Efficacy, Safety and Tolerability of Switching to DTG/3TC Single Tablet Regimen From B/F/TAF in Older Persons Living With HIV in Kenya
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 240
- 试验地点
- 2
- 主要终点
- Proportion of participants with virological failure at week 48
研究概览
简要总结
OBJECTIVE:
To assess the efficacy and safety of switch to dolutegravir and lamivudine (DTG/3TC) single tablet regimen from bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in persons living with HIV aged 60 years old or more.
METHODS:
This is a phase 3b, multi-center, open-label, single-arm clinical trial over 96 weeks. The study will take place at two sites in Kenya: Kenyatta National Hospital (KNH) and Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). Study visits will take place at screening, baseline, and weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96 (with a 6-week extension as required for confirming HIV-1 RNA levels). A target of 240 participants from the ongoing B/F/TAF Elderly Switch Study will be enrolled. Eligible participants will be switched from B/F/TAF to DTG/3TC at enrollment and followed up for 96 weeks. The primary endpoint will be the proportion of participants with plasma HIV-1 RNA ≥ 50 copies/mL (Snapshot algorithm) at Week 48. Analysis of the primary endpoint will be performed for the intention to treat - exposed (ITT-E) population using the FDA snapshot method.
详细描述
BACKGROUND:
Three drug regimens for the treatment of HIV are widely used and successful in achieving viral suppression. However, they are associated with various adverse events including renal and bone disease, anaemia, mitochondrial toxicity, and possible association with increased cardiovascular events. Data from the ongoing B/F/TAF Elderly Switch Study has demonstrated high rates of renal insufficiency and osteoporosis in people living with HIV aged 60 years or more, hence the need for safe treatment options. Two drug regimens (2DR) have demonstrated non-inferiority to three drug regimens in patients who are treatment-naïve as well as in those who are virally suppressed on a first-line regimen and potentially have lower toxicity, fewer adverse drug events and a lower drug burden.
OVERALL STRATEGY:
This is a phase 3b, multi-centre, open-label, single-arm clinical trial over 96 weeks describing the efficacy of switching virally suppressed HIV-1 infected adults to DTG/3TC dual therapy from their current B/F/TAF regimen. The primary efficacy endpoint is the proportion of participants with viral load (VL) ≥ 50 copies/ml at week 48.
The study will take place at two sites in Kenya: Kenyatta National Hospital (KNH, the largest teaching and referral hospital in Kenya), and Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH, the largest teaching and referral hospital in the Nyanza region of Kenya). The outpatient HIV clinics at these sites currently provide antiretroviral therapy (ART) to over 15,000 persons living with HIV (PWH) combined. These two sites are currently participating in the B/F/TAF-elderly study.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to understand and comply with the protocol requirements, instructions and restrictions
- •Able and willing to give informed consent
- •Have been randomised to the B/F/TAF arm and completed the B/F/TAF-elderly study. Participants should be on B/F/TAF until day 1 of entry into the current study
- •HIV-1 RNA viral load < 50 copies/ml at screening (within 28 days prior to enrollment)
排除标准
- •Confirmed treatment failure as defined by two consecutive HIV-1 RNA viral loads ≥ 50 copies/ml separated by at least 2 weeks, after at least 6 months on ART or after a documented HIV-1 RNA viral load < 50 copies/ml
- •Using any protocol-defined prohibited medicine where the participant is unwilling or unable to switch to an alternative (see Section 5.
- •under Prohibited medications and non-drug therapies)
- •Evidence of hepatitis B virus (HBV) infection based on the results of testing at screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs) and HBV DNA as follows:
- •Participants positive for HBsAg are excluded;
- •Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status), whether negative or positive for HBV DNA, are excluded;
- •Participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded.
- •Has AST and/or ALT at least 5-times greater than the upper limit of normal
- •Severe hepatic impairment (Class C) as determined by Child-Pugh classification
- •Has an estimated creatinine clearance (CrCl) below 30 ml/min (as estimated using the Cockcroft-Gault estimate for glomerular filtration rate)
- •Documented opportunistic infection within 4 weeks prior to the study enrolment
- •Any condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the study
- •Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment). Participants who are at least 7 days post completed treatment are eligible.
- •History or presence of allergy or intolerance to the study treatment or their components or drugs of their class or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
- •Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia.
- •Participants who in the investigator's judgment, poses a significant suicidality risk. Participant's history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk
- •Any evidence of any major 3TC resistance associated mutations (M184V/I and/or K65R and/or MDR) or presence of any major INSTI resistance associated mutation
研究组 & 干预措施
Switch to DTG/3TC 2DR
Participants will be switched from B/F/TAF to a fixed-dose combined DTG/3TC pill each containing 50mg of dolutegravir and 300mg of lamivudine taken once daily for the duration of the study
干预措施: DTG/3TC (Drug)
结局指标
主要结局
Proportion of participants with virological failure at week 48
时间窗: 48 weeks
Number and proportion of participants with plasma HIV-1 RNA ≥ 50 copies/mL as per the FDA Snapshot algorithm) at Week 48
次要结局
- Change in lipid parameters(24, 48 and 96 weeks)
- Change in fasting blood sugar(48 and 96 weeks)
- Patient satisfaction as measured using the HIV Treatment Satisfaction Questionnaire - Status version (HIVTSQs) which scores 10 variables on a 7-point likert score ranging from 0 to 6 with a higher score representing a better outcome(24 and 96 weeks)
- Proportion of participants with virological failure at week 96(96 weeks)
- Proportion of participants with virological failure at week 24(24 weeks)
- Proportion of participants with treatment success(24, 48 and 96 weeks)
- Change in CD4(24, 48 and 96 weeks)
- Number of participants with HIV disease progression(24, 48 and 96 weeks)
- Change in weight(24, 48 and 96 weeks)
- Incidence of adverse events(24, 48 and 96 weeks)
- Change in blood pressure(24, 48 and 96 weeks)
- Change in fat and lean mass(96 weeks)
- Weight gain of 10% or more(48 and 96 weeks)
- Change in the Atherosclerotic Cardiovascular Disease (ASCVD) score which is a 10-year risk for ASCVD estimation with <5% being low risk and a higher percentage representing increased ASCVD risk(48 and 96 weeks)
- Change in patient satisfaction as measured using the HIV Treatment Satisfaction Questionnaire - Change version (HIVTSQc) which scores 10 variables on a 7-point likert score ranging from -3 to +3 with a higher score representing a better outcome(48 weeks)
- Health related quality of life as measured using the World Health Organization Quality of Life brief questionnaire in HIV population (WHOQOL-HIV BREF) tool(48 and 96 weeks)
- HIV drug resistance(24, 48 and 96 weeks)
- Treatment-related adverse events(24, 48 and 96 weeks)
- Change in urinary protein/creatinine ratio(48 and 96 weeks)
- Change in beta-2 microglobulin(48 and 96 weeks)
- Change in retinol binding protein(48 and 96 weeks)
- Change in cystatin C(48 and 96 weeks)
- Change in the estimated glomerular filtration rate as measured using the 2021 CKD-EPI creatinine calculator(48 and 96 weeks)
- Change in the estimated glomerular filtration rate as measured using the 2021 CKD-EPI creatinine-cystatin C calculator(48 and 96 weeks)
- Change in AST, ALT and gamma-glutamyltransferase (GGT)(48 and 96 weeks)
研究者
Loice Achieng Ombajo
Principal Investigator
University of Nairobi