10119473 -VIROMARKERS HDV Biomarkers Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 220
- 试验地点
- 2
- 主要终点
- HDV Viral Load
研究概览
简要总结
This is an observational study, in which clinical data, samples, and any other procedures possibly already performed on participants, were performed within the scope of clinical practice or within the scope of otherwise authorized projects, and that therefore there are no procedures performed specifically for this study, which instead uses data collected previously or prospectively during an extended follow-up, but in any case within the scope of current clinical practice. Most participants have been enrolled and followed up at the project partners' clinical sites over 2023-2025. Their follow-up and sample collection will continue over the duration of the project. At the time of enrollment, demographics, medical history, medications and treatments prescribed were recorded and will be used in this study if the participant consent to be included also in VIROMARKERS. HDV genotypes/subgenotypes will be determined ex-novo on existing baseline stored samples.
The harmonization of HDV-RNA assays by utilizing standardized and validated flowcharts still represents a relevant diagnostic unmet clinical need for the appropriate monitoring of patients with CHD receiving BLV treatment. Furthermore, information on long-term virological response and factors predictive of virological outcome is scarce.
Specific primary objectives to characterise the response to bulevirtide in CHD include:
- To estimate the percentage of participants who will achieve virological response (defined as a decline in serum HDV RNA of >2 log or to undetectable HDV-RNA) and the proportion achieving undetectable HDV-RNA at week 48, 96 and 144 weeks of BLV treatment.
- To estimate the percentage of participants who will achieve biochemical response and combined response (defined as achievement of virological response and ALT normalization) at week 48, 96 and 144 weeks of BLV treatment.
- To evaluate whether HDV-RNA levels at baseline or their kinetics during the first 12 weeks of BLV treatment can predict the achievement of undetectable serum HDV-RNA during BLV treatment.
详细描述
For each participant, a blood sample was obtained at baseline and every 3 months during BLV treatment up to week 96. For a subset of participants, blood samples collected up to 144 weeks of treatment will be also available for analysis. At each time point, serum HDV-RNA was quantified with the reference RoboGene 2.0 assay used in clinical studies aimed at evaluating the efficacy of BLV.
For a subset of 80 participants followed-up at the Infectious Disease and Hepatology Unit of the University of Rome Tor Vergata and at the Policlinico of Milano, HDV RNA quantification using Altona (AltoStar assays), Qiagen and RoboGene 2.0 will be performed retrospectively in samples stored in 2023-2025 as well as in newly collected samples in 2025-2028. This will allow a comparison of the diagnostic performances of these assays and their capability to predict the achievement of virological response or undetectable HDV-RNA at week 48 and 96 and at week 144 in a subset. As such for the association analysis it will be conducted separate analyses according to the method of quantification used. Particular attention will be dedicated at comparing the sensitivity of the above-mentioned assays by evaluating their ability to detect residual HDV viremia during treatment.
Also, on this subset of approximately 80 individuals, the levels of the three different isoforms of HBsAg (L-, M- and S-HBs) will be quantified by using three different ad-hoc designed ELISA assays at the following time points: baseline, 48, and 96 weeks and 144 weeks for selected patients. These assays have been demonstrated to have high sensitivity (detection limit for each protein is 0.1 ng/ml) and a high specificity, taking advantage of a sandwich system based on anti-PreS1, anti-PreS2 and anti-S antibodies, respectively. For each patient and for each time point, total HBsAg, L-HBs, M-HBs and S-HBs levels will be quantified in duplicate.
In the analysis, the virological status of each participant enrolled will be assessed every 3 months according to the guidelines promoted by European Association for the Study of the Liver and up to 144 weeks.
The use of stored clinical specimens within this protocol will be reviewed by the Protocol Team, the VIROMARKERS Scientific Steering Committee, and EC Horizon Europe.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be > 18 years of age
- •Sign an informed consent
- •Have a diagnosis of HDV infection with or without compensated cirrhosis
- •Having started BLV monotherapy 2mg/day according to the criteria reported in the recent clinical practice guidelines on HDV infection promoted by EASL (EASL CPG 2023)
- •Be under effective treatment with nucleoside analogues with HBV-DNA <20 IU/ml at the time of starting BLV
排除标准
- •Decompensated liver disease
- •BLV combined with pegIFN
- •Past treatment with BLV
结局指标
主要结局
HDV Viral Load
时间窗: 48, 96, 144 weeks after starting Bulevirtide
HDV-RNA decline \> 2 log OR reaching undetectable HDV-RNA
次要结局
未报告次要终点
研究者
Valentina Svicher
Professor
University of Rome Tor Vergata