Sofosbuvir-Containing Regimens Without Interferon For Treatment of Acute HCV in HIV-1 Infected Individuals (SWIFT-C)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 12
- 主要终点
- Percentage of Participants With Sustained Virologic Response 12 (SVR12)
研究概览
简要总结
Early identification of acute HCV infection is essential to prevent chronic infections and the long-term liver disease complications that may occur. Early identification and treatment of HCV during the acute phase can result in significantly higher response rates with shorter durations of therapy.
Pegylated-interferon alfa (PEG-IFN) was the typical treatment for HCV infection. Participants subcutaneously inject PEG-IFN where the average duration of treatment was approximately 20 weeks. With the advancement of direct-acting antivirals (DAAs), it was possible to see if a new DAA might be non-inferior compared to (PEG-IFN).
The study was designed to see if a fixed-dose combination tablet can replace the old HCV treatments by being more effective, safer and better tolerated in HIV-infected participants with new HCV infection. The study was a Phase I, open-label, two cohort clinical trial, in which 44 acutely HCV-infected HIV-1 positive participants were enrolled. Participants in each cohort were evaluated in two steps: on treatment (Step 1) and follow-up after discontinuing study treatment (Step 2). The cohorts were enrolled sequentially. Participants in Cohort 1 were enrolled and administered oral Sofosbuvir (SOF) in combination with weight-based ribavirin (RBV). Participants in Cohort 2 were enrolled and administered an oral fixed dose combination of Ledipasvir/Sofosbuvir (LDV/SOF).
详细描述
The first cohort opened with SOF/RBV treatment for 12 weeks and accrued 17 participants. All participants under Cohort 1 were to visit the clinical site at weeks 0, 1, 2, 4, 8, and 12 when on treatment (Step 1), then visit the clinical site again at 2, 4, 8, 12 and 24 weeks during follow-up after discontinuing study treatment (Step 2).
The second cohort opened for an 8-week treatment of LDV/SOF and included at least 27 subjects. All participants under Cohort 2 were to visit the clinical site at weeks 0, 1, 2, 4, and 8 when on treatment (Step 1), then visit the clinical site again at 2, 4, 8, 12 and 24 weeks during follow-up after discontinuing study treatment (Step 2).
Both cohorts were monitored for safety and HCV viral load response while the participants were on treatment.
The primary objective did not compare the cohorts together; instead, each study cohort was formally assessed for efficacy with sustained virologic response 12 weeks after treatment based on non-inferiority criteria compared to a historical SVR rate of 60% separately.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1: SOF+weight-based RBV for 12 wks
Participants in Cohort 1 were assigned Sofosbuvir (SOF)+weight-based ribavirin (RBV) for 12 weeks. Follow-up visits occurred through to 24 weeks after the end of treatment.
干预措施: Sofosbuvir (Drug)
Cohort 1: SOF+weight-based RBV for 12 wks
Participants in Cohort 1 were assigned Sofosbuvir (SOF)+weight-based ribavirin (RBV) for 12 weeks. Follow-up visits occurred through to 24 weeks after the end of treatment.
干预措施: Ribavirin (Drug)
Cohort 2: LDV/SOF for 8 wks
Participants in Cohort 2 were assigned Ledipasvir/Sofosbuvir for 8 weeks. Follow-up visits occurred through to 24 weeks after the end of treatment.
干预措施: Ledipasvir/Sofosbuvir (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Virologic Response 12 (SVR12)
时间窗: At 12 weeks after date of last dose of study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.
SVR12 was defined as HCV RNA undetectable less than the lower limit of quantification, Target Not Detected (\<LLOQ TND) of the assay at 12 weeks after date of last dose of study treatment. For both Cohort 1 and Cohort 2, the 12 week measurement used for determining SVR12 was the measurement obtained closest to 84 days (i.e. 12\*7 days), within the window 79 to 112 days inclusive. If a participant did not have an HCV RNA measurement within this window, then the participant was considered as having detectable HCV RNA at 12 weeks unless the preceding and subsequent HCV RNA measurements were both undetectable (\<LLOQ TND). A two-sided 90% confidence interval was calculated for this percentage using the Blyth-Still-Casella method.
Percentage of Participants With an Occurrence of a Grade ≥ 2 Adverse Event, Serious AE According to ICH Criteria, or Treatment-limiting AE.
时间窗: From initiation of study treatment to 28 days after last dose of study treatment. The duration for study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.
Any adverse event occurring after initiation of study treatment through to 28 days after the date of last dose of study treatment was included (except that an event that was ongoing at the same grade from before start of study treatment was excluded). Adverse events consisted of Grade ≥ 2 primary diagnosis, primary sign/symptoms, and primary laboratory abnormality. It also included any serious adverse event according to ICH criteria and any treatment-limiting AE (ie, an AE reported as the reason for permanent discontinuation of study treatment). A two-sided 90% confidence interval was calculated for the percentage using the Blyth-Still-Casella method.
次要结局
- Percentage of Participants With HCV RNA Undetectable During Study Treatment(1, 2, 4, 8 and, for the 12-week regimen, 12 weeks after starting study treatment.)
- Percentage of Participants With HCV RNA Undetectable After End of Study Treatment(2, 4, 8 and 24 weeks after last dose of study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.)
- Percentage of HCV Virologic Failure Participants That Developed SOF- or LDV-Associated Resistance Mutations(At time of HCV virologic failure; any time from start of study treatment to 24 weeks after end of study treatment. Duration of study treatment for Cohort 1 and 2 were 12 and 8 weeks, respectively.)
- Count of Participants With HIV-1 RNA <50 Copies/mL(4 and 12 weeks after start of study treatment for Cohort 1. 4 and 8 weeks after start of study treatment for the 8-week regimen used in Cohort 2))
- Adherence as Measured by RBV Pill Count(12 weeks after starting study treatment.)
- Self-reported Adherence to LDV/SOF(1, 2, 4, and 8 weeks after starting study treatment.)
- Count and Percentage of Participants With an Adverse Event by Type.(Any time from start of treatment to 28 days after date of last dose of study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.)
- Change in CD4+ Cell Count(Baseline to 12 weeks after end of study treatment. Duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.)
- Self-reported Adherence to SOF(1, 2, 4, 8 and 12 weeks after starting study treatment.)
- Adherence as Measured by SOF Pill Count(12 weeks after starting study treatment.)
- Self-reported Adherence to RBV(1, 2, 4, 8 and 12 weeks after starting study treatment.)
- Adherence as Measured by LDV/SOF Pill Count(8 weeks after starting study treatment.)
- Ribavirin Concentration in Plasma(4, 8, and 12 weeks after starting study treatment.)
- Number of Participants Who Had HCV Virologic Relapse(From end of study treatment through to 24 weeks after end of study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.)
- Cellular Concentration of Tenofovir Diphosphate (TFV-DP)(Baseline (before HCV study treatment), EOT (end of trial dosing), 12 weeks after end of HCV study treatment. The duration of HCV study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.)
- Concentration of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs)(Baseline (before SOF + RBV dosing), EOT (end of study treatment), 12 weeks after end of HCV study treatment.)
- Concentration of Tenofovir (TFV) in Plasma(Baseline (before HCV study treatment), EOT (end of trial dosing), 12 weeks after end of HCV study treatment. The duration of HCV study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.)