A Phase 2a, Randomized Study of Romidepsin With or Without 3BNC117 to Evaluate the Effects on the HIV-1 Reservoir (ROADMAP)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 3
- 主要终点
- Days to Viral Rebound During Analytical Treatment Interruption (ATI)
研究概览
简要总结
The aim of this protocol is to evaluate the effects of romidepsin plus 3BNC117 or romidepsin alone on delaying or preventing viral rebound in ART-treated HIV-1-infected individuals during an analytical interruption of ART.
详细描述
This is a randomized interventional phase 2a trial of 3BNC117 and romidepsin in human immunodeficiency (HIV-1) infected patients on ART, conducted as a multi-center study at the Department of Infectious Diseases, Aarhus University Hospital, Denmark, the Rockefeller University Hospital, USA, and the University Hospital of Cologne, Germany.
Participants will be randomized 1:1 in a non-blinded fashion to receive one of two regimens:
A) Two treatment cycles each consisting of one 3BNC117 infusion (30mg/kg) + three romidepsin infusions (5mg/m2); or
B) Two treatment cycles each consisting of three romidepsin infusions (5mg/m2).
ART will be discontinued 16 weeks after the start of the second treatment cycle (analytical treatment interruption, ATI) and subjects will be monitored weekly for safety and viral rebound. The targeted enrollment is 30 subjects (15 per arm).
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
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults age 18-65 years with documented HIV-1 infection
- •CD4+ T-cell count >500 cells/mm3 at screening
- •On ART for a minimum of 24 months and HIV-1 RNA plasma level of < 50 copies/ml by standard assays for at least 18 months (a single viral load measurement > 50 but < 500 copies/ml during this time period is allowable).
- •Individuals on protease inhibitor or NNRTI-based regimens, or regimens containing cobicistat must be willing to switch to an integrase-inhibitor-based regimen (raltegravir or dolutegravir) prior to enrollment.
排除标准
- •Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the investigators within the last 6 months
- •Pregnancy as determined by a positive urine or serum beta-hCG.
- •Participant unwilling to use two reliable contraception methods (i.e. condom with spermicide, diaphragm with spermicide, progestin-only containing intrauterine device (IUD) (eg, Mirena, Implanon, Nuva Ring), non-estrogen containing formulations of hormonal birth control drugs with condom) for the study duration.
- •Currently breast-feeding.
- •History of resistance to 2 or more classes of antiretroviral medications
- •Any medical, psychiatric, social, or occupational condition that, as judged by the investigators, would interfere with the evaluation of study objectives (such as severe alcohol or drug abuse, dementia).
- •Acute or chronic hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
- •A history of AIDS-defining illness within 3 years prior to enrollment.
- •History of B-cell lymphoma, including CNS lymphoma
- •CD4 nadir < 200 cells/mm3
- •History of significant coronary artery disease, myocardial infarction, percutaneous coronary intervention with placement of cardiac stents, or family history of sudden death at age < 50 years.
- •ECG at screening that shows QTc >450 msec when calculated using the Fridericia formula from either lead V3 or V4, pathological Q-waves (Q-wave > 40 msec or depth > 0.4-0.5 mV), evidence of a ventricular pre-excitation syndromes, complete or incomplete LBBB or RBBB, second or third degree heart block, QRS duration > 120 msec, or bradycardia defined by sinus rate < 50 bps
- •Use of QT-prolonging medication, renal or hepatic disease, structural heart disease or left ventricular dysfunction
- •Any symptomatic or asymptomatic arrhythmia excluding sinus arrhythmia and bradycardia ≥ 50 bps.
- •Laboratory abnormalities in the parameters listed below:
- •Absolute neutrophil count ≤ 1,000 cells/μl
- •Hemoglobin < 11 gm/dL
- •Platelet count < 125,000 cells/μl
- •Alanine Aminotransferase (ALT) ≥ 1.25 x ULN
- •Aspartate Aminotransferase (AST) ≥ 1.25 x ULN
- •Total bilirubin > 1.0 ULN
- •Creatinine > 1.0 ULN
- •Any vaccination within 14 days prior to 3BNC117 administration
- •Receipt of any therapeutic HIV vaccine in the past
- •Receipt of any monoclonal antibody or HDAC inhibitor of any kind in the past.
- •Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
研究组 & 干预措施
Group A
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
干预措施: 3BNC117 (Drug)
Group A
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
干预措施: Romidepsin (Drug)
Group B
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
干预措施: Romidepsin (Drug)
结局指标
主要结局
Days to Viral Rebound During Analytical Treatment Interruption (ATI)
时间窗: Week 24 to Week 36
Viral rebound is defined as HIV-1 RNA ≥ 200 copies/mL on 2 consecutive measurements during ATI. If viral rebound occurs, the date of the first measurement of HIV-1 RNA ≥ 200 copies/mL will be defined as "date of viral rebound
次要结局
- Number of of Adverse Events (AE), Serious Adverse Events (SAE), and Serious Unexpected Serious Adverse Reactions (SUSAR).(48 weeks)
- Change in the Size of the Proviral HIV-1 Reservoir(baseline and week 24)
- Plasma HIV-1 RNA(48 weeks)