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

NCT04442737 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: CR108757TMC114FD2HTX4004
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 34

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.

Conditions

HIV-1

Outcome Measures

Primary Outcomes (5)

• Percent Change From Baseline in Body Weight at Week 24

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

  Baseline and Week 24

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

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

  Baseline and Week 24

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

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

  Baseline and Week 24

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

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

  Baseline and Week 24

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

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

  Baseline and Week 24

Secondary Outcomes (41)

• 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

• 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

• 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 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 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

Study Arms (2)

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.

Drug: D/C/F/TAF FDC

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.

Drug: D/C/F/TAF FDC; Drug: TAF/FTC FDC; Drug: INI Based Regimen

Interventions

D/C/F/TAF FDC DRUG

A FDC tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, tenofovir alafenamide 10 mg will be administered once daily.

D/C/F/TAF FDC Arm (Immediate Switch); INI + TAF/FTC Arm (Delayed Switch)

TAF/FTC FDC DRUG

TAF/FTC ARV regimen will be administered once daily.

INI + TAF/FTC Arm (Delayed Switch)

INI Based Regimen DRUG

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.

INI + TAF/FTC Arm (Delayed Switch)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: lead

Study Sites (34)

University of Alabama at Birmingham

Birmingham, Alabama, 35222, United States

Location

The Office of Franco Felizarta, MD

Bakersfield, California, 93301, United States

Location

AIDS Health Foundation-Westside HCC

Beverly Hills, California, 90211, United States

Location

Long Beach Education & Research Consultants

Long Beach, California, 90813, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Triple O Research Institute

West Palm Beach, Florida, 33407, United States

Location

Atlanta ID Group

Atlanta, Georgia, 30309, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

The Corporation of Mercer University

Macon, Georgia, 31201, United States

Location

Chatham County Health Department

Savannah, Georgia, 31401, United States

Location

The Ruth M. Rothstein CORE Center

Chicago, Illinois, 60612, United States

Location

Care South Clinic

Baton Rouge, Louisiana, 70806, United States

Location

Kaiser Permanente

Rockville, Maryland, 20852, United States

Location

Community Research Initiative

Boston, Massachusetts, 02129, United States

Location

Be Well Medical Center, PC

Berkley, Michigan, 48072, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Washington University School Of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska

Omaha, Nebraska, 68106, United States

Location

Saint Michaels Medical Center - Infectious Disease

Newark, New Jersey, 07102, United States

Location

AIDS Healthcare Foundation-Research Center

New York, New York, 10001, United States

Location

Mount Sinai Hospital-New York

New York, New York, 10029, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Philadelphia Fight

Philadelphia, Pennsylvania, 19107, United States

Location

Palmetto Health - USC

Columbia, South Carolina, 29203, United States

Location

AIDS Arms Incorporated Trinity Health and Wellness Center

Dallas, Texas, 75208, United States

Location

North Texas Infectious Diseases Consultants

Dallas, Texas, 75246, United States

Location

Texas Centers for Infectious Disease Associates

Fort Worth, Texas, 76104, United States

Location

Therapeutic Concepts - Donald R Watkins Foundation

Houston, Texas, 77004, United States

Location

DCOL Center for Clinical Research

Longview, Texas, 75605, United States

Location

Infectious Disease Associates of Central Virginia

Lynchburg, Virginia, 24501, United States

Location

Vivent Health

Milwaukee, Wisconsin, 53203, United States

Location

Related Publications (1)

• Anderson D, Ramgopal M, Hagins DP, Lee J, Simonson RB, Hsu TH, Xu P, Ahmad N, Short WR. DEFINE: A Prospective, Randomized, Phase 4 Trial to Assess a Protease Inhibitor-Based Regimen Switch Strategy to Manage Integrase Inhibitor-Related Weight Gain. Clin Infect Dis. 2025 Mar 17;80(3):602-612. doi: 10.1093/cid/ciae449.

  PMID: 39230668 DERIVED

Results Point of Contact

• Title: Vice President Medical Affairs Infectious Disease and Vaccines (IDV)
• Organization: Janssen Scientific Affairs, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Scientific Affairs, LLC Clinical Trial

  Janssen Scientific Affairs, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 23, 2020
• Study Start: July 1, 2020
• Primary Completion: August 7, 2023
• Study Completion: August 30, 2023
• Last Updated: March 30, 2025
• Results First Posted: August 27, 2024

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (34)