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临床试验/NCT04442737
NCT04442737已完成4 期

A Phase 4, Randomized, Active-Controlled, Open-label Study to Evaluate the Safety and Tolerability of Switching to Once-Daily Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Fixed-dose Combination (FDC) Regimen in Virologically-suppressed Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Experiencing Rapid Weight Gain With an INI + TAF/FTC ARV Regimen

Janssen Scientific Affairs, LLC34 个研究点 分布在 1 个国家目标入组 103 人开始时间: 2020年7月1日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
已完成
入组人数
103
试验地点
34
主要终点
Percent Change From Baseline in Body Weight at Week 24: Black/African American and Black/African American- Female Subgroups
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to assess the percent change in body weight when switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) (Immediate Switch Arm) compared to continuing the current integrase (INI) + tenofovir alafenamide/emtricitabine (TAF/FTC) antiretroviral (ARV) regimen (Delayed Switch Arm) in virologically-suppressed human immunodeficiency virus (HIV)-1 infected participants who have experienced rapid and significant body weight gain.

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

  • •Body Mass Index (BMI) of greater than or equal to (>=) 18 kilogram per meter square (kg/m^2) at time of starting an integrase (INI)-based regimen plus Tenofovir Alafenamide/Emtricitabine (TAF/FTC) antiretroviral (ARV) regimen
  • •Documented human immunodeficiency virus (HIV)-1 infection
  • •Currently being treated with a stable ARV regimen consisting of an INI combined with TAF/FTC for >=6 consecutive months preceding the screening visit and experienced a >=10 percent (%) increase in body weight within a 36-month time period prior to screening and while on the current INI + TAF/FTC ARV regimen
  • •Documented evidence of being virologically suppressed while on the current stable INI+TAF/FTC ARV regimen prior to screening
  • •At least one plasma HIV-1 RNA measurement less than (<) 50 copies/milliliter (mL) occurring between 12 and 2 months prior to the screening visit while on the stable INI+ TAF/FTC ARV regimen and have HIV-1 RNA <50 copies/ mL at the screening visit

排除标准

  • •Known history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
  • •Known allergies, hypersensitivity, or intolerance to D/C/F/TAF fixed-dose combination (FDC) tablet or its excipients
  • •Active hepatitis B (HBV) or hepatitis C virus (HCV) infection
  • •Uncontrolled diabetes that will require treatment with insulin during the study period
  • •Evidence of Child Pugh Class C based on clinical laboratory testing and clinical evaluation
  • •History of failure on darunavir (DRV) treatment or known documented history of >=1 DRV resistance-associated mutations (RAM)
  • •Screening hepatic transaminases >5x the upper limit of the normal range
  • •Screening creatinine based estimated glomerular filtration rate (eGFRcr) <30 ml/min according to the Cockcroft-Gault formula for creatinine clearance
  • •Participants initiating or discontinuing concomitant medications associated with significant changes in weight within the last 90 days

研究组 & 干预措施

D/C/F/TAF FDC Arm (Immediate Switch)

Experimental

Participants will be immediately switched to a regimen of darunavir 800 milligram (mg)/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (D/C/F/TAF) fixed-dose combination (FDC) once daily for 48 weeks.

干预措施: D/C/F/TAF FDC (Drug)

INI + TAF/FTC Arm (Delayed Switch)

Active Comparator

Participants will continue to receive current baseline integrase (INI)-based regimen plus Tenofovir Alafenamide/Emtricitabine (TAF/FTC) antiretroviral (ARV) regimen for 24 weeks. After 24 weeks participants will switch to a regimen of D/C/F/TAF FDC once daily for an additional 24 weeks.

干预措施: D/C/F/TAF FDC (Drug)

INI + TAF/FTC Arm (Delayed Switch)

Active Comparator

Participants will continue to receive current baseline integrase (INI)-based regimen plus Tenofovir Alafenamide/Emtricitabine (TAF/FTC) antiretroviral (ARV) regimen for 24 weeks. After 24 weeks participants will switch to a regimen of D/C/F/TAF FDC once daily for an additional 24 weeks.

干预措施: TAF/FTC FDC (Drug)

INI + TAF/FTC Arm (Delayed Switch)

Active Comparator

Participants will continue to receive current baseline integrase (INI)-based regimen plus Tenofovir Alafenamide/Emtricitabine (TAF/FTC) antiretroviral (ARV) regimen for 24 weeks. After 24 weeks participants will switch to a regimen of D/C/F/TAF FDC once daily for an additional 24 weeks.

干预措施: INI Based Regimen (Drug)

结局指标

主要结局

Percent Change From Baseline in Body Weight at Week 24: Black/African American and Black/African American- Female Subgroups

时间窗: Baseline and Week 24

Percent change from baseline in body weight at Week 24 in Black/African American and Black/African American- Female subgroups were reported.

Percent Change From Baseline in Body Weight at Week 24: Non-Black/African American Subgroup

时间窗: Baseline and Week 24

Percent change from baseline in body weight at Week 24 in Non-Black/African American subgroup were reported.

Percent Change From Baseline in Body Weight at Week 24: Body Mass Index (BMI) >=30 Kilograms Per Square Meter (kg/m^2) Subgroup

时间窗: Baseline and Week 24

Percent change from baseline in body weight at Week 24 in BMI \>=30 kilograms per square meter (kg/m\^2) subgroup were reported.

Percent Change From Baseline in Body Weight at Week 24: Female and Male Subgroup

时间窗: Baseline and Week 24

Percent change from baseline in body weight at Week 24 in female and male subgroup were reported.

Percent Change From Baseline in Body Weight at Week 24

时间窗: Baseline and Week 24

Percent change from baseline in body weight at Week 24 were reported.

次要结局

  • Change From Baseline in Leptin at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Percentage of Participants at High Risk of Non-alcoholic Fatty Liver Disease (NASH) According to the Hypertension, Age, Insulin, Resistance (HAIR) Score at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Change From Baseline in Absolute Body Weight Over Time(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Baseline, Weeks 4, 12, 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 36 and 48)
  • Change From Baseline in Body Composition as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Change From Baseline in Waist Circumference Over Time(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Baseline, Weeks 4, 12, 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 36 and 48)
  • Percentage of Participants With Change From Baseline Greater Than (>) 5 Percent (%) in Body Weight Over Time(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Baseline, Weeks 4, 12, 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 36 and 48)
  • Change From Baseline in Fasting Lipids at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Percentage of Participants With Change From Baseline Greater Than or Equal to (>=) 3% to <= 5% in Body Weight Over Time(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Baseline, Weeks 4, 12, 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 36 and 48)
  • Change From Baseline in Body Mass Index (BMI) Over Time(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Baseline, Weeks 4, 12, 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 36 and 48)
  • Change From Baseline in Fasting Glucose at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Change From Baseline in Adiponectin at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Number of Participants With Grade 3 and Grade 4 TEAEs(D/C/F/TAF Immediate Switch (IS1) and INI + TAF/FTC Delayed Switch (DS1): Baseline up to Week 24; D/C/F/TAF Immediate Switch (IS2) and INI + TAF/FTC to D/C/F/TAF Delayed Switch (DS2): Week 25 up to Week 48)
  • Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Baseline, Weeks 4, 12, 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 36 and 48)
  • Change From Baseline in Percent of Hemoglobin A1c (HbA1c) at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Change From Baseline in Biochemistry Parameters: Albumin and Protein Values at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Change From Baseline in Hematology Parameter: Erythrocytes Values at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Percentage of Participants Who Had Bothersome Symptoms (Scores of 1, 2, 3 or 4) Across All Items of the HIV-Symptom Index (HIV-SI) at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Percentage of Participants Initiating an Anti-hypertensive, Anti-hyperglycemic, or Lipid Lowering Agents(D/C/F/TAF Immediate Switch (IS1) and INI + TAF/FTC Delayed Switch (DS1): Baseline up to Week 24; D/C/F/TAF Immediate Switch (IS2) and INI + TAF/FTC to D/C/F/TAF Delayed Switch (DS2): Week 25 up to Week 48)
  • Number of Participants Who Discontinued the Study Drug Due to TEAEs(D/C/F/TAF Immediate Switch (IS1) and INI + TAF/FTC Delayed Switch (DS1): Baseline up to Week 24; D/C/F/TAF Immediate Switch (IS2) and INI + TAF/FTC to D/C/F/TAF Delayed Switch (DS2): Week 25 up to Week 48)
  • Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils (Segmented), Platelets, and Leukocytes Values at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Change From Baseline in Urinalysis Parameter: pH Values at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Percentage of Participants With Virologic Response (HIV-1 RNA<200 Copies/mL) at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Week 24; D/C/F/TAF Immediate Switch (IS): Week 48)
  • Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Percentage of Participants Who Had Any Symptoms (Scores of 1, 2, 3 or 4) Across All Items of the HIV-Symptom Index (HIV-SI) at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Percentage of Participants With Patient Global Impression of Change (PGIC) Scale Score at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Week 24; D/C/F/TAF Immediate Switch (IS): Week 48)
  • Percentage of Participants With Advanced Fibrosis as Assessed by Non-alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Week 24; D/C/F/TAF Immediate Switch (IS): Week 48)
  • Percentage of Participants With a Dose-reduction or Complete Withdrawal of Anti-hypertensive, Anti-hyperglycemic, or Lipid Lowering Agents(D/C/F/TAF Immediate Switch (IS1) and INI + TAF/FTC Delayed Switch (DS1): Baseline up to Week 24; D/C/F/TAF Immediate Switch (IS2) and INI + TAF/FTC to D/C/F/TAF Delayed Switch (DS2): Week 25 up to Week 48)
  • Change From Baseline in Biochemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase Values at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Change From Baseline in Biochemistry Parameters: Bicarbonate, Calcium, Cholesterol, Chloride, Potassium, Phosphate, Sodium, Triglycerides, and Urea Nitrogen Values at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Percentage of Participants With Virologic Failure (HIV-1 RNA >=200 Copies/mL) at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Week 24; D/C/F/TAF Immediate Switch (IS): Week 48)
  • Number of Participants With Any Grade Treatment-emergent Adverse Events (TEAEs)(D/C/F/TAF Immediate Switch (IS1) and INI + TAF/FTC Delayed Switch (DS1): Baseline up to Week 24; D/C/F/TAF Immediate Switch (IS2) and INI + TAF/FTC to D/C/F/TAF Delayed Switch (DS2): Week 25 up to Week 48)
  • Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)(D/C/F/TAF Immediate Switch (IS1) and INI + TAF/FTC Delayed Switch (DS1): Baseline up to Week 24; D/C/F/TAF Immediate Switch (IS2) and INI + TAF/FTC to D/C/F/TAF Delayed Switch (DS2): Week 25 up to Week 48)
  • Change From Baseline in Urinalysis Parameter: Specific Gravity Values at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Number of Participants With Grade 3 and Grade 4 Laboratory Abnormalities(D/C/F/TAF Immediate Switch (IS1) and INI + TAF/FTC Delayed Switch (DS1): Baseline up to Week 24; D/C/F/TAF Immediate Switch (IS2) and INI + TAF/FTC to D/C/F/TAF Delayed Switch (DS2): Week 25 up to Week 48)
  • Adherence Rate to Treatment at Weeks 4, 12, 24, 36, and 48(Weeks 4, 12, 24, 36 and 48)
  • Change From Baseline in Hematology Parameter: Hemoglobin Values at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS1): Baseline, Week 24; D/C/F/TAF Immediate Switch (IS): Baseline, Week 48)
  • Percentage of Participants With Confirmed Virologic Rebound at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Week 24; D/C/F/TAF Immediate Switch (IS): Week 48)
  • Percentage of Participants With Virologic Response (HIV-1 RNA<50 Copies/mL) at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Week 24; D/C/F/TAF Immediate Switch (IS): Week 48)
  • Percentage of Participants With Virologic Failure (HIV-1 RNA >=50 Copies/mL) at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Week 24; D/C/F/TAF Immediate Switch (IS): Week 48)
  • Number of Participants With Each Bothersome Symptom of the HIV-SI Adjusting for Baseline Variables at Weeks 24 and 48(INI + TAF/FTC Delayed Switch (DS1) and D/C/F/TAF Immediate Switch (IS1): Week 24; D/C/F/TAF Immediate Switch (IS): Week 48)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (34)

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