Oral Antivirals (GS-5885, Tegobuvir, and/or GS-9451) With Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection
2014년 1월 14일 업데이트: Gilead Sciences
A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy Using Combinations of Oral Antivirals (GS-5885, Tegobuvir, and/or GS-9451) With Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol GS US 256 0124)
This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy using Combinations of Oral Antivirals (GS-5885, tegobuvir, and/or GS-9451) with Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects with Chronic Genotype 1 Hepatitis C Virus (HCV) Infection.
연구 개요
상태
완전한
정황
상세 설명
In September 2011, the FDA requested that Gilead make several major changes to this study because of side effects experienced by two patients in other Gilead studies.
In 2 HCV-infected people that were given tegobuvir with another experimental medication plus interferon and ribavirin, big reductions in the number of white blood cells, red blood cells and platelets were seen. Because these cases might have been related to tegobuvir when given with interferon, ribavirin and another direct antiviral agent, tegobuvir is no longer being given to people with these other medications in this study.
As a result, the study is now open label which means both you and your study doctor will know the medication you will be receiving and Arms 1 and 3 have been discontinued from the study.
All subjects enrolled in the study as of September 2nd 2011 will receive Response Guided Therapy (RGT) with both GS-5885 and GS-9451 plus PEG and RBV.
연구 유형
중재적
등록 (실제)
163
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
-
-
Alabama
-
Dothan, Alabama, 미국, 36305
- Digestive Health Specialists of the Southeast
-
Montgomery, Alabama, 미국, 36116
- Alabama Liver and Digestive Specialists
-
-
California
-
Beverly Hills, California, 미국, 90211
- California Liver Institute
-
La Jolla, California, 미국, 92037
- Scripps Clinic
-
Sacramento, California, 미국, 95817
- University of California Davis Medical Center
-
San Diego, California, 미국, 92123
- Medical Associates Research Group
-
San Diego, California, 미국, 92154
- Kaiser Permanente
-
San Diego, California, 미국, 92015
- RESEARCH and EDUCATION, INC
-
-
Colorado
-
Aurora, Colorado, 미국, 80045
- University of Colorado Denver
-
Englewood, Colorado, 미국, 80110
- South Denver Gastroenterology
-
-
Florida
-
Bradenton, Florida, 미국, 34209
- Bach and Godofsky Infectious Diseases
-
Gainesville, Florida, 미국, 32610
- University of Florida
-
Miami, Florida, 미국, 33136
- University of Miami
-
Orlando, Florida, 미국, 32803
- Orlando Immunology Center
-
Wellington, Florida, 미국, 33414
- South Florida Center of Gastroenterology, LLC
-
-
Georgia
-
Atlanta, Georgia, 미국, 30309
- Digestive Healthcare of Georgia
-
Atlanta, Georgia, 미국, 30308
- Emory University, Infectious Disease Clinic
-
Decatur, Georgia, 미국, 30033
- Dekalb Gastroenterology
-
Marietta, Georgia, 미국, 30060
- Gastrointestinal Specialists of Georgia PC
-
-
Indiana
-
Indianapolis, Indiana, 미국, 46202
- Indiana University
-
Indianapolis, Indiana, 미국, 46237
- Indianapolis Gastroenterology Research Foundation
-
-
Kentucky
-
Bowling Green, Kentucky, 미국, 42101
- Graves Gilbert Clinic
-
-
Louisiana
-
Baton Rouge, Louisiana, 미국, 70809
- Gastroenterology Associates, LLC
-
-
Maryland
-
Baltimore, Maryland, 미국, 21229
- Digestive Disease Associates, PA
-
-
Massachusetts
-
Boston, Massachusetts, 미국, 02115
- Beth Israel Deaconess Medical Center
-
Worcester, Massachusetts, 미국, 01608
- Partners in Internal Medicine, P.C.
-
-
Michigan
-
Detroit, Michigan, 미국, 48202
- Henry Ford Health System
-
-
Mississippi
-
Jackson, Mississippi, 미국, 39202
- Gastrointestinal Associates, PA
-
Tupelo, Mississippi, 미국, 38801
- Digestive Health Specialists, PA
-
-
New Jersey
-
Hillsborough, New Jersey, 미국, 08844
- ID Care 105
-
Morristown, New Jersey, 미국, 07960
- Atlantic Research Affiliates, LLC
-
-
New Mexico
-
Santa Fe, New Mexico, 미국, 87505
- Southwest CARE Center
-
-
New York
-
Binghamton, New York, 미국, 13903
- Binghamton Gastroenterology
-
Manhasset, New York, 미국, 11030
- North Shore University Hospital
-
New York, New York, 미국, 10016
- Concorde Medical Group
-
New York, New York, 미국, 10021
- Cornell University Gastroenterology & Hepatology
-
-
North Carolina
-
Asheville, North Carolina, 미국, 28801
- Asheville Gastroenterology Associates, P.A.
-
Durham, North Carolina, 미국, 27710
- Duke University Medical Center
-
Fayetteville, North Carolina, 미국, 28304
- Cumberland Research Associates, LLC
-
-
Ohio
-
Cincinnati, Ohio, 미국, 45267
- University of Cincinnati
-
-
Oklahoma
-
Tulsa, Oklahoma, 미국, 74104
- Options Health Research, LLC
-
-
Rhode Island
-
Providence, Rhode Island, 미국, 02905
- University Gastroenterology
-
-
Tennessee
-
Germantown, Tennessee, 미국, 38138
- Memphis Gastroenterology Group
-
Nashville, Tennessee, 미국, 37205
- Nashville Medical Research Institute
-
Nashville, Tennessee, 미국, 37211
- Nashville Gastrointestinal Specialists, Inc
-
Nashville, Tennessee, 미국, 37203
- Columbia Medical Group, The Frist Clinic
-
-
Texas
-
Arlington, Texas, 미국, 76012
- The North Texas Research Institute
-
Dallas, Texas, 미국, 75246
- Baylor University Medical Center
-
Houston, Texas, 미국, 77005
- Kelsey Research Foundation
-
Houston, Texas, 미국, 77030
- Research Specialists of Texas
-
-
Virginia
-
Fairfax, Virginia, 미국, 22031
- Metropolitan Research
-
Norfolk, Virginia, 미국, 23502
- Digestive and Liver Disease Specialists
-
Richmond, Virginia, 미국, 23249
- Liver Institute of Virginia
-
-
Washington
-
Seattle, Washington, 미국, 98101
- Virginia Mason Medical Center, Digestive Disease Institute
-
-
-
-
-
San Juan, 푸에르토 리코, 00927
- Fundacion De Investigacion de Diego
-
-
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 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Male or female, aged from 18 to 70 years old, inclusive
- Chronic HCV infection for at least 6 months prior to Baseline
- Subjects must have liver biopsy results (≤ 3 years prior to screening) indicating the absence of cirrhosis.
- Monoinfection with HCV genotype 1
- HCV RNA > 10^4 IU/mL at Screening
- Prior treatment and adherence (as defined by receiving at least 80% of the prescribed treatment) with one course of a pegylated interferon-alfa (Pegasys or Peg-Intron) and RBV
The subject's medical records must include sufficient detail of prior treatment with pegylated interferon-alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either
- Non-Responder: Subject did not achieve undetectable HCV RNA levels during or at the end of a treatment period of at least 12 weeks duration. Within Nonresponders, subjects will be further defined as Null or Partial Responders if they had < 2 log10 or ≥ 2 log10 reduction, respectively, in HCV RNA during the first 12 weeks of treatment
- Responder: Subject achieved undetectable HCV RNA during treatment. Within Responders, subjects will be further defined as Relapsers if they had undetectable HCV RNA at the end of at least 42 weeks of treatment but detectable HCV RNA levels observed within 1 year of the end of treatment and Breakthrough subjects if they achieved undetectable HCV RNA levels during the treatment period but detectable HCV RNA at the end of treatment.
- No prior treatment with an oral HCV antiviral (exclusive of RBV).
- Body mass index (BMI) 18-36 kg/m2, inclusive.
- Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula) ≤ 450 msec for males and ≤ 470 msec for females
- Creatinine clearance ≥ 50 mL/min.
- Agree to use two forms of highly effective contraception for the duration of the study and for 6 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at Screening and Baseline
Exclusion Criteria:
- Discontinued prior treatment with pegylated interferon-alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up.
- Exceed defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH)
- Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), or another HCV genotype, hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
- Current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone are excluded, however stable buprenorphine maintenance treatment for at least 6 months is not exclusionary
- Receiving any of the prohibited concomitant medications.
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
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Arm 2
AM Dosing: One GS-5885 30 mg tablet, two GS-9451 100 mg tablets, orally with RBV and with food. PM Dosing: RBV with food. PEG, 180 µg, will be administered weekly by subcutaneous injection for the specified period of time (see Study Design). Pegasys® prefilled syringes (Hoffman-La Roche) will be supplied by Gilead Sciences. |
30 mg active tablet
two active 100 mg tablets
peginterferon alfa-2a (solution for injection) 180 µg/week
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Sustained Virologic Response (SVR)
기간: through 24 weeks of off-treatment follow-up
|
To evaluate antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA < Lower Limit of Quantification (LLoQ) 24 weeks post-treatment) of response guided therapy (RGT) with GS-9451 + GS-5885, with peginterferon alfa-2a (PEG) and ribavirin (RBV) in treatment-experienced subjects.
|
through 24 weeks of off-treatment follow-up
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks
기간: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment
|
To evaluate antiviral efficacy as measured by SVR for 24 or 48 weeks of treatment with GS-5885, GS-9451, PEG, RBV.
|
Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment
|
|
Safety and Tolerability
기간: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
|
To evaluate the safety and tolerability of treatment with GS-5885, GS-9451, PEG & RBV administered for 24 or 48 weeks.
Safety endpoints will be summarized as the number (proportion) of subjects with events or abnormalities for categorical values or as an 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment arm.
|
through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
|
|
Characterize the viral dynamics of GS-5885, GS-9451 when administered in combination with PEG and RBV
기간: Through Week 2 of therapy
|
HCV RNA levels, pharmacokinetics, and viral sequencing
|
Through Week 2 of therapy
|
|
Characterize the pharmacokinetics of GS-5885 and GS-9451 when administered in combination with PEG and RBV
기간: Through Week 2 of therapy
|
Plasma concentrations of the study drug over time will be summarized using descriptive statistics.
Pharmacokinetic parameters (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed and summarized for GS-5885 and GS-9451, using descriptive statistics (eg, sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and maximum).
|
Through Week 2 of therapy
|
|
Emergence of Viral Resistance
기간: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
|
To characterize the viral resistance to GS-5885 and GS 9451tegobuvir when administered in combination with PEG and RBV.
|
through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
스폰서
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
2011년 7월 1일
기본 완료 (실제)
2013년 3월 1일
연구 완료 (실제)
2013년 3월 1일
연구 등록 날짜
최초 제출
2011년 6월 9일
QC 기준을 충족하는 최초 제출
2011년 6월 10일
처음 게시됨 (추정)
2011년 6월 13일
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
2014년 2월 11일
QC 기준을 충족하는 마지막 업데이트 제출
2014년 1월 14일
마지막으로 확인됨
2014년 1월 1일
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- GS-US-256-0124
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. .