An Open-Label, Multi-Centre, Randomised, Switch Study to Evaluate the Virological Efficacy Over 96 Weeks Of 2-Drug Therapy With DTG/RPV FDC in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects Virologically Suppressed With Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Resistance Mutation K103N
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 140
- 试验地点
- 29
- 主要终点
- Number of Participants With and Without Virological Suppression
研究概览
简要总结
HIV-1 infected subjects that experience virological failure while on non nucleoside reverse-transcriptase inhibitors (NNRTIs), including those with the K103N mutation, are usually switched to a boosted Protease Inhibitor (PI)-based regimen or other antiretroviral (ARV) combinations. The same is true for subjects who need to start antiretroviral therapy and have acquired virus that is already resistant to antiretrovirals. These "second line" combinations are often associated with numerous issues that can have a potential impact on the quality of life (QoL) of these patients. Therefore a simpler and better tolerated alternative second line treatment option would be a useful tool for the clinical management of these patients.
The aim of this study is to assess the efficacy and tolerability of a dual combined therapy of Dolutegravir (DTG) 50 mg Once Daily (OD) + Rilpivirine (RPV) 25 mg OD in virologically suppressed participants with previous virological failure with NNRTIs and having the clinically significant mutation K103N. The secondary objective of the study is to assess whether a simplification of the treatment in terms of pill burden, long term metabolic toxicity and potential for drug interactions improves the QOL of the participants. The study will also evaluate DTG & RPV concentrations in the blood plus changes in cell associated virus.
In order to compare the first line treatment (boosted PI and/or other antiretroviral combinations) and the DTG+RPV combination, two thirds of study participants will be switched to DTG+RPV immediately and receive DTG+RPV for 96 weeks. The other third will be switched after 48 weeks of continuing on their first line treatment and receive DTG+RPV for 48 weeks. All participants will then be followed up for a further 30 days. Participants will be recruited from sites across Europe, and randomised onto either arm of the study. After randomisation, participants will attend approximately 10 visits over the course of two years.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
DTG/RPV FDC Regimen
One combined Dolutegravir 50mg /Rilpivirine 25mg FDC tablet taken orally once daily
干预措施: Dolutegravir & Rilpivirine 2 drug fixed dose combined therapy (Drug)
Continued ART Regimen
Patients will continue the current boosted PI regimen (or other antiretroviral combination) for 48 weeks. Patients will then be switched to one combined Dolutegravir/Rilpivirine FDC tablet taken orally once daily for 48 weeks.
干预措施: Dolutegravir & Rilpivirine 2 drug fixed dose combined therapy (Drug)
结局指标
主要结局
Number of Participants With and Without Virological Suppression
时间窗: 48 weeks
Virological Suppression is defined as \<50 copies/ml HIV RNA
次要结局
- Number of Participants With and Without Virological Suppression(week 96)
- Changes in Blood Cell Counts - Red Blood Cells(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Blood Cell Counts - White Blood Cells(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Blood Cell Counts - Platelets(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Blood Cell Counts - Haemoglobin(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Change From Baseline in Sodium(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Liver Levels - Bilirubin(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Liver Levels - Alanine Aminotransferase (ALT)(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Renal Markers - Creatinine Clearance (Estimated Glomerular Filtration Rate(eGFR))(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Change From Baseline in Glucose(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Renal Markers - Creatinine(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Bone Markers - Alkaline Phosphatase(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Fasting Lipids From Baseline - Total Cholesterol(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Fasting Lipids From Baseline - High Density Lipoprotein (HDL)(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Quality of Life Health Status Score(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Patient Satisfaction - HIV Treatment Satisfaction Questionnaire (HIVTSQs)(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Number of Participants With Adverse Events - Baseline to Week 48(Baseline to week 48)
- Number of Drug Drug Interactions(Baseline, week 24, week 48, week 96)
- Changes in Fasting Lipids From Baseline - Triglycerides(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Fasting Lipids From Baseline - Low Density Lipoprotein (LDL)(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Vital Signs From Baseline - Systolic Blood Pressure(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Vital Signs From Baseline - Diastolic Blood Pressure(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Vital Signs From Baseline - Pulse Rate(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Changes in Pittsburgh Sleep Quality Index (PSQI)(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Number of Participants With Adverse Events - Week 48 to Week 96(From Week 48 to week 96)
- Change From Baseline in CD4(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Change From Baseline in CD8 Cell Count(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Change From Baseline in Body Weight(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)
- Change From Baseline in BMI(Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96)