A Phase IIb Randomized, Partially Blinded, Dose-Finding Trial of TMC278 in Antiretroviral-Naive HIV-1 Infected Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 368
- 主要终点
- Number of Participants With Virologic Response at Week 48 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
研究概览
简要总结
The purpose of this study is to evaluate the dose-response relationship of antiviral activity after 48 weeks treatment with 3 different dose regimens of TMC278.
详细描述
This is a randomized (the study medication is assigned by chance), active controlled (participants are assigned to either a recognized effective treatment or the study medication) study. This study consists of 3 phases: screening phase (4 weeks), treatment phase (96 weeks), and follow up phase (4 weeks). In the treatment phase, participants will be randomly assigned to 1 of the 4 treatment groups: (1) TMC278 25 mg, (2) TMC278 75 mg, (3) TMC278 150 mg, or (4) efavirnez (control group); along with investigator selected 2 non-nucleoside reverse transcriptase inhibitor (NRTIs) until Week 96. TMC278 will be assigned by double-blinded fashion (participant and investigator are not aware of the TMC278 dose what participants will receive) and efavirnez will be assigned by open-label fashion (all people know what treatment participants will receive). After Week 96, 3 optional open-label (all people know the identity of the intervention) extension periods will be conducted to collect long term safety and effectiveness data of TMC278. 3 optional extension periods are: first optional extension period (all participants will receive TMC278 75 mg + 2 NRTIs from Week 96 to Week144); second optional extension period (all participants will receive TMC278 25 mg + 2 NRTIs from Week 144 to Week 240); and third optional extension period (all participants will receive TMC278 25 mg + 2 NRTIs from Week 240 until TMC278 is commercially available). Participants on efavirenz group will have the option to continue on efavirenz + 2 NRTIs until the total treatment duration of 240 weeks. Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, physical examination, and vital signs which will be monitored throughout the study. The maximum duration of the study will be 104, 152, or 248 weeks, plus the optional third extension period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Documented human immunodeficiency virus type 1 (HIV-1) infection
- •Never been treated with an antiretroviral (ARV) treatment or therapeutic HIV vaccine, or received less than or equal to 2 weeks treatment prior to screening with an nucleoside reverse transcriptase inhibitors
- •HIV-1 plasma viral load above 5000 HIV-1 RNA copies per milliliter, at screening
- •Cortisol of at least 550 nano moles per liter (19.9 microgram per deciliter) at screening
- •Sensitivity to investigator selected nucleosides, at screening
排除标准
- •Currently having active Acquired Immunodeficiency Syndrome (AIDS) defining illness
- •Known or suspected acute (primary) HIV-1 infection
- •Any current or history of adrenal disorder, and an acute hepatitis A, B, or C infection
- •Documented genotypic evidence of Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) resistance at screening
- •Pregnant or breastfeeding females
- •Not agree to protocol-defined effective use of contraception
研究组 & 干预措施
TMC278 25 mg
Participants will receive TMC278 25 mg once daily up to Week 96. Later on, participants will receive TMC278 75 mg once daily up to Week 144 and then TMC278 25 mg once daily up to Week 240.
干预措施: TMC278 25 mg (Drug)
TMC278 25 mg
Participants will receive TMC278 25 mg once daily up to Week 96. Later on, participants will receive TMC278 75 mg once daily up to Week 144 and then TMC278 25 mg once daily up to Week 240.
干预措施: Non-nucleoside reverse transcriptase inhibitor (NRTIs) (Drug)
TMC278 75 mg
Participants will receive TMC278 75 mg once daily up to Week 144. Later on, participants will receive TMC278 25 mg once daily up to Week 240.
干预措施: TMC278 75 mg (Drug)
TMC278 75 mg
Participants will receive TMC278 75 mg once daily up to Week 144. Later on, participants will receive TMC278 25 mg once daily up to Week 240.
干预措施: Non-nucleoside reverse transcriptase inhibitor (NRTIs) (Drug)
TMC278 150 mg
Participants will receive TMC278 150 mg once daily up to Week 96. Later on, participants will receive TMC278 75 mg once daily up to Week 144 and then TMC278 25 mg once daily up to Week 240.
干预措施: TMC278 150 mg (Drug)
TMC278 150 mg
Participants will receive TMC278 150 mg once daily up to Week 96. Later on, participants will receive TMC278 75 mg once daily up to Week 144 and then TMC278 25 mg once daily up to Week 240.
干预措施: Non-nucleoside reverse transcriptase inhibitor (NRTIs) (Drug)
Efavirenz
Participants will receive efavirenz 600 mg once daily up to Week 96. Later on, participants will have an option to continue on efavirenz until Week 144 or until Week 240.
干预措施: Efavirenz (Drug)
Efavirenz
Participants will receive efavirenz 600 mg once daily up to Week 96. Later on, participants will have an option to continue on efavirenz until Week 144 or until Week 240.
干预措施: Non-nucleoside reverse transcriptase inhibitor (NRTIs) (Drug)
结局指标
主要结局
Number of Participants With Virologic Response at Week 48 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
时间窗: Week 48
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
次要结局
- Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm(Week 240)
- Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm(Week 96)
- Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis(Week 96)
- Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis(Week 240)
- Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 400 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm(Week 240)
- Change From Baseline in CD4+ Cell Count (Absolute) at Week 96(Baseline (Day 1 of Week 0) to Week 96)
- Change From Baseline in CD4+ Cell Count (Relative) at Week 96(Baseline (Day 1 of Week 0) to Week 96)
- Change From Baseline in CD4+ Cell Count (Absolute) at Week 240(Baseline (Day 1 of Week 0) to Week 240)
- Change From Baseline in CD4+ Cell Count (Relative) at Week 240(Baseline (Day 1 of week 0) to Week 240)
- Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure(Week 240)
- Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278(Up to Week 96)
- Trough Plasma Concentration (Ctrough) for TMC278(Up to Week 96)
- Number of Participants With Virologic Response (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm, by Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) Quartiles(Up to Week 96)