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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 (GALAXY)

2016年11月10日 更新者:Janssen Scientific Affairs, LLC

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

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.

調査の概要

詳細な説明

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.

研究の種類

介入

入学 (実際)

46

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

    • Colorado
      • Aurora、Colorado、アメリカ
    • Florida
      • Gainesville、Florida、アメリカ
      • Miami、Florida、アメリカ
    • Massachusetts
      • Boston、Massachusetts、アメリカ
    • Michigan
      • Ann Arbor、Michigan、アメリカ
      • Detroit、Michigan、アメリカ
    • New York
      • New York、New York、アメリカ
    • North Carolina
      • Durham、North Carolina、アメリカ
    • Pennsylvania
      • Philadelphia、Pennsylvania、アメリカ
      • Pittsburgh、Pennsylvania、アメリカ
    • Texas
      • Dallas、Texas、アメリカ

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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)

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

  • 主な目的:処理
  • 割り当て:ランダム化
  • 介入モデル:並列代入
  • マスキング:なし(オープンラベル)

武器と介入

参加者グループ / アーム
介入・治療
実験的: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.
Participants will be administered simeprevir capsule 150 mg orally once daily up to 12 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 12 weeks.
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.
Participants will be administered simeprevir capsule 150 mg orally once daily up to 24 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 24 weeks.
実験的: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.
Participants will be administered simeprevir capsule 150 mg orally once daily up to 12 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 12 weeks.
Participants will be administered simeprevir capsule 150 mg orally once daily up to 24 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 24 weeks.
実験的:Simeprevir plus Sofosbuvir (Arm 3)
Participants will be administered simeprevir 150 mg capsule and sofosbuvir 400 mg tablet orally once daily 24 weeks.
Participants will be administered simeprevir capsule 150 mg orally once daily up to 12 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 12 weeks.
Participants will be administered simeprevir capsule 150 mg orally once daily up to 24 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 24 weeks.

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Percentage of Participants With Sustained Virologic Response After 12 Weeks of end of Treatment (SVR12)
時間枠:Week 24 or Week 36
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

二次結果の測定

結果測定
メジャーの説明
時間枠
Percentage of Participants With Sustained Virologic Response After 4 Weeks of end of Treatment (SVR4)
時間枠:Week 16 (for Arms 1 and 2) and Week 28 (for Arm 3)
Participants will be considered to have achieved SVR4 if the hepatitis C virus ribonucleic acid (HCV RNA) is <15 IU/mL (detectable or undetectable) at 4 weeks after the end of treatment.
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)
時間枠:Weeks 2, 4, 8 and 12 (for all treatment arms) and Weeks 16 20, and 24 (for Arm 3)
Plasma HCV RNA will be determined using an in vitro nucleic acid amplification test for the quantification of HCV RNA in human plasma using a sensitive assay (COBAS® AmpliPrep/COBAS® TaqMan® HCV Test v2.0 , lower limit of quantification = limit of detection = 15 IU/mL).
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
時間枠:Baseline up to Week 24 (for Arms 1 and 2) and Baseline up to Week 36 (for Arm 3)
Viral breakthrough is defined as confirmed greater than (>) 1.0 Log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA <15 IU/mL.
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
時間枠:Baseline up to Week 24 (for Arms 1 and 2) and Baseline up to Week 36 (for Arm 3)
Participants will be considered to have viral relapse if they meet the following conditions: 1) HCV RNA <15 IU/mL (undetectable) at the end of treatment; and 2) HCV RNA greater than or equal to (>=) 15 IU/mL during the post-treatment follow-up period.
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)
時間枠:Baseline, Week 24 (for Arms 1 and 2) and Week 36 (for Arm 3)
The HCV-SIQv4 is a self-administered questionnaire containing 33 items classified as 3 categories of scores: 1) Symptom severity score (sum of responses to 29 questions to assess severity or frequency of symptoms associated with HCV or its treatment; 2) Time missed from work/school (sum of responses to 3 questions regarding the impact of symptoms on work/school attendance); 3) Daily activity score (response to 1 question regarding the impact of symptoms on daily activities). Higher HCV SIQv4 scores indicate worse symptom severity, more time missed from work/school, and more impairment in daily activities, respectively. The total score is the sum of scores of these 3 categories.
Baseline, Week 24 (for Arms 1 and 2) and Week 36 (for Arm 3)
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)
時間枠:Baseline, Weeks 4, 8, 12, 16, 20, 24 (for all treatment arms) and Week 36 (for Arm 3)
The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening. EQ-5D scores include EQ-5D valuation index score (a weighted scoring of the 5 dimension scores with a possible range from 0 to 1), EQ-5D visual analog scale (VAS) is a 20 centimeter (cm) vertical VAS with scores ranging from 0 (worst imaginable health) to 100 (perfect health), and EQ5D descriptive system scores (five scores reflecting each of the 5 EQ-5D health dimensions ranging from 0 [no limitation] to 4 [incapacity]).
Baseline, Weeks 4, 8, 12, 16, 20, 24 (for all treatment arms) and Week 36 (for Arm 3)

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2014年8月1日

一次修了 (実際)

2015年11月1日

研究の完了 (実際)

2015年11月1日

試験登録日

最初に提出

2014年6月10日

QC基準を満たした最初の提出物

2014年6月13日

最初の投稿 (見積もり)

2014年6月17日

学習記録の更新

投稿された最後の更新 (見積もり)

2016年11月11日

QC基準を満たした最後の更新が送信されました

2016年11月10日

最終確認日

2016年11月1日

詳しくは

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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