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 (DEFINE)

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1
• Intervention / Treatment: Drug: D/C/F/TAF FDC; Drug: TAF/FTC FDC; Drug: INI Based Regimen

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35222
      • University of Alabama At Birmingham
  • California
    • Bakersfield, California, United States, 93301
      • The Office of Franco Felizarta, MD
    • Beverly Hills, California, United States, 90211
      • AIDS Health Foundation-Westside HCC
    • Long Beach, California, United States, 90813
      • Long Beach Education & Research Consultants
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami, Florida, United States, 33136
      • University of Miami
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
    • Macon, Georgia, United States, 31201
      • The Corporation of Mercer University
    • Savannah, Georgia, United States, 31401
      • Chatham County Health Department
  • Illinois
    • Chicago, Illinois, United States, 60612
      • The Ruth M. Rothstein CORE Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70806
      • Care South Clinic
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Kaiser Permanente
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Community Research Initiative
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center, PC
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • University of Nebraska
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michaels Medical Center - Infectious Disease
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10001
      • AIDS Healthcare Foundation-Research Center
    • New York, New York, United States, 10029
      • Mount Sinai Hospital-New York
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Palmetto Health - USC
  • Texas
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants
    • Dallas, Texas, United States, 75208
      • AIDS Arms Incorporated Trinity Health and Wellness Center
    • Fort Worth, Texas, United States, 76104
      • Texas Centers for Infectious Disease Associates
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts - Donald R Watkins Foundation
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Infectious Disease Associates of Central Virginia
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53203
      • Vivent Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D/C/F/TAF FDC Arm (Immediate Switch); 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.	Drug: D/C/F/TAF FDC; A FDC tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, tenofovir alafenamide 10 mg will be administered once daily.
Active Comparator: INI + TAF/FTC Arm (Delayed Switch); 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.	Drug: D/C/F/TAF FDC; A FDC tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, tenofovir alafenamide 10 mg will be administered once daily.; Drug: TAF/FTC FDC; TAF/FTC ARV regimen will be administered once daily.; Drug: INI Based Regimen; The integrase (INI) inhibitors (for example, bictegravir, dolutegravir, elvitegravir/cobicistat, and raltegravir) will be administered in combination with TAF/FTC, as appropriate. Regimen may consist of a single tablet regimen or a combination of two separate pills.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change from Baseline in Body Weight at Week 24	Percent change from baseline in body weight at Week 24 will be reported.	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Absolute Body Weight at Weeks 24 and 48	Change from baseline in absolute body weight at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Percentage of Participants with Percent Change in Body Weight Greater Than (>) 3 Percent (%) at Weeks 24 and 48	Percentage of participants with % change in body weight >3% at Weeks 24 and 48 will be reported.	Weeks 24 and 48
Percentage of Participants with Percent Change in Body Weight >5% at Weeks 24 and 48	Percentage of participants with % change in body weight >5% at Weeks 24 and 48 will be reported.	Weeks 24 and 48
Change from Baseline in Body Mass Index (BMI) at Weeks 24 and 48	Change from baseline in BMI at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Body Composition as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at Weeks 24 and 48	Change from baseline in body composition (absolute mass of fat, lean body mass and total mass) as measured by DEXA scan at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Waist Circumference at Weeks 24 and 48	Change from baseline in waist circumference at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 24 and 48	Change from baseline in SBP and DBP from Baseline at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Fasting Lipids at Weeks 24 and 48	Change from baseline in fasting lipids at Weeks 24 and 48 will be reported. Fasting plasma lipids are measured to determine triglyceride or cholesterol concentrations.	Baseline, Weeks 24 and 48
Change from Baseline in Fasting Glucose at Weeks 24 and 48	Change from baseline in fasting glucose at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Weeks 24 and 48	Change from baseline in HOMA-IR at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Hemoglobin A1c (HbA1c) at Weeks 24 and 48	Change from baseline in HbA1c at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Leptin at Weeks 24 and 48	Change from baseline in leptin at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Adiponectin at Weeks 24 and 48	Change from baseline in adiponectin at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in the Percentage of Participants with Advanced Fibrosis as Assessed by Non-alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score at Weeks 24 and 48	Change from baseline in the percentage of participants with advanced fibrosis according to the NAFLD fibrosis score at Weeks 24 and 48 will be reported. In participants with NAFLD Score less than (< ) -1.455, advanced liver fibrosis can be excluded with high accuracy and NAFLD Score greater than (>) 0.675, the presence of advanced liver fibrosis can be diagnosed with high accuracy. Scores between -1.455 and 0.675 are considered "indeterminate".	Baseline, Weeks 24 and 48
Change from Baseline in the Percentage of Participants at High Risk of Nonalcoholic Fatty Liver Disease (NASH) According to the Hypertension, Age, Insulin, Resistance (HAIR) Score at Weeks 24 and 48	Change from baseline in the percentage of participants at high risk of NASH according to the HAIR score at Weeks 24 and 48 will be reported. HAIR score ranges from 0-3 which is calculated by adding Hypertension = 1, ALT >40 IU=1, and insulin resistance (IR) index >5.0 = 1. A score of greater than or equal to (>=) 2 is high risk for NASH.	Baseline, Weeks 24 and 48
Percentage of Participants with a Dose-reduction or Complete Withdrawal of Anti-hypertensive, Anti-hyperglycemic, or Lipid Lowering Agents	Percentage of participants with a dose-reduction or complete withdrawal of anti-hypertensive, anti-hyperglycemic, or lipid lowering agents from baseline to Weeks 24 and 48 will be reported.	Baseline up to Weeks 24 and 48
Percentage of Participants Initiating an Anti-hypertensive, Anti-hyperglycemic, or Lipid Lowering Agent	Percentage of participants initiating an anti-hypertensive, anti-hyperglycemic, or lipid lowering agent from baseline to Weeks 24 and 48 will be reported.	Baseline up to Weeks 24 and 48
Percentage of Participants with any Grade Adverse Events (AEs)	Percentage of participants with any Grade AEs (related and not related) will be reported.	Up to 24 and 48 weeks
Percentage of Participants with Grade 3 and Grade 4 AEs	Percentage of participants with Grade 3 and Grade 4 AEs (related and not related) will be reported where Grade 3: Severe and Grade 4: Potentially life-threatening.	Up to 24 and 48 weeks
Percentage of Participants who Discontinued due to AEs	Percentage of participants who discontinued due to AEs will be reported.	Up to 24 and 48 weeks
Percentage of Participants with Serious Adverse Events (SAEs)	Percentage of participants with SAEs (related and not related) through Week 24 and Week 48 will be reported.	Up to 24 and 48 weeks
Change from Baseline in Biochemistry Tests	Change from baseline in biochemistry tests (such as sodium, potassium, chloride, bicarbonate, blood urea nitrogen, serum creatinine, glucose, aspartate aminotransferase, alanine aminotransferase, insulin, bilirubin [total, direct, indirect], alkaline phosphatase, calcium, calcium corrected for albumin, phosphate, albumin, total protein) through Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Hematology Tests	Change from baseline in hematology tests (hematocrit, hemoglobin, platelet count, red blood cell count, absolute neutrophil count, white blood cell count) through Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Urinalysis Tests	Change from baseline in urinalysis tests (specific gravity, pH, glucose, protein, blood ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase) through Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Change from Baseline in Urine Chemistry Tests	If applicable, change from baseline in urine chemistry tests (urine creatinine, urine sodium, urine phosphate, urine glucose, urine albumin, urine protein, serum creatinine) through Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Percentage of Participants with Grade 3 and Grade 4 Laboratory Abnormalities	Percentage of participants with Grade 3 and Grade 4 laboratory abnormalities will be reported.	Up to 24 and 48 weeks
Percentage of Participants with Confirmed Virologic Rebound	Percentage of participants with confirmed virologic rebound through Weeks 24 and 48 will be reported. Virologic rebound is defined as the 2 consecutive human immunodeficiency virus type-1 ribonucleic acid (HIV-1 RNA) values greater than or equal to (>=) 200 copies/milliliter (mL) at a scheduled or unscheduled visit after maintaining HIV-1 RNA less than (<) 50 copies/mL.	Up to Weeks 24 and 48
Percentage of Participants with Virologic Response (HIV-1 RNA<50 copies/mL) at Weeks 24 and 48	Percentage of participants with virologic response (HIV-1 RNA <50 copies/mL), at Weeks 24 and 48 according to the Food Drug Administration (FDA) snapshot algorithm will be reported.	Weeks 24 and 48
Percentage of Participants with Virologic Failure (HIV-1 RNA ≥50 copies/mL) at Weeks 24 and 48	Percentage participants with virologic failure (HIV-1 RNA >=50 copies/mL) at Weeks 24 and 48 according to the FDA snapshot algorithm will be reported.	Weeks 24 and 48
Percentage of Participants Having Virologic Response (HIV-1 RNA<200 copies/mL) at Weeks 24 and 48	Percentage participants with virologic response (HIV-1 RNA < 200 copies/mL) at Weeks 24 and 48 according to the FDA snapshot algorithm will be reported.	Weeks 24 and 48
Percentage of Participants Having Virologic Failure (HIV-1 RNA ≥200 copies/mL) at Weeks 24 and 48	Percentage participants having virologic failure, that is HIV-1 RNA >= 200 copies/mL, at Weeks 24 and 48 according to the FDA snapshot algorithm will be reported.	Weeks 24 and 48
Change from Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Weeks 24 and 48	Change from baseline in CD4+ cell count at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Percentage of Participants with Pre-baseline Protease (PR), Reverse Transcriptase (RT), and Integrase (INI) Resistance-Associated Mutation (RAMs)	Percentage of participants with pre-baseline PR, RT, and INI RAMs based on historical genotypes will be reported.	Baseline (Day 1)
Percentage of Participant with Newly Identified Post-Baseline RAMS and Phenotypic Resistance Compared to Pre-baseline Resistance Tests	Percentage of participant with newly identified post-baseline RAMs and phenotypic resistance compared to pre-baseline resistance tests when available, upon meeting confirmed virologic rebound through Week 48.	Up to Week 48
Percentage of Participants with Genotypic and Phenotypic Antiretroviral (ARV) Resistance for Meeting HIV-1 RNA Rebound Criteria up to Weeks 24 and 48	Percentage of participants with genotypic and phenotypic ARV resistance who are meeting HIV-1 RNA rebound criteria through Weeks 24 and 48 will be reported.	Up to Weeks 24 and 48
Change from Baseline in the Percentage of Participants who Have Bothersome Symptoms (Scores of 1, 2, 3 or 4) Across all Items of the HIV-Symptom Index (HIV-SI) at Weeks 24 and 48	Change from baseline in the percentage of participants who have bothersome symptoms (scores of 1, 2, 3 or 4) across all items of the HIV-SI at Weeks 24 and 48 will be reported. The HIV-SI assesses 20 items which are evaluated on a scale of 0-4 where 0= I do not have this symptom to 4=It bothers me a lot'. Minimum HIV-SI score is 0 and maximum HIV-SI score is 80.	Baseline, Weeks 24 and 48
Change from Baseline in the Percentage of Participants who Have Any Symptoms (scores of 1, 2, 3 or 4) Across all Items of the HIV-Symptom Index (HIV-SI) at Weeks 24 and 48	Change from baseline in the percentage of participants who have any symptoms (scores of 1, 2, 3 or 4) across all items of the HIV-SI at Weeks 24 and 48 will be reported.	Baseline, Weeks 24 and 48
Association Between Treatment Arm and Each Bothersome Symptom of the HIV-SI Adjusting for Baseline Variables at Week 24	Association between treatment arm and each bothersome symptom of the HIV-SI adjusting for Baseline variables at Week 24 will be reported.	Week 24
Patient Global Impression of Change (PGIC) Scale	The PGIC is a global index that is used to rate the overall status of the participant related to the participant's overall condition. It is rated by the participant and is based on the single question, "compared to before starting the study or compared to the Week 24 and Week 48 visits, my overall status is," where response choices include 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse.	Weeks 24 and 48
Adherence Rate to Treatment at Weeks 4, 12 and 24	Adherence rate to treatment will be assessed by participant self-report using 4-day recall at Weeks 4, 12, 24, 36 and 48.	Weeks 4, 12, 24, 36 and 48

Collaborators and Investigators

• Sponsor: Janssen Scientific Affairs, LLC
• Investigators: Study Director: Janssen Scientific Affairs, LLC Clinical Trial, Janssen Scientific Affairs, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): August 7, 2023
• Study Completion (Actual): August 24, 2023

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 23, 2020

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Gain
• Other Study ID Numbers: CR108757; TMC114FD2HTX4004 (Other Identifier: Janssen Scientific Affairs, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No