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

NCT ID: NCT02165189

Last Updated: 2016-11-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2015-11-30

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.

Conditions

Hepatitits C

Keywords

Simeprevir; Sofosbuvir; Ribavirin; Hepatitits C; Hepatitis C virus ribonucleic acid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Simeprevir plus Sofosbuvir plus Ribavirin (Arm 1)

Participants will be administered simeprevir capsule 150 milligram (mg), sofosbuvir 400 mg tablet, and ribavirin 2 x 200 mg tablets (for participants weighing less than 75 kilogram \[kg\]) or 3 x 200 mg tablets (for participants weighing more than 75 kg weight), orally once daily up to 12 weeks.

Group Type: EXPERIMENTAL

Simeprevir

Intervention Type: DRUG

Participants will be administered simeprevir capsule 150 mg orally once daily up to 12 weeks.

Sofosbuvir

Intervention Type: DRUG

Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 12 weeks.

Ribavirin

Intervention Type: DRUG

Participants will be administered ribavirin 2 x 200 mg tablets (for participants weighing less than 75 kilogram (\[kg\]) or 3 x 200 mg tablets (for participants weighing more than 75 kg) orally once daily up to 12 weeks.

Simeprevir plus Sofosbuvir (Arm 2)

Participants will be administered simeprevir capsule 150 mg and sofosbuvir 400 mg tablet orally once daily up to 12 weeks.

Group Type: EXPERIMENTAL

Simeprevir

Intervention Type: DRUG

Participants will be administered simeprevir capsule 150 mg orally once daily up to 12 weeks.

Sofosbuvir

Intervention Type: DRUG

Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 12 weeks.

Simeprevir plus Sofosbuvir (Arm 3)

Participants will be administered simeprevir 150 mg capsule and sofosbuvir 400 mg tablet orally once daily 24 weeks.

Group Type: EXPERIMENTAL

Simeprevir

Intervention Type: DRUG

Participants will be administered simeprevir capsule 150 mg orally once daily up to 24 weeks.

Sofosbuvir

Intervention Type: DRUG

Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 24 weeks.

Interventions

Simeprevir

Participants will be administered simeprevir capsule 150 mg orally once daily up to 12 weeks.

Intervention Type: DRUG

Sofosbuvir

Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 12 weeks.

Intervention Type: DRUG

Ribavirin

Participants will be administered ribavirin 2 x 200 mg tablets (for participants weighing less than 75 kilogram (\[kg\]) or 3 x 200 mg tablets (for participants weighing more than 75 kg) orally once daily up to 12 weeks.

Intervention Type: DRUG

Simeprevir

Participants will be administered simeprevir capsule 150 mg orally once daily up to 24 weeks.

Intervention Type: DRUG

Sofosbuvir

Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 24 weeks.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Scientific Affairs, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Scientific Affairs, LLC

Locations

Aurora, Colorado, United States

Gainesville, Florida, United States

Miami, Florida, United States

Boston, Massachusetts, United States

Ann Arbor, Michigan, United States

Detroit, Michigan, United States

New York, New York, United States

Durham, North Carolina, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27896858 (View on PubMed)

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_7051&studyid=7064&filename=(CR104281)_CSR%20.pdf

A Phase 2 Open-label Study in Patients With Recurrent Genotype 1 Hepatitis C Postorthotopic Liver Transplant to Explore the Safety and Efficacy of Simeprevir and Sofosbuvir With and Without Ribavirin.

Other Identifiers

TMC435HPC2009

Identifier Type: OTHER

Identifier Source: secondary_id

CR104281

Identifier Type: -

Identifier Source: org_study_id