A Phase 1, Single-blind, Dose-escalation Study to Assess the Safety and Tolerability of Brentuximab Vedotin (ADCETRIS®) in Subjects With Human Immunodeficiency Virus (HIV)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Seagen Inc.
- 试验地点
- 2
- 主要终点
- Number of participants with laboratory abnormalities
研究概览
简要总结
This study will test brentuximab vedotin to see if it is safe for people with human immunodeficiency virus (HIV) who have low CD4+ and have received antiretroviral therapy (ART) treatment. It will also see if brentuximab vedotin raises CD4+ counts. It will study the side effects of this drug as well. A side effect is anything a drug does to the body besides treating the disease.
In this study participants will be assigned randomly to a group. Participants will get either brentuximab vedotin or placebo. A placebo looks like the drug but does not contain any medicine in it. All participants will keep getting ART during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
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
- •HIV-1 seropositive with documentation of infection
- •Immunological nonresponder, defined as:
- •Has been on ART with an HIV viral load <50 copies/mL for at least 24 months
- •Has a CD4+ T-cell lymphocyte count between 51 to 200 cells/µL
- •Life expectancy of >9 months.
- •Participant is negative for hepatitis B, or if infected with hepatitis B, receiving anti-hepatitis B therapy
- •Participants with a history of hepatitis C virus (HCV) are eligible if they have completed therapy for HCV and show sustained virologic remission (12 weeks or more)
排除标准
- •Any currently active AIDS-defining illness per Category C conditions according to the CDC Classification System for HIV Infection, with the following exceptions:
- •Limited cutaneous Kaposi's sarcoma not currently requiring systemic therapy
- •Wasting syndrome due to HIV or any other AIDS-defining illness for which no therapeutic treatment is required OR the required treatment is not included in the list of prohibited medications
- •Acute liver disease or any other active infection secondary to HIV requiring acute therapy
- •History of progressive multifocal leukoencephalopathy (PML)
- •Prior clinical John Cunningham virus (JCV) infection, history of JCV identified in cerebrospinal fluid, or presence of JCV antibodies at screening
- •Cirrhosis secondary to any cause
- •Any immunomodulating therapy (excluding premedication steroid) within 4 weeks prior to the screening visit
- •Prior malignancy within 2 years other than cutaneous basal cell or squamous cell carcinoma, carcinoma in situ of the cervix, anal intraepithelial neoplasia, or cutaneous Kaposi's sarcoma
研究组 & 干预措施
Brentuximab vedotin + ART
Brentuximab vedotin given on Day 1 and Day 15. ART will be given throughout the study.
干预措施: brentuximab vedotin (Drug)
Brentuximab vedotin + ART
Brentuximab vedotin given on Day 1 and Day 15. ART will be given throughout the study.
干预措施: ART (Drug)
Placebo + ART
Placebo given on Day 1 and Day 15. ART will be given throughout the study.
干预措施: Placebo (Drug)
Placebo + ART
Placebo given on Day 1 and Day 15. ART will be given throughout the study.
干预措施: ART (Drug)
结局指标
主要结局
Number of participants with laboratory abnormalities
时间窗: Approximately 1 year
Number of participants with adverse events (AEs)
时间窗: Through 30 days after last study treatment
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment
Number of participants with dose-limiting toxicities (DLTs) by dose level
时间窗: Up to 30 days
次要结局
- Apparent terminal half-life (t1/2)(Approximately 4 months)
- Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL, with a minimum increase of 50 cells/µL(Approximately 1 year)
- Change from baseline in CD8+ T-cell lymphocyte counts(Approximately 1 year)
- Change from baseline in CD4:CD8 ratio(Approximately 1 year)
- Maximum concentration (Cmax)(Approximately 4 months)
- Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL(Approximately 1 year)
- Trough concentration (Ctrough)(Approximately 4 months)
- Duration of CD4+ T-cell lymphocyte count increases >200 cells/µL(Approximately 1 year)
- Change from baseline in Treg and other T-cell subsets(Approximately 6 months)
- Proportion of subjects with fatal or non-fatal acquired immunodeficiency syndrome (AIDS) related opportunistic disease or death from any cause(Approximately 1 year)
- Area under the concentration-time curve (AUC)(Approximately 4 months)
- Time to maximum concentration (Tmax)(Approximately 4 months)
- Incidence of antidrug antibodies (ADAs)(Approximately 4 months)
- Change from baseline in CD4+ T-cell lymphocyte counts(Approximately 1 year)
- Change from baseline in CD4+ T cell percentage(Approximately 1 year)
- Proportion of subjects with HIV viral load <50 copies/mL(Approximately 1 year)
- Duration of CD4+ T-cell lymphocyte count increases >200 cells/µL with a minimum increase of 50 cells/µL(Approximately 1 year)