Clinical trial NCT04442737: A Study of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Evaluated as a Fixed Dose Combination Regimen in Participants Switching From an Integrase Inhibitor Who Have Experienced Rapid Weight Gain
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV-1
Lead sponsor: Janssen Scientific Affairs, LLC
Sponsor class: INDUSTRY
First posted: 2020-06-23
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percent Change From Baseline in Body Weight at Week 24
timeFrame: Baseline and Week 24
measure: Percent Change From Baseline in Body Weight at Week 24: Body Mass Index (BMI) >=30 Kilograms Per Square Meter (kg/m^2) Subgroup
timeFrame: Baseline and Week 24
measure: Percent Change From Baseline in Body Weight at Week 24: Female and Male Subgroup
timeFrame: Baseline and Week 24
measure: Percent Change From Baseline in Body Weight at Week 24: Black/African American and Black/African American- Female Subgroups
timeFrame: Baseline and Week 24
measure: Percent Change From Baseline in Body Weight at Week 24: Non-Black/African American Subgroup
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change From Baseline in Absolute Body Weight Over Time
timeFrame: 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
measure: Percentage of Participants With Change From Baseline Greater Than or Equal to (>=) 3% to <= 5% in Body Weight Over Time
timeFrame: 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
measure: Percentage of Participants With Change From Baseline Greater Than (>) 5 Percent (%) in Body Weight Over Time
timeFrame: 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
measure: Change From Baseline in Body Mass Index (BMI) Over Time
timeFrame: 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
measure: Change From Baseline in Body Composition as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Waist Circumference Over Time
timeFrame: 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
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
timeFrame: 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
measure: Change From Baseline in Fasting Lipids at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Fasting Glucose at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Percent of Hemoglobin A1c (HbA1c) at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Leptin at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Adiponectin at Weeks 24 and 48
timeFrame: 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
measure: Percentage of Participants With Advanced Fibrosis as Assessed by Non-alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score at Weeks 24 and 48
timeFrame: 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
measure: 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
timeFrame: 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
measure: Percentage of Participants With a Dose-reduction or Complete Withdrawal of Anti-hypertensive, Anti-hyperglycemic, or Lipid Lowering Agents
timeFrame: 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
measure: Percentage of Participants Initiating an Anti-hypertensive, Anti-hyperglycemic, or Lipid Lowering Agents
timeFrame: 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
measure: Number of Participants With Any Grade Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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
measure: Number of Participants With Grade 3 and Grade 4 TEAEs
timeFrame: 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
measure: Number of Participants Who Discontinued the Study Drug Due to TEAEs
timeFrame: 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
measure: Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: 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
measure: Change From Baseline in Biochemistry Parameters: Albumin and Protein Values at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Biochemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase Values at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Biochemistry Parameters: Bicarbonate, Calcium, Cholesterol, Chloride, Potassium, Phosphate, Sodium, Triglycerides, and Urea Nitrogen Values at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils (Segmented), Platelets, and Leukocytes Values at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Hematology Parameter: Hemoglobin Values at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Hematology Parameter: Erythrocytes Values at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Urinalysis Parameter: Specific Gravity Values at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Urinalysis Parameter: pH Values at Weeks 24 and 48
timeFrame: 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
measure: Number of Participants With Grade 3 and Grade 4 Laboratory Abnormalities
timeFrame: 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
measure: Percentage of Participants With Confirmed Virologic Rebound at Weeks 24 and 48
timeFrame: 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
measure: Percentage of Participants With Virologic Response (HIV-1 RNA<50 Copies/mL) at Weeks 24 and 48
timeFrame: 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
measure: Percentage of Participants With Virologic Failure (HIV-1 RNA >=50 Copies/mL) at Weeks 24 and 48
timeFrame: 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
measure: Percentage of Participants With Virologic Response (HIV-1 RNA<200 Copies/mL) at Weeks 24 and 48
timeFrame: 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
measure: Percentage of Participants With Virologic Failure (HIV-1 RNA >=200 Copies/mL) at Weeks 24 and 48
timeFrame: 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
measure: Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Weeks 24 and 48
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Number of Participants With Each Bothersome Symptom of the HIV-SI Adjusting for Baseline Variables at Weeks 24 and 48
timeFrame: 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
measure: Percentage of Participants With Patient Global Impression of Change (PGIC) Scale Score at Weeks 24 and 48
timeFrame: 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
measure: Adherence Rate to Treatment at Weeks 4, 12, 24, 36, and 48
timeFrame: Weeks 4, 12, 24, 36 and 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Bakersfield
country: United States
facility: The Office of Franco Felizarta, MD
state: California
city: Beverly Hills
country: United States
facility: AIDS Health Foundation-Westside HCC
state: California
city: Long Beach
country: United States
facility: Long Beach Education & Research Consultants
state: California
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute
state: Florida
city: Atlanta
country: United States
facility: Atlanta ID Group
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Macon
country: United States
facility: The Corporation of Mercer University
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department
state: Georgia
city: Chicago
country: United States
facility: The Ruth M. Rothstein CORE Center
state: Illinois
city: Baton Rouge
country: United States
facility: Care South Clinic
state: Louisiana
city: Rockville
country: United States
facility: Kaiser Permanente
state: Maryland
city: Boston
country: United States
facility: Community Research Initiative
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center, PC
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Newark
country: United States
facility: Saint Michaels Medical Center - Infectious Disease
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: AIDS Healthcare Foundation-Research Center
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital-New York
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia Fight
state: Pennsylvania
city: Columbia
country: United States
facility: Palmetto Health - USC
state: South Carolina
city: Dallas
country: United States
facility: AIDS Arms Incorporated Trinity Health and Wellness Center
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts - Donald R Watkins Foundation
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Lynchburg
country: United States
facility: Infectious Disease Associates of Central Virginia
state: Virginia
city: Milwaukee
country: United States
facility: Vivent Health
state: Wisconsin
Study officials:
affiliation: Janssen Scientific Affairs, LLC
name: Janssen Scientific Affairs, LLC Clinical Trial
role: STUDY_DIRECTOR
References: