A Phase IV 48 Week, Open Label, Pilot Study of Darunavir Boosted by Cobicistat in Combination With Rilpivirine to Treat HIV+ Naïve Subjects (PREZENT)
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Proportion of patients with plasma HIV-1 RNA <50 copies/mL
研究概览
简要总结
Current HIV treatment guidelines recommend the use of triple-drug therapy (two nucleoside reverse transcriptase inhibitors and either a protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or an integrase inhibitor) for the treatment of antiretroviral (ARV)-naïve patients. With the introduction of highly active antiretroviral therapy (HAART), patients with HIV are living much longer. With the increasing lifespan of persons with HIV, long-term complications from therapy as well as the occurrence of co-morbidities with aging have prompted HCPs to re-think the current treatment paradigm and consider novel combinations of ARVs. All of the currently approved HIV antiretrovirals have been implicated in causing long-term toxicities; however the greatest body of evidence for long-term metabolic effects has implicated the nucleoside reverse transcriptase (NRTI) class. By utilizing a non-NRTI treatment regimen, it is hypothesized that many of these long-term metabolic effects (renal toxicity, bone loss, body fat changes) can be delayed or avoided altogether. The clinical data on novel combinations is currently limited but rapidly growing and has included several combinations that have utilized darunavir. This study will be the first of its kind using the unique combination of darunavir/cobicistat and rilpivirine. Currently, this drug combination is not a recommended option for first time treatment of HIV
详细描述
This is a Phase IV, 48-week, open-label, pilot study in 30 ARV-naïve patients examining the safety, viral response, and tolerability of darunavir/cobicistat in combination with rilpivirine once daily for the treatment of HIV in treatment-naïve patients.
Thirty subjects meeting the inclusion criteria for study will be selected at a single site. All 30 subjects will receive darunavir/cobicistat 800/150mg in combination with rilpivirine 25 mg once daily at study onset and will be followed for 48 weeks after starting study medications. Virologic failure will be defined as failure to achieve HIV-1 RNA <50 copies/mL by week 24 of therapy, or in patients with baseline HIV-1 RNA >100,000 copies/mL, failure to achieve 1 log10 reduction in HIV-1 RNA by week 24. Confirmed virologic failure will be defined as two consecutive HIV RNA levels ≥50 copies/mL after suppression to <50 copies/mL for two consecutive measurements. Patients with confirmed virologic failure will be discontinued from the study and switched to a new antiretroviral treatment regimen.
Patients who have decided to initiate treatment after consultation with their physician and after careful review of the Department of Health and Human Services (DHHS) guidelines for treatment will be considered for enrollment as research subjects. Individuals considered for enrollment providing informed consent (See Appendix A) will be screened and, if eligible, enrolled in the study. Adherence to study regimen and symptoms of hypersensitivity reactions will be monitored by self-report at each study visit. Adherence will be assessed using the standard ACTG Adherence Questionnaire II (See Appendix B), either over the telephone or during a clinic visit. Those patients reporting problems with adherence will be counseled and monitored closely every 4 weeks at clinic visits with phone consultation bi-weekly until adherence improves. If despite counseling, adherence is not maintained, patients will be discontinued from the study due to increased risk of drug resistance. AEs will be monitored closely to determine if appropriate management affects tolerability and adherence, i.e., prescribing anti-emetic or anti-diarrhea medications for nausea and diarrhea, respectively. Patients will be counseled on the importance of adherence at every study visit.
Hematology, blood chemistry, liver function tests, virologic and immunologic measurements will be obtained at baseline (week 0), weeks 4, 12, 24, 36, and 48. In addition to blood chemistry evaluations, fasting blood samples will be obtained at baseline and weeks 24 and 48 for triglycerides, total cholesterol, direct HDL cholesterol and LDL cholesterol. Pancreatic amylase and serum lipase levels will be determined if serum amylase results are >2x ULN (see Section 5.4.2 Laboratory Evaluations).
In a subset of 12 subjects at their baseline and with at least 24 weeks exposure to darunavir and rilpivirine a lumbar puncture will be performed to obtain a sample of CSF for viral load, cell count and darunavir and rilpivirine concentration.
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
- •HIV-1 RNA ≥ 5000 copies/mL by PCR
- •≥ 18 years of age
- •Cognitive ability to understand and provide written informed consent and willingness to participate in and comply with the study protocol
- •Less than 7 days of prior ART with any licensed or investigational compound
- •Patient does not currently have or has not been treated for an active opportunistic infection (OI) consistent with CDC definition (Appendix C) within 30 days of screening
- •Vital signs, physical examination and laboratory results do not exhibit evidence of acute illness
- •A female is eligible to enter and participate in this study if she is of non child bearing potential or child bearing potential, has a negative serum pregnancy test at screen.
- •Exclusion Criteria
- •Patient with active AIDS-defining opportunistic infection or disease according to the 1993 CDC AIDS surveillance definition (Clinical Category C) in the 30 days prior to baseline and that, in the opinion of the investigator, would preclude the patient from participating in the study (See Appendix C).
- •Patient has none of the following darunavir-associated RAMs: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V
- •Having documented genotypic evidence of NNRTI resistance at screening or from historical data available in the source documents, i.e. at least one of the NNRTI rams from the following list; K101E, K101P, E138A, E138G, E138K, E138R, E138Q, , V179L, Y181C, Y181I, Y181V, Y188L, H221Y, F227C, M230I, M230L, or the combination of the K103N and L100I.
- •History of active substance abuse, excluding cannabis, or psychiatric illness that, in the opinion of the investigator, would preclude compliance with protocol, dosing schedule and assessments.
- •Patient is either pregnant at time of screening evaluation or breast-feeding.
- •Patient, in the opinion of the investigator, is unlikely to be able to complete the 48-week dosing period and protocol evaluations and assessments or adhere to the study drug regimen.
- •Patient suffers from a serious medical condition, such as diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction, which in the opinion of the investigator would compromise the safety of the patient
- •Patient has malabsorption syndrome or other gastrointestinal dysfunction, which may interfere with drug absorption or render the patient unable to take oral medication.
- •Patient is undergoing interferon therapy for HCV or anticipates undergoing therapy during the course of this trial
- •HBV co-infection
- •Patient has any of the following laboratory results within 30 days prior to the first dose of study medication:
- •Hemoglobin concentration < 8.0 g/dL
- •Absolute neutrophil count < 750 cells/mm3
- •Platelet count <50,000 cells/ mm3
- •Aminotransferase (AST, ALT) >3 times ULN
- •Serum creatinine >1.5 times the Upper Limits of Normal (ULN)
- •Patients with severe hepatic impairment
- •Patient has required treatment with radiation therapy or cytotoxic chemotherapeutic agents within 4 weeks prior to entry, or has an anticipated need for these agents within the study period.
排除标准
- 未提供
研究组 & 干预措施
Darunavir/ cobicistat and Rilpivirine
Single arm study:
Darunavir/ cobicistat 800/ 150 mg tablet once daily taken with food Rilpivirine tablet 25 mg once daily taken with food
干预措施: darunavir/cobicistat (Drug)
Darunavir/ cobicistat and Rilpivirine
Single arm study:
Darunavir/ cobicistat 800/ 150 mg tablet once daily taken with food Rilpivirine tablet 25 mg once daily taken with food
干预措施: rilpivirine (Drug)
结局指标
主要结局
Proportion of patients with plasma HIV-1 RNA <50 copies/mL
时间窗: up to weeks 48
次要结局
- Proportion of patients with plasma HIV-1 RNA <400 copies/mL at each time point evaluated(At week 4, week 12, week 24, week 36, week 48)
- Number of weeks until HIV RNA <400 copies/mL and <50 copies/mL, respectively(At week 4, week 12, week 24)