- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT02092350
Safety and Efficacy of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Participants With Chronic Hepatitis C and Chronic Kidney Disease (MK-5172-052) (C-SURFER)
2018년 8월 23일 업데이트: Merck Sharp & Dohme LLC
A Phase II/III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects With Chronic Hepatitis C Virus Infection and Chronic Kidney Disease
This study will evaluate the safety and efficacy of combination treatment with grazoprevir (MK-5172) + elbasvir (MK-8742) for cirrhotic and non-cirrhotic participants with chronic Genotype 1 (GT1) hepatitis C virus (HCV) infection and chronic kidney disease (CKD).
The primary study hypothesis is that the proportion of HCV GT1-infected CKD participants within the Immediate Treatment and Intensive Pharmacokinetics (PK) groups achieving a sustained viral response 12 weeks after the end of all study treatment (SVR12) will be >45%.
연구 개요
상태
완전한
정황
연구 유형
중재적
등록 (실제)
237
단계
- 2 단계
- 3단계
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Documented chronic (at least 6 months) HCV GT 1 infection (with no evidence of mixed genotypes or genotype that cannot be assigned a type)
- Evidence or no evidence of liver cirrhosis based on one of the following:
- Liver biopsy performed within 24 months of Day 1 (if participant is cirrhotic then there is no time restriction on biopsy)
- Fibroscan performed within 12 months of Day 1 of this study
- Fibrosure™ (Fibrotest™) plus aspartate aminotransferase to platelet Ratio Index [APRI] obtained during the screening period)
- Has HCV status that is one of the following:
- Treatment naïve
- Prior interferon or pegylated interferon with or without ribavarin failures (null responder, partial responder, or relapser)
- Intolerant to prior interferon or pegylated intereferon with or without ribavarin regimen
- Chronic kidney disease (defined as glomerular filtration rate [eGFR] <=29) non-dialysis dependent or on hemodialysis for at least 3 months, including individuals awaiting kidney transplant and those with failed kidney transplants but no longer on immunosuppressant therapy)
- Female participant of reproductive potential must agree to remain abstinent or use (or have their partner use) 2 acceptable methods of contraception from at least 2 weeks prior to Day 1 through 14 days after the last dose of study drugs, or longer if dictated by local regulations
Exclusion Criteria:
- Evidence of decompensated liver disease
- On peritoneal dialysis for management of kidney disease
- Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
- History of malignancy <=5 years prior to signing informed consent
- Clinical diagnosis of substance abuse
- Pregnant, breast-feeding, expecting to conceive or donate eggs, or donate sperm from Day 1 through 14 days after the last study dose, or longer if dictated by local regulations
- Organ transplant (including hematopoietic stem cell transplant) other than kidney, cornea, and hair
- Conditions requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
- Uncontrolled or poorly controlled hypertension
- Significant cardiovascular disorder (e.g. myocardial infarction or unstable angina) or cardiovascular procedure within 3 months prior to signing informed consent
- New or worsening signs or symptoms of congestive heart failure within 3 months of signing informed consent
- Severe active peripheral vascular disease
- Recent (within 3 months prior to signing informed consent) episode or recurrence of stroke, transient ischemic attack (TIA) or neurological disorder, including but not limited to seizures
- Evidence or history of chronic hepatitis not caused by HCV
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 더블
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Immediate Treatment
Participants receive grazoprevir 100 mg tablet, orally, once per day (QD) + elbasvir 50 mg tablet, orally, QD, for 12 weeks.
|
Grazoprevir 100 mg tablet
다른 이름들:
Elbasvir 50 mg tablet
다른 이름들:
|
|
실험적: Deferred Treatment
Participants receive placebos to both grazoprevir and elbasvir for 12 weeks, and after a 4-week break, grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks.
|
Grazoprevir 100 mg tablet
다른 이름들:
Elbasvir 50 mg tablet
다른 이름들:
Placebo tablet matched to grazoprevir
Placebo tablet matched to elbasvir
|
|
실험적: Intensive PK
Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing.
|
Grazoprevir 100 mg tablet
다른 이름들:
Elbasvir 50 mg tablet
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)
기간: Week 24 (Immediate Treatment + Intensive PK) or Week 40 (Deferred Treatment)
|
SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) lower than the limit of quantification (LLoQ) 12 weeks after completing study therapy.
HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
|
Week 24 (Immediate Treatment + Intensive PK) or Week 40 (Deferred Treatment)
|
|
Number of Participants Experiencing an Adverse Event (AE) During the Initial Treatment and 14-day Follow-up Periods
기간: Up to Week 14
|
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
|
Up to Week 14
|
|
Number of Participants Discontinuing Study Drug Due to AEs During the Initial Treatment Period
기간: Up to Week 12
|
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
|
Up to Week 12
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)
기간: Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment)
|
SVR24 was defined as HCV RNA <LLoQ 24 weeks after completing study therapy.
HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
|
Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment)
|
|
Percentage of Participants With Sustained Virologic Response 4 Weeks After Completing Study Therapy (SVR4)
기간: Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment)
|
SVR4 was defined as HCV RNA <LLoQ 4 weeks after completing study therapy.
HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
|
Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment)
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Jacobson IM, Lawitz E, Kwo PY, Hezode C, Peng CY, Howe AYM, Hwang P, Wahl J, Robertson M, Barr E, Haber BA. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology. 2017 May;152(6):1372-1382.e2. doi: 10.1053/j.gastro.2017.01.050. Epub 2017 Feb 11.
- Reau N, Robertson MN, Feng HP, Caro L, Yeh WW, Nguyen BT, Wahl J, Barr E, Hwang P, Klopfer SO. Concomitant proton pump inhibitor use does not reduce the efficacy of elbasvir/grazoprevir: A pooled analysis of 1,322 patients with hepatitis C infection. Hepatol Commun. 2017 Aug 22;1(8):757-764. doi: 10.1002/hep4.1081. eCollection 2017 Oct.
- Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, Martin P, Pol S, Londono MC, Hassanein T, Zamor PJ, Zuckerman E, Wan S, Jackson B, Nguyen BY, Robertson M, Barr E, Wahl J, Greaves W. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015 Oct 17;386(10003):1537-45. doi: 10.1016/S0140-6736(15)00349-9. Epub 2015 Oct 5. Erratum In: Lancet. 2015 Nov 7;386(10006):1824.
- Bruchfeld A, Roth D, Martin P, Nelson DR, Pol S, Londono MC, Monsour H Jr, Silva M, Hwang P, Arduino JM, Robertson M, Nguyen BY, Wahl J, Barr E, Greaves W. Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):585-594. doi: 10.1016/S2468-1253(17)30116-4. Epub 2017 May 30.
- Caro L, Wenning L, Feng HP, Guo Z, Du L, Bhagunde P, Fandozzi C, Panebianco D, Marshall WL, Butterton JR, Iwamoto M, Yeh WW. Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment. Eur J Clin Pharmacol. 2019 May;75(5):665-675. doi: 10.1007/s00228-018-2585-3. Epub 2019 Jan 25.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2014년 3월 17일
기본 완료 (실제)
2015년 3월 11일
연구 완료 (실제)
2015년 9월 2일
연구 등록 날짜
최초 제출
2014년 3월 17일
QC 기준을 충족하는 최초 제출
2014년 3월 17일
처음 게시됨 (추정)
2014년 3월 20일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2018년 9월 24일
QC 기준을 충족하는 마지막 업데이트 제출
2018년 8월 23일
마지막으로 확인됨
2018년 8월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 5172-052
- 2013-003858-25 (EudraCT 번호)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
예
IPD 계획 설명
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .