Hepatitis CPhase 1HIPNCT02683005
Study of Hepatitis C Treatment During Pregnancy
A Phase 1 study testing ledipasvir/sofosbuvir in people with Hepatitis C and Pregnancy, run by Catherine Chappell at 1 site in United States.
Trial summary
Sofosbuvir and ledipasvir (LDV/SOF) are new directly acting antiviral drugs for the treatment of hepatitis C (HCV) that are highly effective, orally administered, well tolerated and preclinical evaluations in animal models indicate safe administration during pregnancy. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women only
- Conditions the study is for
- Hepatitis C, Pregnancy
- What is being tested?
- ledipasvir/sofosbuvir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to 3 Feb 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age 18 through 39 years (inclusive) at Screening
- Able and willing to provide written informed consent to be screened for and take part in the study procedures
- Able and willing to provide adequate locator information
- Chronic HCV, genotype 1, 4, 5, 6 infection, defined as HCV antibody detected at least 6 months prior to Screening and detectable HCV RNA viral load at Screening
- Desired pregnancy at 23 + 0 to 24 + 6 weeks' gestation at Enrollment with gestational dating confirmed by ultrasound
- Singleton gestation with no known fetal abnormalities
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- Documented negative Hepatitis B testing for current infection (negative HBsAg 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
Who cannot join
- Participant report of any of the following at Screening or Enrollment:
- Previous treatment for Hepatitis C virus with an NS5A inhibitor or sofosbuvir
- Use of any medications contraindicated with concurrent use of ledipasvir or sofobuvir according to the most current HARVONI package insert
- Plans to relocate away from the study site area in the next 1 year and 4 months
- Current sexual partner is known to be infected with HIV or Hepatitis B virus
- History of cirrhosis documented by previous liver biopsy or liver imaging tests
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- 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 (AST) or alanine transaminase (ALT) greater than 10 times the upper limited of normal
- Hemoglobin less than 9 g/dL
- Platelet count less than 90,000 per mm3
- International normalized ratio (INR) > 1.5
- Creatinine greater than 1.4
- Medical history of cirrhosis
- Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.
Trial locations and contacts
1 site in 1 country.
United States1 site
Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Phase I Pharmacokinetic and Safety Trial of Ledipasvir/Sofosbuvir Fixed Dose Combination in Pregnant Women With Chronic Hepatitis C Virus Infection
Sofosbuvir and ledipasvir (LDV/SOF) are new directly acting antiviral drugs for the treatment of hepatitis C (HCV) that are highly effective, orally administered, well tolerated and preclinical evaluations in animal models indicate safe administration during pregnancy. This project will evaluate the safety and pharmacokinetics of antenatal LDV/SOF treatment for 12 weeks during the second and third trimester. If proven to be effective, antenatal treatment of HCV with LDV/SOF will prevent maternal HCV-related liver disease, perinatal transmission of HCV, and community transmission of HCV.
Read the detailed description
There are 3.2 million persons in the United States chronically infected with hepatitis C virus (HCV) with a 1-2.4% prevalence during pregnancy. The recent October 2014 approval of the fixed dose combination, containing the NS5B polymerase inhibitor sofosbuvir (SOF) 90 mg and the NS5A inhibitor ledipasvir (LDV) 400mg, marked a new era of IFN and ribavirin free, directly acting antiviral treatment for HCV. A 12 week treatment course of LDV/SOF resulted in a 99% cure rate when given as a once-a-day oral pill. Based on the animal model data submitted to the FDA, this drug combination was given a pregnancy category B designation, even though there is currently no experience with LDV/SOF in pregnant women.
Pregnancy is a time when women are uniquely motivated to engage in activities which are geared toward improvement of their own health and ensuring the health of their unborn child. As such, pregnant women have frequent prenatal care visits; and health care interventions, such as antiviral therapy and monitoring, can be easily integrated into the existing healthcare infrastructure of prenatal care. The benefits of HCV treatment are numerous, including prevention of severe liver disease, hepatocellular carcinoma, and liver transplantation, as well as improvements physical, emotional and social health. The most recent guidelines by the Infectious Disease Society of America recommend that all HCV-infected persons receive treatment. The antenatal period represents an ideal window of opportunity for treatment of HCV in pregnancy due to increased antenatal health care utilization and prevention of perinatal transmission of HCV to the infant.
Safe administration of drugs in pregnancy may require dose adjustment due to the pregnancy-induced physiologic alternations. Therefore, careful pharmacokinetic (PK) evaluation is a critical first step to ensure safe administration of drugs to both the mother and the developing fetus. This is a single-arm, single-center, open label Phase 1 evaluation of the PK and safety of treating HCV with a 12 week course of LDV/SOF in 15 HCV-infected pregnant women. Therapy will be initiated at approximately 24 weeks of gestation. In this study we will determine: 1) if the PK of the LDV and SOF are similar in pregnancy as compared to those in nonpregnant women, 2) if the viral response to LDV/SOF treatment in pregnancy is similar to that observed in nonpregnant women, and 3) if there are any initial maternal or neonatal safety concerns detected with antenatal LDV/SOF administration compared with HCV-infected historical controls delivered at our institution. From the findings of this study, future studies will seek to optimize the dose, gestational age timing and treatment duration of LDV/SOF during pregnancy. Antenatal HCV treatment will improve maternal health, prevent further HCV transmission in the community and perinatal HCV transmission to the child, and thus enhance the long-term health of two generations.
- Conditions
- Hepatitis C, Pregnancy
- Being tested
- ledipasvir/sofosbuvir
- Keywords
- treatment, pharmacokinetics
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ledipasvir/sofosbuvirDrug
Also called Harvoni
Hepatitis C treatment with ledipasvir and sofosbuvir will be initiated during pregnancy at approximately 24 weeks of gestation.
| Study group | Role | What they receive |
|---|---|---|
| Ledipasvir/Sofosbuvir | Experimental | Hepatitis C treatment will be initiated with ledipasvir (400 mg) and sofosbuvir (90mg) fixed dose combination, one pill, once daily for 12 weeks. Receives: Drug: ledipasvir/sofosbuvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under Curve (AUC) Time Frame: predose, 0.5 hr, 1 hr, 2, 3, 4, 5, 8, 12 hrs
Systemic exposure both LDV and SOF (SOF and inactive metabolite GS-331007) will be assessed at 3 gestational age time points: 1) Late second trimester between 25 + 0 and 26 + 5 weeks' gestation (after at least 10 days of therapy); 2) Early third trimester between 29 + 0 and 30 + 6 weeks' gestation; 3) Late third trimester between 33 + 0 and 34 + 6 weeks' gestation
Measured: 3 gestational age time points during the 12 weeks of treatment: 1) Between 25 + 0 and 26 + 5; 2) Between 29 + 0 and 30 + 6; 3) 33 + 0 and 34 + 6 weeks' gestation
Secondary outcomes (8)
Sustained viral response at 12 weeks post treatment (SVR 12)
An undetectable HCV viral load is considered an SVR 12.
Measured: -HCV RNA viral load will be assessed at 12 weeks after completion of LDV/SOF treatment
Number of Maternal Adverse Events
Adverse events, including pregnancy and delivery outcomes will be collected prospectively . -
Measured: -From enrollment to 12 weeks after treatment completion
Number of Participants With Abnormal Laboratory Values
Safety laboratories will be sent 4-6 weeks after the initiation of treatment and will include CBC, chemistries, liver function tests, creatinine kinase, lipase, and coagulation studies.
Measured: -From enrollment to 12 weeks after treatment completion
Major Malformations of the Neonate
Major malformations, defined as structural abnormalities with surgical, medical, or cosmetic importance
Measured: From birth until 1 year of life
Length
Length in centimeters will be collected at birth, 1 month, 6 months, and 12 months.
Measured: From birth until 1 year of life
Weight
Weight in kilograms will be collected at birth, 1 month, 6 months, and 12 months.
Measured: From birth until 1 year of life
Head circumference
Head circumference (centimeters) will be collected at birth, 1 month, 6 months and 12 months.
Measured: From birth until 1 year of life
Perninatal Hepatitis C Transmission
Perinatal HCV transmission assessed by presence of hepatitis C virus RNA from infant blood sampling at one month, six months and 12 months.
Measured: From birth until 1 year of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2016 (estimated)
- Study startSep 2016
- Primary completion3 Feb 2020
- Study completion3 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catherine Chappell
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences, University of Nebraska
- Responsible party
- Sponsor-investigator, Catherine Chappell, University of Pittsburgh
- Investigators
- Catherine A Chappell, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02683005
- Sponsor's protocol ID
- PRO16010091
- Acronym
- HIP
- Status last verified
- Mar 2020
- First submitted
- 25 Jan 2016
- Last updated
- 4 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Chappell CA, Scarsi KK, Kirby BJ, Suri V, Gaggar A, Bogen DL, Macio IS, Meyn LA, Bunge KE, Krans EE, Hillier SL. Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study. Lancet Microbe. 2020 Sep;1(5):e200-e208. doi: 10.1016/S2666-5247(20)30062-8. Epub 2020 Jul 27.
PubMed 32939459
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Pharmacokinetic and Safety Trial of Ledipasvir/Sofosbuvir Fixed Dose Combination in Pregnant Women With Chronic Hepatitis C Virus Infection
- ClinicalTrials.gov ID
- NCT02683005
- Acronym / sponsor ID
- HIP / PRO16010091
- Conditions
- Hepatitis C, Pregnancy
- Keywords
- treatment, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Catherine ChappellUniversity, hospital or other
- Collaborators
- Gilead Sciences, University of Nebraska
- Study start
- Sep 2016 (actual)
- Primary completion
- 3 Feb 2020 (actual)
- Study completion
- 3 Feb 2020 (actual)
- First posted
- 17 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sofosbuvir and ledipasvir (LDV/SOF) are new directly acting antiviral drugs for the treatment of hepatitis C (HCV) that are highly effective, orally administered, well tolerated and preclinical evaluations in animal models indicate safe administration during pregnancy. This project will evaluate the safety and pharmacokinetics of antenatal LDV/SOF treatment for 12 weeks during the second and third trimester. If proven to be effective, antenatal treatment of HCV with LDV/SOF will prevent maternal HCV-related liver disease, perinatal transmission of HCV, and community transmission of HCV.
Detailed description
There are 3.2 million persons in the United States chronically infected with hepatitis C virus (HCV) with a 1-2.4% prevalence during pregnancy. The recent October 2014 approval of the fixed dose combination, containing the NS5B polymerase inhibitor sofosbuvir (SOF) 90 mg and the NS5A inhibitor ledipasvir (LDV) 400mg, marked a new era of IFN and ribavirin free, directly acting antiviral treatment for HCV. A 12 week treatment course of LDV/SOF resulted in a 99% cure rate when given as a once-a-day oral pill. Based on the animal model data submitted to the FDA, this drug combination was given a pregnancy category B designation, even though there is currently no experience with LDV/SOF in pregnant women.
Pregnancy is a time when women are uniquely motivated to engage in activities which are geared toward improvement of their own health and ensuring the health of their unborn child. As such, pregnant women have frequent prenatal care visits; and health care interventions, such as antiviral therapy and monitoring, can be easily integrated into the existing healthcare infrastructure of prenatal care. The benefits of HCV treatment are numerous, including prevention of severe liver disease, hepatocellular carcinoma, and liver transplantation, as well as improvements physical, emotional and social health. The most recent guidelines by the Infectious Disease Society of America recommend that all HCV-infected persons receive treatment. The antenatal period represents an ideal window of opportunity for treatment of HCV in pregnancy due to increased antenatal health care utilization and prevention of perinatal transmission of HCV to the infant.
Safe administration of drugs in pregnancy may require dose adjustment due to the pregnancy-induced physiologic alternations. Therefore, careful pharmacokinetic (PK) evaluation is a critical first step to ensure safe administration of drugs to both the mother and the developing fetus. This is a single-arm, single-center, open label Phase 1 evaluation of the PK and safety of treating HCV with a 12 week course of LDV/SOF in 15 HCV-infected pregnant women. Therapy will be initiated at approximately 24 weeks of gestation. In this study we will determine: 1) if the PK of the LDV and SOF are similar in pregnancy as compared to those in nonpregnant women, 2) if the viral response to LDV/SOF treatment in pregnancy is similar to that observed in nonpregnant women, and 3) if there are any initial maternal or neonatal safety concerns detected with antenatal LDV/SOF administration compared with HCV-infected historical controls delivered at our institution. From the findings of this study, future studies will seek to optimize the dose, gestational age timing and treatment duration of LDV/SOF during pregnancy. Antenatal HCV treatment will improve maternal health, prevent further HCV transmission in the community and perinatal HCV transmission to the child, and thus enhance the long-term health of two generations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ledipasvir/Sofosbuvir | Experimental | Drug: ledipasvir/sofosbuvirHepatitis C treatment will be initiated with ledipasvir (400 mg) and sofosbuvir (90mg) fixed dose combination, one pill, once daily for 12 weeks. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Age 18 through 39 years (inclusive) at Screening
- Able and willing to provide written informed consent to be screened for and take part in the study procedures
- Able and willing to provide adequate locator information
- Chronic HCV, genotype 1, 4, 5, 6 infection, defined as HCV antibody detected at least 6 months prior to Screening and detectable HCV RNA viral load at Screening
- Desired pregnancy at 23 + 0 to 24 + 6 weeks' gestation at Enrollment with gestational dating confirmed by ultrasound
Key exclusion criteria (18 listed)
- Participant report of any of the following at Screening or Enrollment:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ledipasvir/sofosbuvirAlso: HarvoniHepatitis C treatment with ledipasvir and sofosbuvir will be initiated during pregnancy at approximately 24 weeks of gestation. | Drug | Ledipasvir/Sofosbuvir |
Primary outcome
Area Under Curve (AUC) Time Frame: predose, 0.5 hr, 1 hr, 2, 3, 4, 5, 8, 12 hrs
Time frame: 3 gestational age time points during the 12 weeks of treatment: 1) Between 25 + 0 and 26 + 5; 2) Between 29 + 0 and 30 + 6; 3) 33 + 0 and 34 + 6 weeks' gestation
Systemic exposure both LDV and SOF (SOF and inactive metabolite GS-331007) will be assessed at 3 gestational age time points: 1) Late second trimester between 25 + 0 and 26 + 5 weeks' gestation (after at least 10 days of therapy); 2) Early third trimester between 29 + 0 and 30 + 6 weeks' gestation; 3) Late third trimester between 33 + 0 and 34 + 6 weeks' gestation
8 secondary outcomes
Sustained viral response at 12 weeks post treatment (SVR 12)
Time frame: -HCV RNA viral load will be assessed at 12 weeks after completion of LDV/SOF treatment
Number of Maternal Adverse Events
Time frame: -From enrollment to 12 weeks after treatment completion
Number of Participants With Abnormal Laboratory Values
Time frame: -From enrollment to 12 weeks after treatment completion
Major Malformations of the Neonate
Time frame: From birth until 1 year of life
Length
Time frame: From birth until 1 year of life
Weight
Time frame: From birth until 1 year of life
Head circumference
Time frame: From birth until 1 year of life
Perninatal Hepatitis C Transmission
Time frame: From birth until 1 year of life
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Derived from this study: PubMed 32939459Chappell CA, Scarsi KK, Kirby BJ, Suri V, Gaggar A, Bogen DL, Macio IS, Meyn LA, Bunge KE, Krans EE, Hillier SL. Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study. Lancet Microbe. 2020 Sep;1(5):e200-e208. doi: 10.1016/S2666-5247(20)30062-8. Epub 2020 Jul 27.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine A Chappell, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ledipasvir/sofosbuvir in people with Hepatitis C and Pregnancy, run by Catherine Chappell at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under Curve (AUC) Time Frame: predose, 0.5 hr, 1 hr, 2, 3, 4, 5, 8, 12 hrs (time frame: 3 gestational age time points during the 12 weeks of treatment: 1) Between 25 + 0 and 26 + 5; 2) Between 29 + 0 and 30 + 6; 3) 33 + 0 and 34 + 6 weeks' gestation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02683005, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2020.