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

NCT02165189 | Completed Phase 2

• 2 other identifiers: CR104281TMC435HPC2009
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 11

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.

Conditions

Hepatitits C

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Sustained Virologic Response After 12 Weeks of end of Treatment (SVR12)

  Participants will be considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (\<) 15 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the end of treatment. End of treatment is at Week 12 (for Arms 1 and 2) or Week 24 (for Arm 3); therefore, outcome will be measured at Week 24 (for Arms 1 and 2) or Week 36 (for Arm 3).

  Week 24 or Week 36

Secondary Outcomes (6)

• Percentage of Participants With Sustained Virologic Response After 4 Weeks of end of Treatment (SVR4)

  Week 16 (for Arms 1 and 2) and Week 28 (for Arm 3)

• Percentage of Participants With Undetectable Hepatitis C Virus Ribonucleic Acid (HCV-RNA)

  Weeks 2, 4, 8 and 12 (for all treatment arms) and Weeks 16 20, and 24 (for Arm 3)

• Percentage of Participants With Viral Breakthrough

  Baseline up to Week 24 (for Arms 1 and 2) and Baseline up to Week 36 (for Arm 3)

• Percentage of Participants With Viral Relapse

  Baseline up to Week 24 (for Arms 1 and 2) and Baseline up to Week 36 (for Arm 3)

• 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)

  Baseline, Week 24 (for Arms 1 and 2) and Week 36 (for Arm 3)

Study Arms (3)

Simeprevir plus Sofosbuvir plus Ribavirin (Arm 1)

EXPERIMENTAL

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.

Drug: Simeprevir; Drug: Sofosbuvir; Drug: Ribavirin

Simeprevir plus Sofosbuvir (Arm 2)

EXPERIMENTAL

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

Drug: Simeprevir; Drug: Sofosbuvir

Simeprevir plus Sofosbuvir (Arm 3)

EXPERIMENTAL

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

Drug: Simeprevir; Drug: Sofosbuvir

Interventions

Simeprevir DRUG

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

Simeprevir plus Sofosbuvir (Arm 2); Simeprevir plus Sofosbuvir plus Ribavirin (Arm 1)

Sofosbuvir DRUG

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

Simeprevir plus Sofosbuvir (Arm 2); Simeprevir plus Sofosbuvir plus Ribavirin (Arm 1)

Ribavirin 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 plus Ribavirin (Arm 1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: lead

Study Sites (11)

Unknown Facility

Aurora, Colorado, United States

Location

Unknown Facility

Gainesville, Florida, United States

Location

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Ann Arbor, Michigan, United States

Location

Unknown Facility

Detroit, Michigan, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Durham, North Carolina, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Pittsburgh, Pennsylvania, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Related Publications (1)

• 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.

  PMID: 27896858 DERIVED

Related Links

• 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.

MeSH Terms

Interventions

Simeprevir; Sofosbuvir; Ribavirin

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Study Officials

• Janssen Scientific Affairs, LLC Clinical Trial

  Janssen Scientific Affairs, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: June 17, 2014
• Study Start: August 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: November 11, 2016

Record last verified: 2016-11

Locations

US (11)