Pilot Study: Single Arm, Multi-site, Open-label Study to Assess the Effectiveness of Peg-IFN-a2b in Decreasing the Levels of Cell-associated Integrated Viral DNA in HIV Chronic Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 3
- 主要终点
- Change From Baseline in Copies of HIV DNA Per CD4+ T Cell at Week 24
研究概览
简要总结
We propose to test our primary hypothesis that treatment with Peg-IFN-α-2b will result in a decrease in integrated HIV DNA in peripheral blood and tissue in chronically HIV-infected immune-reconstituted individuals (see section 3.1) in a prospective, interventional, 1-arm, open label clinical trial. To this end, we propose to enroll 25 HIV-1-infected subjects (please refer to power calculations in section 10.1 below) currently stably suppressed (> 1y with VL < 50 copies/ml) on ART and with CD4 count > 450 cells/µl.
We hypothesize that 20 weeks of treatment with Peg-IFN-alpha-2b, in the presence of HIV reactivation (i.e.: ART interruption), will result in activation of intrinsic and/or immune-mediated anti-HIV mechanisms resulting in a decrease in the levels of viral reservoir in chronically HIV-infected, immune-reconstituted individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-65 years of age
- •Body weight between 125 and 299 lbs
- •Confirmed diagnosis of HIV-1 infection by western blot or by a documented HIV-1 viral load
- •Currently receiving ART and on ART for > 1 year
- •VL < 50 copies/ml for ≥ 1 year, with at least 2 measurements in the previous year, 1 viral "blip" with VL< 400 copies/ml allowed
- •HIV viral load of <50 copies/ml at screening.
- •CD4 >450 cells/µL at screening.
- •A negative ECG if >45yrs men/>55yrs women years of age or if below these years of age but with two added risk factors for coronary artery disease [smoking, hypertension (BP >140/90 or on antihypertensive medications), low HDL (<40 mg/dL), family history of premature CHD (<55 yrs males/<65 females)] or a Framingham score > 15% (men) or 10% (women))
排除标准
- •Confirmed clinical history of developing resistance to ART regimens that resulted in treatment changes
- •Receiving didanosine as part of the participant's ART regimen at the time of screening
- •Ongoing treatment with Isoniazide, pyrazinamide, Rifabutin, Rifampicin, Diadenosine Ganciclovir, Valgancyclovir, Oxymetholone, Thalidomide or Theophylline.
- •Use of any investigational drug within 30 days prior to screening
- •History or current use of immunomodulatory therapy for over 2 weeks during the 6 months prior to enrollment, including, but not limited to: IFN-alpha or gamma (recombinant or pegylated), systemic corticosteroids (nasal or pulmonary steroids will be allowed; systemic cancer chemotherapy/irradiation; cyclosporin; tacrolimus (FK-506); OKT-3; any Interleukin, including IL-2; cyclophosphamide; methotrexate; IVIG (gamma globulin); G/M-CSF; hydroxyurea; thalidomide; pentoxifylline; thymopentin; thymosin; dithiocarbonate; polyribonucleotide.
- •History of adverse or allergic reactions to any type-1 interferon (e.g. IFN-alpha2a, IFN-α2b, IFN-beta)
- •History of severe depression, or ongoing moderate depression determined by PHQ-9 at screening
- •Type I diabetes mellitus, or type II diabetes mellitus that is not controlled with oral agents and/or insulin.
- •Prior diagnosis of multiple sclerosis or other neurodegenerative disorders
- •Significant co-existing lab abnormalities including:
- •Anemia (Hgb <9.1 mg/dl men, <8.9 mg/dl women)
- •WBC <2000 cells/µl
- •Absolute neutrophil count (ANC) <1200 cells/ µl
- •Platelet count <60,000 cells/ µl
- •Liver disease (AST/ALT > 2.5x, Total Bilirubin > 1.5x upper limits of norm (ULN), or Total Bilirubin >3x ULN if receiving indinavir OR Atazanavir)
- •Renal disease (creatinine > 2x upper normal limits or creatinine clearance <60mg/dl (by Crockoff-Gault)
- •Chronic HCV infection (HCV viremia), or HBV Ag positive and/ or HBV viremia (Notice: subjects with prior HCV infection with a documented sustained virologic response with treatment finishing >1 year prior to screening are eligible for enrollment).
- •Liver cirrhosis or hepatic decompensation with Child Pugh score > 6
- •History of major organ transplantation with an existing functional graft.
- •Evidence of OI or other active infectious diseases or active malignancies
- •Active Autoimmune diseases, including autoimmune hepatitis
- •History of retinopathy or clinically significant ophthalmologic disease on eye exam performed within 6 months prior to initiation of IFN
- •Pregnancy, actively attempting to become pregnant, or breastfeeding
- •Body weight under 125 lbs or over 300 lbs
- •Other conditions, such as active drug/alcohol abuse or dependence which would interfere with study compliance
研究组 & 干预措施
Interferon alpha
pegylated Interferon alpha 2b (Pegintron) 1 µg/kg per week, 20 weeks
干预措施: Pegylated Interferon alpha 2b (Drug)
结局指标
主要结局
Change From Baseline in Copies of HIV DNA Per CD4+ T Cell at Week 24
时间窗: Week 3 and 24
Difference in copies of HIV DNA per CD4+ T cell between baseline and week 24, assessed by Alu-HIVgag polymerase chain reaction
次要结局
未报告次要终点
研究者
Luis Montaner
Professor
The Wistar Institute