Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B (HBRN)
調査の概要
詳細な説明
To determine the efficacy of treatment with 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon in the treatment of chronic hepatitis B in hepatitis B "e" antigen (HBeAg) positive adults who are in the immune tolerant phase.
To evaluate safety and sustained responses after treatment with entecavir and peginterferon alfa-2a in the treatment of chronic hepatitis B in HBeAg positive adults who are in the immune tolerant phase.
A single arm treatment study of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon alfa-2a in adults with HBeAg-positive chronic hepatitis B with normal or near normal alanine aminotransferase (ALT) levels and high serum levels of hepatitis B virus (HBV) DNA ("immune tolerant" HBeAg-positive chronic hepatitis B). All participants followed for 48 weeks after treatment discontinuation (week 96 for those who completed treatment).
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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California
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Los Angeles、California、アメリカ、90095
- University of California Los Angeles
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Los Angeles、California、アメリカ、90048
- Cedars Sinai Medical Center
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San Francisco、California、アメリカ、94143
- University of California San Francisco
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San Francisco、California、アメリカ、94115
- California Pacific Medical Center
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Hawaii
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Honolulu、Hawaii、アメリカ、96813
- Queen's Medical Center
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Maryland
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Bethesda、Maryland、アメリカ、20892
- NIH Clinical Center
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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- Beth Israel Deaconess Medical Center
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
- University of Michigan Health System
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Minnesota
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Minneapolis、Minnesota、アメリカ、55446
- University of Minnesota
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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic
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Missouri
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Saint Louis、Missouri、アメリカ、63110
- Washington University
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Saint Louis、Missouri、アメリカ、63104
- Saint Louis University
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North Carolina
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Chapel Hill、North Carolina、アメリカ、27599
- University of North Carolina
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Durham、North Carolina、アメリカ、27710
- Duke University Medical Center
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Texas
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Dallas、Texas、アメリカ、75390
- University of Texas Southwestern
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Dallas、Texas、アメリカ、75246
- Baylor University Medical Center
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Virginia
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Richmond、Virginia、アメリカ、23498
- Virginia Commonwealth University
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Washington
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Seattle、Washington、アメリカ、98101
- Virginia Mason Medical Center
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Seattle、Washington、アメリカ、98105
- University of Washington Medical Center
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Ontario
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Toronto、Ontario、カナダ、M5T 2S8
- University of Toronto
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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:
- Enrolled in & completed the baseline evaluation for NCT01263587 or completed the necessary components of NCT01263587 by the end of baseline visit.
- >18 years of age at the baseline visit (day 0). Patients >50 years of age at baseline will need to have a liver biopsy as standard of care with hepatic activity index (HAI) ≤3 & Ishak fibrosis score ≤1 within 96 weeks prior to baseline visit.
- Documented chronic HBV infection as evidenced by detection of HBsAg in serum for ≥24 weeks prior to baseline visit OR at least one positive HBsAg & negative anti-hepatitis B core (HBc) immunoglobulin (IgM) within 24 weeks prior to baseline visit OR at least one positive HBsAg & two positive HBV DNA over a period of ≥24 weeks prior to baseline visit.
- Presence of HBeAg in serum at last screening visit within 6 weeks of baseline visit.
- Serum HBV DNA level >10˄7 IU/mL on at least two occasions at least 12 weeks apart during the 52 weeks before baseline visit. One of the two HBV DNA levels must be within 6 weeks of baseline visit.
- ALT levels persistently ≤45 U/L in males, ≤30 U/L in females (approx. 1.5 times the upper limit of normal (ULN) range) as documented by at least three values: one taken 28-52 weeks before baseline visit, one taken 6 to 24 weeks before the baseline visit, & the final value within 6 weeks prior to baseline visit.
- No evidence of hepatocellular carcinoma (HCC) based upon alpha-fetoprotein (AFP) ≤20 ng/mL at screening visit (up to 6 weeks prior to baseline visit). a. Participants who meet American Association for the Study of Liver Diseases (AASLD) criteria for HCC surveillance must have negative liver imaging as shown by ultrasound, computerized tomography (CT) or magnetic resonance imaging (MRI) within 28 weeks prior to baseline visit. b. Participants with AFP >20 ng/mL must be evaluated clinically with additional imaging & shown not to have HCC on CT or MRI before they can be enrolled.
Exclusion Criteria:
- History of hepatic decompensation
- Evidence of decompensated liver disease prior to or during screening, including direct bilirubin >0.5 mg/dL, international normalization ratio (INR) >1.5, or serum albumin <3.5 g/dL.
- Platelet count <120,000/mm3, hemoglobin <13 g/dL (males) or <12 g/dL (females), absolute neutrophil count < 1500 /mm3 (<1000/mm3 for African-Americans) at last screening visit.
- Previous treatment with medications that have established activity against HBV including interferon & nucleos(t)ide analogs ≥24 weeks. Patients with <24 weeks of prior HBV treatment & a wash-out period >24 weeks are not excluded.
- Known allergy or intolerance to study medications.
- Females who are pregnant or breastfeeding. Females of childbearing potential unable or unwilling to use a reliable method of contraception during the treatment period.
- Renal insufficiency with calculated creatinine clearance <50 mL/min at screening.
- History of alcohol or drug abuse within 48 weeks of baseline visit.
- Previous liver or other organ transplantation (including engrafted bone marrow).
- Any other concomitant liver disease, including hepatitis C or D. Non-alcoholic fatty liver disease (NAFLD) with steatosis &/or mild to moderate steatohepatitis is acceptable but NAFLD with severe steatohepatitis is exclusionary.
- Presence of anti-hepatitis D virus (HDV) or anti-hepatitis C virus (HCV) (unless HCV RNA negative) in serum on any occasion in the 144 weeks prior to baseline visit. Presence of anti-HIV (test completed within 6 weeks prior to baseline visit).
- Pre-existing psychiatric condition(s), including, but not limited to: current moderate or severe depression, history of depression requiring hospitalization within the past 10 years, history of suicidal or homicidal attempt within the past 10 years, history of severe psychiatric disorders as determined by a study physician.
- History of immune-mediated or cerebrovascular disease, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician.
- Any medical condition that would, in the opinion of a study physician, be predicted to be exacerbated by therapy or that would limit study participation.
- Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study.
- Evidence of active or suspected malignancy, or a history of malignancy within the 144 weeks prior to baseline visit (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).
- Expected need for ongoing use of any antivirals with activity against HBV during the course of the study.
- Concomitant use of complementary or alternative medications purported to have antiviral activity.
- Participation in any other clinical trial involving investigational drugs within 30 days of the baseline visit or intention to participate in another clinical trial involving investigational drugs during participation in this study.
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:なし
- 介入モデル:単一グループの割り当て
- 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 |
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実験的:Peginterferon and entecavir
A combination of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon.
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Entecavir 0.5 mg daily orally for 48 weeks plus peginterferon 180 µg sq weekly during weeks 9-48 of treatment.
他の名前:
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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 |
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人年当たりの重篤な有害事象(SAE)の発生率
時間枠:最初の治療から治療終了まで(最大 48 週間)およびフォローアップ終了まで(最大 96 週間)
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発生率は、SAE の数を観察の人年数で割ったものとして計算されます。これは、すべての参加者の治療開始から治療終了までの年数、またはフォロー終了までの年数の合計です。 -up、それぞれ。
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最初の治療から治療終了まで(最大 48 週間)およびフォローアップ終了まで(最大 96 週間)
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Proportion of Participants With HBeAg Loss (Lack of Detectable HBeAg) AND HBV DNA ≤1,000 IU/mL
時間枠:End of follow-up (up to 96 weeks)
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Lack of data was considered to be treatment failure.
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End of follow-up (up to 96 weeks)
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Incidence of Adverse Events (AEs) Per Person-Year of Observation
時間枠:From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
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The number of AEs includes both AEs and Serious Adverse Events (SAEs).
The incidence is calculated as the number of AEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.
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From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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HBeAg抗体陽性の参加者の割合
時間枠:治療の終了 (最大 48 週間)
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治療の終了 (最大 48 週間)
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HBeAg抗体陽性の参加者の割合
時間枠:フォローアップの終了 (最長 96 週間)
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フォローアップの終了 (最長 96 週間)
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HBsAg抗体陽性の参加者の割合
時間枠:治療の終了 (最大 48 週間)
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治療の終了 (最大 48 週間)
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HBsAg抗体陽性の参加者の割合
時間枠:フォローアップの終了 (最長 96 週間)
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フォローアップの終了 (最長 96 週間)
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HBV DNA ≤1000 IU/mL の参加者の割合
時間枠:治療の終了 (最大 48 週間)
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治療の終了 (最大 48 週間)
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HBV DNA ≤1000 IU/mL の参加者の割合
時間枠:フォローアップの終了 (最長 96 週間)
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フォローアップの終了 (最長 96 週間)
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Proportion of Participants With HBeAg Loss
時間枠:End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBeAg Loss
時間枠:End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With HBsAg Loss
時間枠:End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBsAg Loss
時間枠:End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With Alanine Aminotransferase (ALT) <45 U/L for Men, <30 U/L for Women
時間枠:End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With ALT <45 U/L for Men, <30 U/L for Women
時間枠:End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)
時間枠:End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)
時間枠:End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With HBV DNA <20 IU/mL
時間枠:End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBV DNA <20 IU/mL
時間枠:End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Absence of Detectable Antiviral Drug-resistance HBV Mutations
時間枠:End of treatment (up to 48 weeks)
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HBV drug resistance variant testing was performed at the CDC laboratory.
The sequences of the HBV polymerase spanning nucleotide positions 311-1021 were determined by Sanger sequencing.
Drug resistance mutations that were tested in this study included L80VI, L82M, T128N, W153Q, F166L, I169T, V173L, L180M, A181TV, T184ACFGILMS, V191T, A194T, A200V, S202ETV, M204IV, V207I, N236T, M250ILV, and G145R.
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End of treatment (up to 48 weeks)
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協力者と研究者
捜査官
- スタディチェア:Averell Sherker, MD、National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- 主任研究者:Anna Lok, MD、University of Michigan
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
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 (見積もり)
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
追加の関連 MeSH 用語
その他の研究ID番号
- DK082864 HBRN IT Adult Trial
- UL1RR024986 (米国 NIH グラント/契約)
- UL1TR001111 (米国 NIH グラント/契約)
- U01DK082916 (米国 NIH グラント/契約)
- U01DK082864 (米国 NIH グラント/契約)
- U01DK082874 (米国 NIH グラント/契約)
- U01DK082944 (米国 NIH グラント/契約)
- U01DK082843 (米国 NIH グラント/契約)
- U01DK082871 (米国 NIH グラント/契約)
- UL1TR000004 (米国 NIH グラント/契約)
- A-DK-3002-001 (その他の助成金/資金番号:Interagency agreement with NIDDK)
- U01DK082863 (米国 NIH グラント/契約)
- U01DK082866 (米国 NIH グラント/契約)
- U01DK082867 (米国 NIH グラント/契約)
- U01DK082872 (米国 NIH グラント/契約)
- U01DK082919 (米国 NIH グラント/契約)
- U01DK082923 (米国 NIH グラント/契約)
- U01DK082927 (米国 NIH グラント/契約)
- U01DK082943 (米国 NIH グラント/契約)
- UL1TR000058 (米国 NIH グラント/契約)
- P30DK050306 (米国 NIH グラント/契約)
- M01RR000040 (米国 NIH グラント/契約)
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?
IPD プランの説明
IPD 共有時間枠
IPD 共有アクセス基準
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
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。
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Curocell Inc.募集高悪性度B細胞リンパ腫 | びまん性大細胞型B細胞リンパ腫(DLBCL) | 原発性縦隔大細胞型B細胞リンパ腫(PMBCL) | 形質転換濾胞性リンパ腫(TFL) | 難治性大細胞型B細胞リンパ腫 | 再発大細胞型B細胞リンパ腫大韓民国
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Ohio State University Comprehensive Cancer Center募集びまん性大細胞型B細胞リンパ腫 | 高悪性度B細胞リンパ腫 | びまん性大細胞型B細胞リンパ腫、特に特定されていない | びまん性大細胞型 B 細胞リンパ腫 胚中心 B 細胞型アメリカ
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Entecavir and peginterferonの臨床試験
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Istituto per la Ricerca e l'Innovazione BiomedicaFondazione di Comunità di Messina onlus募集
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