Clinical trial NCT02165189: An Efficacy and Safety Study of Simeprevir and Sofosbuvir With and Without Ribavirin in Participants With Recurrent Genotype 1 Hepatitis C Post-Orthotopic Liver Transplant
Official title: A Phase 2 Open-Label Study in Patients With Recurrent Genotype 1 Hepatitis C Post-Orthotopic Liver Transplant to Explore the Safety And Efficacy of Simeprevir and Sofosbuvir With and Without Ribavirin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitits C
Keywords: Simeprevir
Sofosbuvir
Ribavirin
Hepatitits C
Hepatitis C virus ribonucleic acid
Lead sponsor: Janssen Scientific Affairs, LLC
Sponsor class: INDUSTRY
First posted: 2014-06-17
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate sustained virologic response 12 weeks after the end of treatment (SVR12) following 12 weeks of simeprevir plus sofosbuvir with and without ribavirin (RBV) and 24 weeks of simeprevir plus sofosbuvir without RBV in post orthotopic liver transplant participants with recurrent hepatitis (inflammation of the liver) C virus (HCV) Genotype 1 infection.

Detailed description: This is a Phase 2, multicenter (when more than one hospital or medical school team work on a medical research study), partially randomized (study drug is assigned by chance), and open-label (all people know the identity of the intervention) study to explore the safety and efficacy of simeprevir plus sofosbuvir. The study will consist of a screening period (Screening and Baseline), followed by randomization. First 33 non-cirrhotic participants will be randomly assigned in a ratio of 1:1:1 into 1 of 3 treatment arms, and up to 12 cirrhotic participants will be enrolled and all will be assigned to Arm 3. All participants in treatment Arms 1 and 2 will return for treatment visits at Weeks 1, 2, 4, 8, 12, and post-treatment follow-up visits on Weeks 16 and 24. All participants in treatment Arm 3 will return for treatment visits at Weeks 1, 2, 4, 8, 12, 16, 20, and 24, and post-treatment follow-up visits on Weeks 28 and 36. Participants will receive simeprevir plus sofosbuvir and RBV for a 12-week treatment period in Arm 1, simeprevir plus sofosbuvir without RBV for a 12-week treatment period in Arm 2 and simeprevir plus sofosbuvir for a 24-week treatment period in Arm 3. Efficacy will primarily be evaluated by SVR12. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Participant must be infected with Hepatitis C virus (HCV) Genotype 1 (1a or 1b) with Baseline HCV ribonucleic acid (RNA) greater than (\>) 10,000 international unit per milliliter (IU/mL). Retesting of HCV RNA to assess eligibility will be allowed once, using an unscheduled visit during the Screening period
* Participant must have had an orthotopic liver transplant greater than or equal to (\>=) 6 months to 15 years prior to enrollment
* Participant must have had primary liver transplant
* Participant must be on a stable immunosuppressive regimen for at least 3 months prior to the Screening visit. Immunosuppression regimens may include calcineurin inhibitors (for example, tacrolimus), mammalian target of rapamycin (mTOR) inhibitor, mycophenolate mofetil, prednisone, prednisolone less than or equal to (\<=) 5 milligram per day (mg/day), other corticosteroids (except systemic dexamethasone), sirolimus, everolimus, or azathioprine. Stable immunosuppression includes normal adjustment of immunosuppressant dose but excludes changes in immunosuppressant medication and/or treatment of rejection.
* Participant's renal function as measured by the Cockcroft Gault formula must be \>30 milliliter per minute (mL/min)

Exclusion Criteria:

* Participants received prior treatment with an investigational or Food and Drug Administration (FDA) approved direct-acting antiviral drug for the treatment of hepatitis C. Prior HCV treatment with interferon or peginterferon with or without ribavirin (RBV) is allowed but must have been completed at least 3 months prior to Screening
* Participants with hepatic decompensation defined by any of the following: 1) Any post-liver transplant clinical signs including ascites, hepatic encephalopathy, and/or evidence of varices with or without variceal bleeding, and 2) Child-Turcotte-Pugh (CTP) score \>=7
* Participant has (post-transplant) any underlying serious or life-threatening condition, such as severe uncontrolled cardiopulmonary disease, vascular disease, rheumatologic condition, renal failure, dialysis, ongoing systemic infection, uncontrolled malignancy, or other serious illness that would compromise adherence to medications and ability to comply with all aspects of the study protocol
* Any other active, clinically significant disease or clinically significant findings during the Screening period of medical history, physical examination, laboratory testing, or electrocardiogram (ECG) recording that, in the investigator's opinion, would compromise the participant's safety or could interfere with the participant participating in and completing the study. Retesting of laboratory results that lead to exclusion will be allowed once using an unscheduled visit during the Screening period to assess eligibility
* Participant is a woman who is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of ribavirin (or longer when dictated by local regulations)

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response After 12 Weeks of end of Treatment (SVR12)
timeFrame: Week 24 or Week 36
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response After 4 Weeks of end of Treatment (SVR4)
timeFrame: Week 16 (for Arms 1 and 2) and Week 28 (for Arm 3)
measure: Percentage of Participants With Undetectable Hepatitis C Virus Ribonucleic Acid (HCV-RNA)
timeFrame: Weeks 2, 4, 8 and 12 (for all treatment arms) and Weeks 16 20, and 24 (for Arm 3)
measure: Percentage of Participants With Viral Breakthrough
timeFrame: Baseline up to Week 24 (for Arms 1 and 2) and Baseline up to Week 36 (for Arm 3)
measure: Percentage of Participants With Viral Relapse
timeFrame: Baseline up to Week 24 (for Arms 1 and 2) and Baseline up to Week 36 (for Arm 3)
measure: Change From Baseline in Hepatitis C Symptom and Impact Questionnaire Version 4 (HCV-SIQv4) Score at Week 24 (for Arms 1 and 2) and Week 36 (for Arm 3)
timeFrame: Baseline, Week 24 (for Arms 1 and 2) and Week 36 (for Arm 3)
measure: Change From Baseline in EuroQol 5 - Dimension (EQ-5D) Questionnaire Score at Weeks 4, 8, 12, 16, 20, 24 (for all treatment arms) and Week 36 (for Arm 3)
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24 (for all treatment arms) and Week 36 (for Arm 3)
Other outcomes:
Locations:
city: Aurora
country: United States
state: Colorado
city: Gainesville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
Study officials:
affiliation: Janssen Scientific Affairs, LLC
name: Janssen Scientific Affairs, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: O'Leary JG, Fontana RJ, Brown K, Burton JR Jr, Firpi-Morell R, Muir A, O'Brien C, Rabinovitz M, Reddy R, Ryan R, Shprecher A, Villadiego S, Prabhakar A, Brown RS Jr. Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant: the randomized GALAXY study. Transpl Int. 2017 Feb;30(2):196-208. doi: 10.1111/tri.12896. Epub 2017 Jan 20.