NCT03945981已完成3 期
A Phase 3b Multi-center, Open Label, Single Arm, 52-week Study, Evaluating the Feasibility, Efficacy and Safety of Rapid Test and Treat Intervention in Newly Diagnosed HIV-1 Infected Adults Using a Fixed Dose Combination of Dolutegravir Plus Lamivudine (DOVATO) as a First Line Regimen
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 131
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) Regardless of Antiretroviral Therapy (ART) Regimen at Week 24 by ITT-E Missing = Failure Analysis
研究概览
简要总结
Early initiation of antiretroviral therapy (ART) reduces morbidity and mortality for individuals infected with HIV. Suppressing viral replication with ART also reduces the potential for transmission of HIV. Hence, ART is recommended for all persons with HIV viremia regardless of cluster of differentiation 4 (CD4) count. This is an open-label single arm which will evaluate the feasibility, efficacy and safety using a fixed dose combination (FDC) of Dolutegravir (DTG) plus Lamivudine (3TC) as a first line regimen of a rapid Test and Treat model of care over 48 weeks. Participants with new and confirmed diagnosed HIV-1 who are willing to start study treatment immediately following diagnosis will receive 50 milligram (mg) DTG + 300 (mg) 3TC FDC as first line therapy without waiting for screening laboratory results, at the Screening/Day 1 Visit. The total duration for the study will be 52 weeks and 4 weeks of follow up period if required. This study will be conducted in United States (US) with approximately 120 participants.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible participants must be able to understand and comply with protocol requirements, instructions, and restrictions.
- •Eligible participants must be likely to complete the study as planned.
- •Eligible participants must be considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g. no active problematic substance abuse, acute major organ disease, or potential long-term work assignments out of the country).
- •Participant must be more than or equal to 18 at the time of signing the informed consent.
- •Participants must have a new and confirmed diagnosis of HIV-1 infection and are willing to initiate ART immediately (or, for those participants referred from another site, within 14 days of initial diagnosis at the external clinic/testing center).
- •Participant must have an initial positive rapid HIV test and participant has a second positive confirmatory rapid HIV test, using a test kit from a different manufacturer than the first test or participant has been identified as HIV-1 infected using an FDA-approved 4th generation assay antigen/antibody combination immunoassay or 3rd generation immunoassay that detects and differentiates HIV-1 and HIV-2 antibodies; participant has a confirmatory HIV western blot or an HIV-1 RNA or participant has a positive FDA-approved 4th generation assay and a positive 3rd generation immunoassay that detects and differentiates HIV-1 and HIV-2 antibodies.
- •Antiretroviral-naïve. Participants who received HIV post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP) in the past are allowed as long as the last PEP/PrEP dose was more than 6 months from HIV diagnosis or there is documented HIV seronegativity at least 2 months after the last prophylactic dose and prior to the date of HIV diagnosis.
- •Male and/or female participants.
- •Participants who are female at birth are eligible to participate if at least one of the following conditions applies: Not pregnant [as confirmed by a negative urine human chorionic gonadotropin (hCG) test at Screening/Day
- •Pregnant and post the first trimester (the physician and patient should decide whether enrolling in this study is in the participants best interest during the consent process)
- •Not a participant of childbearing potential (POCBP) or a POCBP agrees to follow the contraceptive guidance, is currently taking hormonal contraceptives and continues for at least 2 weeks after the last dose of study medication. Participants who are female at birth and who are in the following categories are not considered POCBP, premenarchal, premenopausal female with one of the following: documented hysterectomy, documented bilateral salpingectomy, documented bilateral oophorectomy or postmenopausal, a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in participants who are female at birth and not using hormonal contraception or hormonal replacement therapy (HRT); participants who are female at birth on HRT and whose menopausal status is in doubt will be required to use one of the non-hormonal highly effective contraception methods if they wish to continue their HRT during the study.
- •Participants who are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
排除标准
- •Participants who are breastfeeding, plan to become pregnant or breastfeed during the study.
- •Participants who are in their first trimester of pregnancy.
- •HIV-1 drug resistance genotype test results are known prior to Screening/Day
- •Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease except for esophageal candidiasis and cutaneous Kaposi's sarcoma not requiring systemic therapy.
- •Participants with known or suspected Hepatitis B infection.
- •Participants with known or suspected severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Participants with known moderate to severe renal impairment (creatinine clearance less than 30ml/minute per 1.73 square meter);
- •Participant with ongoing malignancy other than basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study Medical Monitor for inclusion of the participant.
- •Participants who in the investigator's judgment, poses a significant suicidality risk.
- •Participants with any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
- •Participants with substance abuse disorders or social restraints that the Investigator considers to be possible deterrents to successful initiation of ART.
- •Participants with history or presence of allergy or intolerance to the study drugs or their components.
- •Participants with treatment with any of the following agents within 28 days of the first dose of study treatment, radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
- •Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.
- •Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study treatment.
研究组 & 干预措施
Participants receiving Dolutegravir + Lamivudine FDC
Experimental
Participants will receive DTG 50mg and 3TC 300 mg FDC tablet orally once daily (OD) with or without food
干预措施: Dolutegravir + Lamivudine FDC (Drug)
结局指标
主要结局
Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) Regardless of Antiretroviral Therapy (ART) Regimen at Week 24 by ITT-E Missing = Failure Analysis
时间窗: At Week 24
Participants were classified as "HIV-1 RNA \<50 c/mL" using an ITT-E missing = Failure analysis. Participants were classified as 'HIV-1 RNA \< 50 c/mL' if the last viral load within the Week 24 visit window was \<50/c/mL, regardless of the ART regimen they were on at the time of viral load assessment (in other words switch from DTG plus 3TC fixed-dose combination \[FDC\] to another ART was not penalized) and as HIV-1 RNA \>= 50 c/mL in all other cases (i.e. last viral load within Week 24 visit window \>= 50 c/mL, on study but having missing viral load data at Week 24, discontinued early from study due to lost to follow-up (LFU), withdrew consent or any other reason). Confidence intervals (CI) were calculated based on the Exact Clopper-Pearson method. Percentage of participants with plasma HIV-1 RNA \< 50 c/mL based on ITT-E missing = Failure analysis at Week 24 are presented.
次要结局
- Percentage of Participants With Plasma HIV-1 RNA <50 c/mL Using Food and Drug Administration (FDA) Snapshot Algorithm(At Week 24 and Week 48)
- Number of Participants With Any Serious Adverse Events (SAEs) and Any Common (>=2%) Non-serious Adverse Events (Non-SAEs) Under Treatment With DTG + 3TC FDC(Up to Week 48)
- Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities Under Treatment With DTG + 3TC FDC(Up to Week 48)
- Number of Participants Who Discontinued the Study Treatment (DTG+3TC FDC) Due to Drug-related AEs(Up to Week 48)
- Change From Baseline in CD4+/CD8+ Cell Count Ratio for Participants Under Treatment With DTG + 3TC FDC(Baseline (Day 1) and Week 24 and Week 48)
- Percentage of Participants With Plasma HIV-1 RNA <50 c/mL Regardless of ART Regimen at Week 48 by ITT-E Missing = Failure Analysis(At Week 48)
- Change From Baseline in Cluster of Differentiation (CD4+) Cell Counts for Participants Under Treatment With DTG + 3TC FDC(Baseline (Day 1) and Week 24 and Week 48)
- Time to Viral Suppression (HIV-1 RNA<50 c/mL) for Participants Who Had HIV-1 RNA >= 50 c/mL at Baseline(Up to Week 48)
- Number of Participants Who Changed First Line Regimen of DTG + 3TC FDC Due to Baseline Laboratory Results or HIV-1 Resistance Mutation Results(Up to Week 48)
- Number of Participants With Treatment-emergent Genotypic Resistance(Up to Week 48)
- Number of Participants With Treatment-emergent Phenotypic Resistance(Up to Week 48)
- Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities Under Treatment With DTG + 3TC FDC(Up to Week 48)
- Number of Participants Who Discontinued the Study Treatment (DTG+3TC FDC) Due to AEs(Up to Week 48)
- Number of Participants With HIV-1 Disease Progression to Stage 3 HIV-associated Conditions, Acquired Immunodeficiency Syndrome (AIDS) or Death (for Participants Under Treatment With DTG + 3TC FDC)(Up to Week 48)
- Number of Participants Who Completed 24 and 48 Weeks on Study(Week 24 and Week 48)
- Number of Participants Retained in Care for 24 and 48 Weeks on Study and Have HIV-1 RNA <200 c/mL(Week 24 and Week 48)
研究者
研究点 (1)
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