EASL2020[LBP13] Peginterferon Lambda，Lonafarnib和 利托那韋治療24週：L

StephenW

LBP13
A Phase 2 Study of Peginterferon Lambda, Lonafarnib and
Ritonavir for 24 Weeks: End-of-Treatment Results from the LIFT
HDV Study
Christopher Koh1, Julian Hercun1, Farial Rahman1, Amy Huang1,
Ben Da1, Pallavi Surana1, Devika Kapuria1, Yaron Rotman1,
Anusha Vittal1, Christy Ann Gilman1, Gil Ben Yakov1, Walter Lai1,
Harel Dahari2, Jeffrey Glenn3, Theo Heller1. 1NIDDK/NIH, Bethesda,
United States; 2Loyola University, Chicago, United States; 3Stanford
University School of Medicine, Stanford, United States
Email: [email protected].
Background and aims: Hepatitis Delta Virus (HDV) infection, the
most aggressive form of human chronic viral hepatitis, is still without
an approved FDA therapy. Clinical trials have demonstrated anti-HDV
activity with the prenylation inhibitor lonafarnib (LNF) boosted with
ritonavir (RTV) and peginterferon lambda-1a (LMD) monotherapy. In
a first-in-humans clinical trial, the Lambda InterFeron combination
Therapy (LIFT) study evaluated the safety and antiviral effects of
combination therapy with LMD/LNF/RTV in patients with chronic
HDV infection.
Method: In this phase 2a open-label study, 26 adult patients with
chronic HDV and quantifiable HDV RNA in serum (lower limit of
quantitation <40 IU/mL) have completed treatment with subcutaneous
LMD 180 mcg weekly and oral LNF 50 mg and RTV 100 mg twice
daily for 24 weeks and are undergoing per-protocol post-therapy
monitoring for 24 weeks. Tenofovir or Entecavir was started prior to
therapy. Serial assessments of safety parameters, liver tests, pharmacokinetics,
histology, and virologic (HDV RNA and HBV DNA) markers
were obtained.
Results: In this ongoing study, patients were 62% male, median age of
40 years and included Asian (54%), White (31%) and African (15%)
subjects. Median baseline evaluations included: ALT (62 IU/mL), AST
(47 IU/mL), Ishak Fibrosis (3), modified HAI inflammation (9), HBV
DNA (<21 IU/mL) and log HDV RNA (4.7 IU/mL). After 12 weeks of
therapy, the median HDV RNA decline from baseline was 3.4 log IU/mL (IQR: 2.9–3.8, p < 0.0001) with 7 patients (27%) achieving
undetectable HDV RNA and 6 patients (23%) with HDV RNA below
the lower limit of quantification (BLOQ). At the end of therapy, the
median HDV RNA declinewas 3.4 log IU/mL (IQR: 2.9–4.5, p < 0.0001)
with 11 patients (42%) achieving undetectable HDV RNA and 3
patients (11%) BLOQ. 25 of 26 patients (96%) achieved >2 log decline
during 24 weeks of therapy. Adverse events were mostly mild to
moderate and included GI related side effects, weight loss, hyperbilirubinemia,
and anemia. Therapywas dose reduced in 3 patients and
discontinued in 4 patients.
Conclusion: Triple combination therapy with LMD/LNF/RTV in
chronic HDV patients appears to be safe and tolerable for up to 6
months in most patients. After 24 weeks, almost all achieve >2 log
decline in HDV RNA during therapy with >50% achieving undetectable
or BLOQHDV RNA levels. These end-of-treatment results support
continued exploration of this therapeutic combination in HDV.

StephenW

LBP13
Peginterferon Lambda，Lonafarnib和
利托那韋治療24週：LIFT治療結束的結果
HDV研究
Christopher Koh1，Julian Hercun1，Farial Rahman1，Amy Huang1，
Ben Da1，Pallavi Surana1，Devika Kapuria1，Yaron Rotman1，
Anusha Vittal1，Christy Ann Gilman1，Gil Ben Yakov1，Walter Lai1，
Harel Dahari2，Jeffrey Glenn3，Theo Heller1。 1NIDDK / NIH，貝塞斯達，
美國; 2Loyola大學，美國芝加哥； 3斯坦福大學
美國斯坦福大學醫學院
電子郵件：[email protected]。
背景與目的：肝炎三角洲病毒（HDV）感染，
人類慢性病毒性肝炎最激進的形式，仍然沒有
批准的FDA治療。臨床試驗證明抗HDV
異戊二烯化抑製劑lonafarnib（LNF）增強了
利托那韋（RTV）和聚乙二醇干擾素lambda-1a（LMD）單藥治療。在
Lambda InterFeron組合在人類中首次臨床試驗
治療（LIFT）研究評估了安全性和抗病毒作用
LMD / LNF / RTV聯合治療慢性病患者
HDV感染。
方法：在這個2a期開放標籤研究中，有26名成人患者
血清中的慢性HDV和可量化的HDV RNA（
定量<40 IU / mL）已完成皮下治療
每週LMD 180 mcg，兩次口服LNF 50 mg和RTV 100 mg
每天24週，並且正在接受按方案治療
監測24週。替諾福韋或恩替卡韋在
治療。安全參數，肝試驗，藥代動力學的系列評估，
組織學和病毒學（HDV RNA和HBV DNA）標記
獲得了。
結果：在這項正在進行的研究中，患者為62％的男性，中位年齡為
40年，包括亞洲人（54％），白人（31％）和非洲人（15％）
科目。中位數基線評估包括：ALT（62 IU / mL），AST
（47 IU / mL），Ishak纖維化（3），改良型HAI炎症（9），HBV
DNA（<21 IU / mL）和log HDV RNA（4.7 IU / mL）。經過12週的
治療後，HDV RNA相對於基線的中位數下降為3.4 log IU / mL（IQR：2.9–3.8，p <0.0001），其中7例（27％）達到
無法檢測到HDV RNA和6例（23％）HDV RNA低於
定量下限（BLOQ）。在治療結束時，
HDV RNA中位數下降為3.4 log IU / mL（IQR：2.9–4.5，p <0.0001）
有11名患者（42％）達到了無法檢測到的HDV RNA，還有3名
患者（11％）BLOQ。 26位患者中的25位（96％）的對數下降> 2
在治療的24週內。不良事件多為輕度至
中度和包括胃腸道相關的副作用，體重減輕，高膽紅素血症，
和貧血。 3例患者的治療劑量減少了，
4例患者停藥。
結論：LMD / LNF / RTV的三聯治療
慢性HDV患者似乎安全且可耐受6
大多數患者需要幾個月的時間。 24週後，幾乎所有記錄均> 2 log
> 50％的治療期間HDV RNA下降達到無法檢測的水平
或BLOQHDV RNA水平。這些治療結束的結果支持
繼續探索HDV中的這種治療組合。