A Pilot Phase II Study of a Nucleoside Sparing Regimen of Dolutegravir + Atazanavir/r in HIV-1 Infected Patients With Detectable Viremia (DOLATAV Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Primary endpoint - The proportion of patients with undetectable HIV RNA viral load ( < 50 copies/ml) at week 24
研究概览
简要总结
Research ipotesis is to assess the efficacy and safety of a nucleos(t)ide sparing regimen of atazanavir/ritonavir 300 mg /100 mg QD + Dolutegravir 50 mg QD for the management of virological failure in HIV-1 infected patients.
The Primary Objective is to explore the 24-week efficacy of a nucleos(t)ide sparing regimen of atazanavir 300 mg QD/ ritonavir 100 mg QD + Dolutegravir 50 mg QD for the management of virologic failure in HIV-1 infected, integrase inhibitor-naïve subjects.
详细描述
Study design;
• 24-week prospective, single-arm, monocentric, open label, pilot study Participants will be seen at screening, baseline, day 8 and at week 4, 8, 12, 16, 24.
At each visit the following evaluations will be performed:
- clinical assessment.
- routine laboratory tests (hematological tests and clinical chemistry) including hemochromocytometric examination with leukocytic formula, creatinine, creatine kinase, transaminases, phosphorus, calcium, alkaline phosphatase, total and direct bilirubin, gammaGT, uric acid, lactate dehydrogenase, urine analysis, glucose, lipid profile, HIV-RNA and CD4 cell counts.
Additional blood samples will be collected at each visit for storage and further determinations.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with age more than 18 years
- •Willing and able to provide informed consent
- •Failing a stable (at least 3 months) antiretroviral therapy (HIV-RNA more than 200 copies/ml)
- •Any CD4 cell count
- •Virus susceptible to atazanavir, defined as a genotypic mutation score inferior to 15 according to the HIV drug resistance database (Stanford University)
- •No previous documented virologic failure during an atazanavir-containing regimen
- •No previous exposure to integrase inhibitors
- •Absolute neutrophil count (ANC) more than 500/mm3
- •Haemoglobin more than 8.0 g/dL
- •Platelet count more than 60,000/mm3
- •e-GFR> 60 ml/min using CKD-EPI equation
排除标准
- •Active AIDS-defining condition at Screening
- •Serious illness requiring systemic treatment and/or hospitalization
- •Current use of immunomodulant or immunosuppressive drugs
- •Requirement for any concomitant medications that are prohibited with any study drugs (protocol section 3.6)
- •History or presence of hypersensitivity to any of the active substances or to the excipients
- •Alanine aminotransferase (ALT) more than 5 times the upper limit of normal (ULN), OR ALT more than 3xULN and bilirubin more than 1.5xULN (with more than 35 percent direct bilirubin)
- •Subjects positive for Hepatitis B at screening (HBsAg positive)
- •Subjects with anticipated need for Hepatitis C virus (HCV) therapy during the study
- •Presence of moderate or severe hepatic impairment (defined as a Class B or C at Child Pugh Classification) or presence of unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice) or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Pregnancy or pregnancy wish; breastfeeding
- •Moreover, all clinical conditions reported as an absolute contraindication in the summary of product characteristics of the study drugs, will be considered as exclusion criteria.
研究组 & 干预措施
Open label single arm
Introduction of treatment regimen with atazanavir 300mg qd + ritonavir 100mg qd + dolutegravir 50mg qd
干预措施: atazanavir 300 mg + ritonavir 100 mg + dolutegravir 50 mg (Drug)
结局指标
主要结局
Primary endpoint - The proportion of patients with undetectable HIV RNA viral load ( < 50 copies/ml) at week 24
时间窗: 24 weeks
The proportion of patients with undetectable HIV RNA viral load ( \< 50 copies/ml) at week 24.
次要结局
- Change from baseline CD4 cell counts (Immunological efficacy)(4,8,12,16,24 weeks)
- Time to achieve undetectability (Virologic efficacy)(Day 8, weeks 4,8,12,16,24)
- Atazanavir and Dolutegravir Ctrough (PK evaluation)(Day 8, weeks 4,8,12,16,24)
- proportion of patient with undetactable HIV RNA at week 4 (Virologic efficacy)(4 week)
- Occurrence of genotyping resistance mutations for PI and INSTI in isolates from patients with virological failure.(24 week)
- Proportion of patients with adverse events (safety and tolerability).(Day 8, weeks 4,8,12,16,24)
- Change in ECG parameters (safety and tolerability)(24 week)
- Changes in lipid, clearance creatinine and glycemic profile from baseline (safety and tolerability)(weeks 4,8,12,16,24)
- Adherence evaluation(8,12,16,24 weeks)
研究者
Castagna Antonella
Sub Investigator
IRCCS San Raffaele