Treatment of Chronic Hepatitis C During Pregnancy With Sofosbuvir/Velpatasvir
Primary Purpose
Hepatitis C, Chronic
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sofosbuvir-Velpatasvir Drug Combination
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring pregnancy
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:
- 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
- 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
Sites / Locations
- University of Pittsburgh, Magee Womens Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sofosbuvir-Velpatasvir
Arm Description
Sofosbuvir-Velpatasvir
Outcomes
Primary Outcome Measures
Maximum Concentration of Velpatasvir in Plasma
Maximum concentration of Velpatasvir measured in plasma samples
Maximum Concentration of Sofosbuvir in Plasma
Maximum concentration of Sofosbuvir measured in plasma samples
Maximum Concentration of GS-331007 in Plasma
Maximum concentration of GS-331007, an inactive metabolite of Sofosbuvir, measured in plasma samples
Area Under the Plasma Concentration Versus Time Curve of Velpatasvir
Area under the plasma concentration versus time curve of Velpatasvir
Area Under the Plasma Concentration Versus Time Curve of Sofosbuvir
Area under the plasma concentration versus time curve of Sofosbuvir
Area Under the Plasma Concentration Versus Time Curve of GS-331007
Area under the plasma concentration versus time curve of GS-331007, an inactive metabolite of Sofosbuvir
Secondary Outcome Measures
Intracellular Concentration of GS-461203 from Peripheral Blood Mononuclear Cells
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from peripheral blood mononuclear cells
Intracellular Concentration of GS-461203 from Dried Blood Spots
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from dried blood spots
Percentage of Unbound Velpatasvir measured in Plasma
Percentage of unbound Velpatasvir out of total Velpatasvir, unbound and protein-bound, measured in plasma
Percentage of Unbound Sofosbuvir measured in Plasma
Percentage of unbound Sofosbuvir out of total Sofosbuvir, unbound and protein-bound, measured in plasma
Quantity of Hepatitis C Virus in Plasma After Completion of Velpatasvir and Sofosbuvir Treatment
Quantity of Hepatitis C RNA measured in plasma measured after completion of Velpatasvir and Sofosbuvir treatment regimen
Number of Participants That Experience Adverse Events Related to Sofosbuvir/Velpatasvir
Number of maternal and infant participants that experience an adverse event that is deemed related to Sofosbuvir/Velpatasvir by a study physician
Gestational Age at Delivery
Gestational age at delivery determined by medical record review
Infant Weight at Delivery
Infant birth weight determined by medical record review
Frequency of Delivery Modes
Frequency of delivery modes (spontaneous vaginal, assisted vaginal, cesarean section) determined by medical record review
Number of Infant Participants with Congenital Anomalies
Number of infant participants with congenital anomalies determined by medical record review
-Weight of Infant Participant
Weight of infant participant measured at 1-3 months, 6 months, and 12 months
Length of Infant Participant
Length of infant participant measured at 1-3 months, 6 months, and 12 months
Head Circumference of Infant Participant
Head circumference of infant participant measured at 1-3 months, 6 months, and 12 months
Quantity of Hepatitis C Virus in Infant Plasma
-Quantity of Hepatitis C viral RNA measured in infant plasma will be assessed at birth, 1-3 months, 6 months, and 12 months
Number of Infant Participants Referred for Early Neurological Development Intervention
Number of infant participants referred for early intervention based on neurological development assessments (Bayley's scores)
Number of Infant Participants with Any Neurological Development Score Less than 6
Number of infant participants with a Bayley's score of less than 6 on either cognitive, motor or language development assessments; Bayley's score ranges from 1 (extremely low) to 19 (very superior)
Full Information
NCT ID
NCT04382404
First Posted
February 16, 2020
Last Updated
January 6, 2023
Sponsor
Catherine Anne Chappell
Collaborators
Gilead Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT04382404
Brief Title
Treatment of Chronic Hepatitis C During Pregnancy With Sofosbuvir/Velpatasvir
Official Title
Phase 1 Pharmacokinetic Trial of Sofosbuvir/Velpatasvir in Pregnant Women With Chronic Hepatitis C Virus Infection
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 22, 2020 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Catherine Anne Chappell
Collaborators
Gilead Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
Keywords
pregnancy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Open-label, single arm
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sofosbuvir-Velpatasvir
Arm Type
Experimental
Arm Description
Sofosbuvir-Velpatasvir
Intervention Type
Drug
Intervention Name(s)
Sofosbuvir-Velpatasvir Drug Combination
Other Intervention Name(s)
Epclusa
Intervention Description
One pill once a day for 12 weeks
Primary Outcome Measure Information:
Title
Maximum Concentration of Velpatasvir in Plasma
Description
Maximum concentration of Velpatasvir measured in plasma samples
Time Frame
Approximately 3 months
Title
Maximum Concentration of Sofosbuvir in Plasma
Description
Maximum concentration of Sofosbuvir measured in plasma samples
Time Frame
Approximately 3 months
Title
Maximum Concentration of GS-331007 in Plasma
Description
Maximum concentration of GS-331007, an inactive metabolite of Sofosbuvir, measured in plasma samples
Time Frame
Approximately 3 months
Title
Area Under the Plasma Concentration Versus Time Curve of Velpatasvir
Description
Area under the plasma concentration versus time curve of Velpatasvir
Time Frame
Approximately 3 months
Title
Area Under the Plasma Concentration Versus Time Curve of Sofosbuvir
Description
Area under the plasma concentration versus time curve of Sofosbuvir
Time Frame
Approximately 3 months
Title
Area Under the Plasma Concentration Versus Time Curve of GS-331007
Description
Area under the plasma concentration versus time curve of GS-331007, an inactive metabolite of Sofosbuvir
Time Frame
Approximately 3 months
Secondary Outcome Measure Information:
Title
Intracellular Concentration of GS-461203 from Peripheral Blood Mononuclear Cells
Description
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from peripheral blood mononuclear cells
Time Frame
Approximately 3 months
Title
Intracellular Concentration of GS-461203 from Dried Blood Spots
Description
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from dried blood spots
Time Frame
Approximately 3 months
Title
Percentage of Unbound Velpatasvir measured in Plasma
Description
Percentage of unbound Velpatasvir out of total Velpatasvir, unbound and protein-bound, measured in plasma
Time Frame
Approximately 3 months
Title
Percentage of Unbound Sofosbuvir measured in Plasma
Description
Percentage of unbound Sofosbuvir out of total Sofosbuvir, unbound and protein-bound, measured in plasma
Time Frame
Approximately 3 months
Title
Quantity of Hepatitis C Virus in Plasma After Completion of Velpatasvir and Sofosbuvir Treatment
Description
Quantity of Hepatitis C RNA measured in plasma measured after completion of Velpatasvir and Sofosbuvir treatment regimen
Time Frame
Approximately 6 months
Title
Number of Participants That Experience Adverse Events Related to Sofosbuvir/Velpatasvir
Description
Number of maternal and infant participants that experience an adverse event that is deemed related to Sofosbuvir/Velpatasvir by a study physician
Time Frame
Approximately 6 months
Title
Gestational Age at Delivery
Description
Gestational age at delivery determined by medical record review
Time Frame
Approximately 6 months
Title
Infant Weight at Delivery
Description
Infant birth weight determined by medical record review
Time Frame
Approximately 6 months
Title
Frequency of Delivery Modes
Description
Frequency of delivery modes (spontaneous vaginal, assisted vaginal, cesarean section) determined by medical record review
Time Frame
Approximately 6 months
Title
Number of Infant Participants with Congenital Anomalies
Description
Number of infant participants with congenital anomalies determined by medical record review
Time Frame
Approximately 6 months
Title
-Weight of Infant Participant
Description
Weight of infant participant measured at 1-3 months, 6 months, and 12 months
Time Frame
Approximately 12 months
Title
Length of Infant Participant
Description
Length of infant participant measured at 1-3 months, 6 months, and 12 months
Time Frame
Approximately 12 months
Title
Head Circumference of Infant Participant
Description
Head circumference of infant participant measured at 1-3 months, 6 months, and 12 months
Time Frame
Approximately 12 months
Title
Quantity of Hepatitis C Virus in Infant Plasma
Description
-Quantity of Hepatitis C viral RNA measured in infant plasma will be assessed at birth, 1-3 months, 6 months, and 12 months
Time Frame
Approximately 12 months
Title
Number of Infant Participants Referred for Early Neurological Development Intervention
Description
Number of infant participants referred for early intervention based on neurological development assessments (Bayley's scores)
Time Frame
Approximately 12 months
Title
Number of Infant Participants with Any Neurological Development Score Less than 6
Description
Number of infant participants with a Bayley's score of less than 6 on either cognitive, motor or language development assessments; Bayley's score ranges from 1 (extremely low) to 19 (very superior)
Time Frame
Approximately 12 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
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:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine Chappell, MD, MSc
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh, Magee Womens Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data requests can be submitted by email to the Principal Investigator
IPD Sharing Time Frame
Immediately after the primary manuscript for the study is published. Information will be available for an indefinite period of time.
IPD Sharing Access Criteria
Data requests submitted by email will be reviewed by the Principal Investigator on a case by case basis.
Citations:
PubMed Identifier
28782502
Citation
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.
Results Reference
background
PubMed Identifier
26297552
Citation
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.
Results Reference
background
Citation
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
Results Reference
background
PubMed Identifier
31010566
Citation
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.
Results Reference
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PubMed Identifier
27363437
Citation
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. Erratum In: Clin Infect Dis. 2016 Sep 1;63(5):715.
Results Reference
background
PubMed Identifier
25822283
Citation
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.
Results Reference
background
PubMed Identifier
26571066
Citation
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.
Results Reference
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PubMed Identifier
26575258
Citation
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.
Results Reference
background
Links:
URL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208341s000lbl.pdf
Description
Food and Drug Administration. Epclusa Package Insert.
Learn more about this trial
Treatment of Chronic Hepatitis C During Pregnancy With Sofosbuvir/Velpatasvir
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