 25822283 BACKGROUND

• 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.

  PMID: 26571066 BACKGROUND

• 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.

  PMID: 26575258 BACKGROUND

Related Links

• Food and Drug Administration. Epclusa Package Insert.

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

sofosbuvir-velpatasvir drug combination

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Catherine Chappell
• Organization: University of Pittsburgh

chappelca@upmc.edu

412-641-1403

Study Officials

• Catherine Chappell, MD, MSc

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Open-label, single arm

Study Record Dates

• First Submitted: February 16, 2020
• First Posted: May 11, 2020
• Study Start: October 22, 2020
• Primary Completion: October 16, 2023
• Study Completion: October 16, 2023
• Last Updated: January 1, 2025
• Results First Posted: January 1, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Immediately after the primary manuscript for the study is published. Information will be available for an indefinite period of time.
• Access Criteria: Data requests submitted by email will be reviewed by the Principal Investigator on a case by case basis.

Locations

US (1)