Phase 2 Study of Yimitasvir Phosphate Capsules
A Multicenter, Randomized, Parallel Assigned, Open-label Study to Investigate the Efficacy and Safety of Yimitasvir Phosphate (DAG181)/Sofosbuvir(SOF) Combination for 12 Weeks in Subjects With Chronic Genotype 1 HCV Infection
調査の概要
詳細な説明
A phase 2, multicenter, randomized, parallel Assigned, open-label study to explore the safety, tolerability and antiviral activity of DAG181/SOF combination for 12 weeks in adult subjects with chronic genotype 1 HCV infection.
Approximately 120 HCV genotype 1 subjects without cirrhosis will be enrolled, treatment-experienced subjects are ≤20%, all subjects will be randomized (1:1) to one of the following two treatment groups by IWRS (Medidata Balance): a) DAG181 100 mg/ SOF 400 mg once daily for 12 weeks, b) DAG181 200 mg/ SOF 400 mg once daily for 12 weeks. Randomization will be stratified by "treatment-naive" or "treatment-experienced".
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
Beijing
-
Beijing、Beijing、中国、100034
- Peking University First Hospital
-
Beijing、Beijing、中国、100069
- Beijing Youan Hospital,Capital Medical University
-
Beijing、Beijing、中国、100044
- Peking University People's Hospital
-
-
Gansu
-
Lanzhou、Gansu、中国、730000
- The First Hospital of Lanzhou University
-
-
Guangdong
-
Guangzhou、Guangdong、中国、510515
- Nanfang Hospital of Southern Medical University
-
Guangzhou、Guangdong、中国、510060
- Guangzhou Eighth People's Hospital
-
-
Hainan
-
Haikou、Hainan、中国、570311
- Hainan General Hospital
-
-
Hebei
-
Shijiazhuang、Hebei、中国、050051
- The Third Hospital of Hebei Medical University
-
-
Hubei
-
Wuhan、Hubei、中国、430060
- Renmin Hospital of Wuhan University
-
Wuhan、Hubei、中国、430022
- Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
-
Wuhan、Hubei、中国、430030
- Tongji Hospital Affiliated to Tongji Medical College of Huazhong University Science & Technology
-
-
Hunan
-
Changsha、Hunan、中国、410008
- Xiangyan Hospital, Central South University
-
-
Jiangsu
-
Nanjing、Jiangsu、中国、210003
- The Second Hospital of Nanjing
-
-
Jiangxi
-
Nanchang、Jiangxi、中国、330006
- The First Affiliated Hospital of Nanchang University
-
-
Jilin
-
Chang Chun、Jilin、中国、130021
- The First Hospital of Jilin University
-
-
Shanxi
-
Xi'an、Shanxi、中国、710038
- Tangdu Hospital
-
-
Sichuan
-
Chengdu、Sichuan、中国、610041
- West China Hospital, Sichuan University
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Willing and able to provide written informed consent;
- Male or female, age≥18 years;
A female subject is eligible to enter the study if it is confirmed that she is:
- Of non-childbearing potential (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal-women > 50 years of age with cessation (for≥12 months) of previously occurring menses), or
- Of childbearing potential (Women≤50 years of age with amenorrhea will be considered to be of childbearing potential). These women must have a negative serum pregnancy test at screening, and must use specific contraceptive methods from screening until 4 weeks after last dose of study drugs, such as complete abstinence from intercourse, vaginal ring, cervical cap or contraceptive diaphragm, IUD, etc.
- All male study subjects must agree to consistently and correctly use specific contraceptive methods with their female partner from screening until 4 weeks after last dose of study drugs(except of surgical sterilization), such as complete abstinence from intercourse, condom, and their female partner use contraceptives , vaginal ring , cervical cap or contraceptive diaphragm, IUD, etc.
- Male subjects must agree to refrain from sperm donation from the date of screening until 4 weeks after the last dose of study drugs;
- Body mass index (BMI)≥18.0 and≤32.0 kg/m2, and Weight≥40 kg;
Confirmation of chronic HCV infection documented by either:
- A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or
- A liver biopsy performed prior to the Baseline/Day 1 visit with evidence of chronic HCV infection.
- Serological detection of anti-HCV antibodies was positive at screening;
- HCV RNA≥1×104 IU/mL at Screening;
- HCV genotype 1a, 1b, or mixed 1a/1b at screening as determined by the Central Laboratory;
Classification as treatment naive or treatment experienced:
- Treatment naive is defined as having never been exposed to approved or experimental HCV-specific direct-acting antiviral agents or prior treatment of HCV with interferon (with or without ribavirin);
- Treatment experienced is defined as prior treatment failure to a regimen containing interferon (IFN-α,β or Peg-IFN±RBV) that was completed at least 2 months prior to screening. and the subject's medical records must include sufficient detail of prior virologic failure to allow for categorization of prior response, as either:
i) Non-Responder: Decrease of HCV RNA<2 log at week 12 compared to baseline; ii) Partially-Responder: Decrease of HCV RNA>2 log at week 12 compared to baseline, and detectable HCV RNA levels within week 12 and week 24; iii) Breakthrough/Relapse: Subject achieved undetectable HCV RNA levels (HCV RNA < LLOQ) during treatment, but did not achieve sustained virologic response (SVR); iv) Intolerance: Subjects have discontinued interferon-based treatment due to intolerance which proved by chief complaint or medical records.
Absence of cirrhosis is defined as any one of the following:
- Liver biopsy within 2 years of Screening or at Screening showing absence of cirrhosis (e.g. Metavir score=0-3 or Ishak score<5), or
- Fibroscan within 6 months of Screening or at Screening with a result of ≤12.5 kPa.
liver biopsy results will supersede fibroscan results and be considered definitive.
- Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
Exclusion Criteria:
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
Current or prior history of any of the following:
- Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage);
- Chronic liver disease of a non-HCV etiology (Including but not limited to hemochromatosis, Wilson's disease,alfa-1 antitrypsin deficiency);
- Significant cardiac disease(Including but not limited to myocardial infarction, bradycardia) ;
- Significant pulmonary disease;
- Malabsorption syndrome or gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug;
- Central nervous system trauma, epilepsy, stroke or transient ischemic attack;
- Psychiatric illness or psychological disease or relevant medical history;
- Malignancy diagnosed before signing the informed consent form ( except for specific cancers that have been cured by surgical resection (basal cell skin cancer, etc) or cervical carcinoma in situ are allowed). subjects under evaluation for malignancy are not eligible;
- Solid organ transplantation;
- Subjects have any other medical disorder that may interfere with subjects treatment, assessment or compliance with the protocol.
Subjects has the following laboratory parameters at screening:
- ALT > 10×the upper limit of normal (ULN);
- AST > 10×ULN;
- Total bilirubin> 1.5 × ULN;
- Albumin< 3.5 g/dL;
- AFP>100 ng/mL; If 20 ng/mL≤AFP≤100 ng/mL, a liver ultrasound examination is required to exclude subjects suspected of hepatocellular carcinoma;
- INR > 1.5 x ULN;
- Hemoglobin<11 g/dL for female subjects; <12 g/dL for male subjects;
- Platelets<90 x109/L;
- Neutrophil absolute count< 1.5 ×109/L;
- HbA1c > 8.5%;
- Creatinine clearance (CLcr) <50 mL /min as calculated by the Cockcroft-Gault equation;
- HBsAg serology test results were positive;
- HIV antibody test results were positive.
- Screening ECG with clinically significant abnormalities;
- Prior exposure to approved or experimental HCV-specific direct-acting antiviral agent;
- Use of any prohibited concomitant medications;
- Significant drug allergy, or known hypersensitivity to DAG181, SOF and its metabolites, or formulation recipients;
- A positive drug screen at screening will exclude subjects unless it can be explained by non-prescription drug or prescribed medication; the diagnosis and prescription must be approved by the investigator;
- Pregnant or nursing female or male with pregnant female partner.
研究計画
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:SOF+DAG181 100 mg
Patients with genotype 1 HCV infection without cirrhosis will receive SOF+DAG181 100 mg for 12 weeks.
|
400mg錠を1日1回経口投与
他の名前:
Capsule administered orally once daily
他の名前:
|
実験的:SOF+DAG181 200 mg
Patients with genotype 1 HCV infection without cirrhosis will receive SOF+DAG181 200 mg for 12 weeks.
|
400mg錠を1日1回経口投与
他の名前:
Capsule administered orally once daily
他の名前:
|
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 subjects with sustained virologic response 12 weeks after discontinuation of therapy (SVR12)
時間枠:Posttreatment Week 12
|
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment
|
Posttreatment Week 12
|
Safety and tolerability were evaluated based on adverse event monitoring, laboratory tests, 12-lead ECG assessments, vital signs measurements and physical examinations.
時間枠:Up to posttreatment week 24
|
Up to posttreatment week 24
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Percentage of subjects with sustained virologic response 4, 8 and 24 weeks after discontinuation of therapy (SVR4,SVR8 and SVR24)
時間枠:Posttreatment Weeks 4,8 and 24
|
SVR4,SVR8 and SVR24 were defined as HCV RNA < the lower limit of quantitation (LLOQ) at 4, 8 and 24 weeks after stopping study treatment, respectively.
|
Posttreatment Weeks 4,8 and 24
|
Percentage of subjects with HCV RNA < the lower limit of quantitation (LLOQ) while on treatment
時間枠:Baseline to week 12
|
Baseline to week 12
|
|
The time to first achieve "HCV RNA < the lower limit of quantitation (LLOQ)" while on treatment
時間枠:Baseline to week 12
|
Baseline to week 12
|
|
HCV RNA change from baseline
時間枠:Up to posttreatment week 24
|
Up to posttreatment week 24
|
|
Percentage of subjects with virologic failure
時間枠:Up to posttreatment week 24
|
Virologic failure was defined as:
|
Up to posttreatment week 24
|
Viral resistance
時間枠:Up to posttreatment week 24
|
Viral resistance to DAG181 and/or SOF during treatment and after cessation of treatment
|
Up to posttreatment week 24
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- PCD-DDAG181PA-16-005
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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。
慢性HCV感染症の臨床試験
-
Ascletis Pharmaceuticals Co., Ltd.完了
-
Ain Shams University完了
-
Valme University HospitalBoehringer Ingelheimわからない
-
Johns Hopkins UniversityNational Institute of Allergy and Infectious Diseases (NIAID)募集
-
National Institutes of Health Clinical Center (CC)Bristol-Myers Squibb; National Institute of Allergy and Infectious Diseases (NIAID)完了
-
Assistance Publique - Hôpitaux de ParisGilead Sciences終了しました
-
Assistance Publique Hopitaux De Marseilleわからない
SOFの臨床試験
-
McMaster UniversityAgency for Healthcare Research and Quality (AHRQ); Grading of Recommendations Assessment, Development...完了
-
Humanity and Health Research CentreBeijing 302 Hospital; Nanfang Hospital of Southern Medical University募集
-
Humanity and Health Research CentreBeijing 302 Hospital完了
-
Gilead Sciences終了しましたC型肝炎ウイルス感染症アメリカ, イギリス, オーストラリア, ドイツ, イタリア, ニュージーランド, ベルギー, ポーランド, ロシア連邦
-
Sanjay Gandhi Postgraduate Institute of Medical...Ram Manohar Lohia Institute of Medical Sciences, Lucknow終了しました
-
Gilead Sciences完了C型肝炎ウイルス感染症アメリカ, フランス, ニュージーランド, カナダ, ドイツ, プエルトリコ, イギリス, オーストラリア, イタリア
-
Gilead Sciences完了
-
Gilead Sciences完了