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

NCT ID: NCT04442737

Last Updated: 2025-03-30

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

103 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-01

Study Completion Date

2023-08-30

Brief Summary

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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.

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Detailed Description

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Conditions

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HIV-1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

D/C/F/TAF FDC

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

D/C/F/TAF FDC

Intervention Type DRUG

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

TAF/FTC FDC

Intervention Type DRUG

TAF/FTC ARV regimen will be administered once daily.

INI Based Regimen

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

TAF/FTC FDC

TAF/FTC ARV regimen will be administered once daily.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Scientific Affairs, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Scientific Affairs, LLC

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

The Office of Franco Felizarta, MD

Bakersfield, California, United States

Site Status

AIDS Health Foundation-Westside HCC

Beverly Hills, California, United States

Site Status

Long Beach Education & Research Consultants

Long Beach, California, United States

Site Status

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Triple O Research Institute

West Palm Beach, Florida, United States

Site Status

Atlanta ID Group

Atlanta, Georgia, United States

Site Status

Medical College of Georgia

Augusta, Georgia, United States

Site Status

The Corporation of Mercer University

Macon, Georgia, United States

Site Status

Chatham County Health Department

Savannah, Georgia, United States

Site Status

The Ruth M. Rothstein CORE Center

Chicago, Illinois, United States

Site Status

Care South Clinic

Baton Rouge, Louisiana, United States

Site Status

Kaiser Permanente

Rockville, Maryland, United States

Site Status

Community Research Initiative

Boston, Massachusetts, United States

Site Status

Be Well Medical Center, PC

Berkley, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Washington University School Of Medicine

St Louis, Missouri, United States

Site Status

University of Nebraska

Omaha, Nebraska, United States

Site Status

Saint Michaels Medical Center - Infectious Disease

Newark, New Jersey, United States

Site Status

AIDS Healthcare Foundation-Research Center

New York, New York, United States

Site Status

Mount Sinai Hospital-New York

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Philadelphia Fight

Philadelphia, Pennsylvania, United States

Site Status

Palmetto Health - USC

Columbia, South Carolina, United States

Site Status

AIDS Arms Incorporated Trinity Health and Wellness Center

Dallas, Texas, United States

Site Status

North Texas Infectious Diseases Consultants

Dallas, Texas, United States

Site Status

Texas Centers for Infectious Disease Associates

Fort Worth, Texas, United States

Site Status

Therapeutic Concepts - Donald R Watkins Foundation

Houston, Texas, United States

Site Status

DCOL Center for Clinical Research

Longview, Texas, United States

Site Status

Infectious Disease Associates of Central Virginia

Lynchburg, Virginia, United States

Site Status

Vivent Health

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 39230668 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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TMC114FD2HTX4004

Identifier Type: OTHER

Identifier Source: secondary_id

CR108757

Identifier Type: -

Identifier Source: org_study_id

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