Multicenter, National, Prospective, Open Label, Randomized, Pilot, Proof-of-concept Study on the Use of Rilpivirine Plus Darunavir/Cobicistat as Substitutive Agents in Virologic Suppressed Patients
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 1,609
- 试验地点
- 1
- 主要终点
- clinical response
研究概览
简要总结
This study evaluates efficacy and safety of rilpivirine as substitutive agent for the nucleosidic backbone of HAART in virologic suppressed patients when combined with cobicistat-boosted darunavir.
详细描述
HAART is generally based on the combination of three active drugs. Two of them, usually defined the backbone, belong to the nucleosidic analogues class (NRTI). In the last years, drugs of this class have been associated to several long-term adverse events of HAART such as lipoatrophy, cardiovascular diseases, bone and kidney toxicity. Furthermore the need of a triple drug regimen has recently been questioned as maintenance therapy in well controlled chronically treated subjects. In this setting, less drug regimens (LDR) have been proposed. LDR would allow a reduced exposure to drugs and eventually limit drug-drug interactions, drug-related toxicities and would allow treatment simplification so to enhance HAART acceptability, tolerability and persistence.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written signed and dated informed consent to participate in the study must be given by the subject, in accordance with the International Conference of Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E627 and applicable regulations, before completing any procedure related to the study.
- •HIV-1 documented infection
- •Male and female subjects > 18 years of age.
- •Males, or non-pregnant, non-lactating females of childbearing potential, as demonstrated by a negative pregnancy test, who agree to comply with any applicable contraceptive requirements of the protocol. Women of child-bearing potential with a negative pregnancy test at Screening and Day 1 should agree to use one of the following methods: Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IMP, throughout the study, and for at least 2 weeks after; Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide) IUD and male condom Male partner sterilization confirmed and male condom Approved hormonal contraception and male condom Any other method with published data showing that the expected failure rate is <1% per year and use male condo Any contraception method must be used for at least 2 weeks after discontinuation of IMP.
- •Being on a stable therapy for at least 6 months.
- •SBR must be based on any 2NRTI plus a third NNRTI, PI or INI agent. Any possible registered drug is allowed among NRTI (e.g. tenofovir, lamivudine, emtricitabine and abacavir), PI (e.g. lopinavir, atazanavir, darunavir), NNRTI (efavirenz, nevirapine, rilpivirine) or INI (raltegravir, elvitegravir, dolutegravir).
- •Having a fully suppressed HIV replication as documented by 2 prior HIV-RNA tests (at least two months apart) below the detection limit (50 copies/ml).
- •Subjects and investigator must agree that participation in this study is in the best interest of the subject.
排除标准
- •Patients co-infected with HBV
- •Pregnancy or breast feeding.
- •Positive anamnesis for allergy to NNRTI
- •A positive historical genotypic test showing resistance-inducing mutation either toward NNRTIs or PIs
- •History or other evidence of severe illness (malignancy or OI) requiring active treatment and/or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
- •Anticipated need for Hepatitis C virus (HCV) therapy during the study period
- •Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses
- •All conditions and medicinal products listed in contraindications of DRV/c and rilpivirine
- •Subjects with current or prior (previous year) history of alcohol or other substance abuse.
- •Patients who have previously been screened for or enrolled into this study and subsequently withdrawn.
- •Patients having been given investigational drugs within 12 weeks prior to screening.
- •Inability or unwillingness to provide informed consent.
- •Life expectancy < 18 months
研究组 & 干预措施
RPV +DRV/cobi
The experimental receives rilpivirine (a tablet/day) and cobicistat/darunavir co-formulated tablets (a tablet day) since randomization.
干预措施: Rilpivirine + darunavir/cobicistat (Drug)
baseline therapy (CAR)
The control arm continues the baseline therapy (CAR) based on 3 drugs (2 NRTIs) for 24 weeks and then will be switched to receive rilpivirine (a tablet/day) and cobicistat/darunavir co-formulated tablets (a tablet day).
干预措施: Rilpivirine + darunavir/cobicistat (Drug)
结局指标
主要结局
clinical response
时间窗: 48 weeks
proportion of patients with HIV-RNA \< 50 copies/ml
Virological response
时间窗: 24 weeks
proportion of patients with HIV-RNA \> 50 copies/ml (FDA snapshot)
次要结局
- Tolerability (number and proportion of AEs)(48 weeks)
- Bone mineral density(48 weeks)
研究者
Franco Maggiolo
Managing Director
A.O. Ospedale Papa Giovanni XXIII