リトナビルと組み合わせたロナファルニブの滴定用量 (LOWR-4)
デルタ型肝炎ウイルスに慢性的に感染した患者における滴定用量のロナファルニブ/リトナビルの安全性、忍容性、薬物動態、および薬力学的活性に関する第 2 相非盲検試験
A phase 2, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of titrating-dose lonafarnib/ritonavir in patients chronically infected with hepatitis delta virus (HDV)
調査の概要
詳細な説明
This is a Phase 2 study of 24 weeks of treatment with a dose-titration regimen of lonafarnib/ritonavir in up to 15 patients chronically infected with HDV: lonafarnib starting at 50 mg twice daily (BID) in combination with ritonavir 100 mg BID and escalating lonafarnib as tolerated.
The duration of the study for each patient is approximately 13 months (up to 4 weeks for screening, 24 weeks of treatment, 4 weeks for the primary follow-up visit, and monthly safety follow-up visits for 5 months thereafter). The 6-month follow-up after the last dose of study drug is designed to allow evaluation of the clinical and virologic course after completion of the 24-week Treatment Period.
研究の種類
入学 (実際)
段階
- フェーズ2
アクセスの拡大
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
Key Inclusion Criteria:
- Male or female, 18 to 65 years of age, inclusive
- Chronic HDV infection documented by a positive HDV antibody (Ab) test of at least 6 months duration and detectable HDV ribonucleic acid (RNA) by quantitative polymerase chain reaction (qPCR) at study entry
- Liver biopsy demonstrating evidence of chronic hepatitis
- Willingness to practice appropriate contraception
Key Exclusion Criteria:
-
Previous use of lonafarnib
-
Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
-
Active jaundice defined by total bilirubin level >2.0 mg/dL and known not to have Gilbert's disease
-
Decompensated liver disease or cirrhosis, history of bleeding esophageal varices, ascites, or hepatic encephalopathy
-
Serum creatinine concentration ≥1.5 times upper limit of normal (ULN)
-
Evidence of another form of viral hepatitis (not including hepatitis B virus or HCV) or another form of liver disease
-
Evidence of hepatocellular carcinoma
-
Use of alfa interferon, either interferon alfa-2a or interferon alfa-2b, or peginterferon alfa-2a within 2 months before the start of screening
-
Concomitant use of any of the following:
- Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4 or CYP2C19
- Drugs known to prolong the PR interval or QT interval of the electrocardiogram
- Receipt of systemic immunosuppressive therapy within the 3 months before start of screening
- Statins, due to inhibition of mevalonate synthesis, which reduces protein prenylation
- Medications contraindicated in the prescribing information for ritonavir
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 |
|---|---|
|
実験的：lonafarnib/ritonavir
Lonafarnib starting at 50 mg BID in combination with ritonavir 100 mg BID and escalating to lonafarnib 75 mg BID and then 100 mg BID as tolerated. The duration of the study for each patient is 6 months of treatment and 6 months follow-up. |
antiviral farnesyltransferase inhibitor
他の名前：
Cytochromes P450 3A4 inhibitor used to boost lonafarnib
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 |
|---|---|---|
|
Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer
時間枠：Baseline and Week 24 (6 months)
|
Change from baseline to Week 24 in mean HDV RNA titer following dose escalating from lonafarnib 50 mg BID to 75 mg BID and to 100 mg BID, all boosted with ritonavir 100 mg BID. |
Baseline and Week 24 (6 months)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of Patients With 1 Log Reduction From Baseline by Timepoint
時間枠：Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24
|
Number of patients with at least 1 log reduction in HDV RNA from baseline by dose level and timepoint |
Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Heiner Wedemeyer, MD, PhD、Hannover Medical School
出版物と役立つリンク
一般刊行物
- Koh C, Canini L, Dahari H, Zhao X, Uprichard SL, Haynes-Williams V, Winters MA, Subramanya G, Cooper SL, Pinto P, Wolff EF, Bishop R, Ai Thanda Han M, Cotler SJ, Kleiner DE, Keskin O, Idilman R, Yurdaydin C, Glenn JS, Heller T. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial. Lancet Infect Dis. 2015 Oct;15(10):1167-1174. doi: 10.1016/S1473-3099(15)00074-2. Epub 2015 Jul 16.
- Yurdaydin C, Keskin O, Kalkan C, Karakaya F, Caliskan A, Karatayli E, Karatayli S, Bozdayi AM, Koh C, Heller T, Idilman R, Glenn JS. Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study. Hepatology. 2018 Apr;67(4):1224-1236. doi: 10.1002/hep.29658. Epub 2018 Feb 19.
- Yurdaydin C, Keskin O, Yurdcu E, Caliskan A, Onem S, Karakaya F, Kalkan C, Karatayli E, Karatayli S, Choong I, Apelian D, Koh C, Heller T, Idilman R, Bozdayi AM, Glenn JS. A phase 2 dose-finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis. Hepatology. 2022 Jun;75(6):1551-1565. doi: 10.1002/hep.32259. Epub 2021 Dec 23.
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 (推定)
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
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