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)

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 4

Conditions: HIV-1

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04442737

CR108757

TMC114FD2HTX4004 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 103 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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103 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: D/C/F/TAF FDC

INI + TAF/FTC Arm (Delayed Switch)

Active Comparator group

Description:

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.

Treatment:

Drug: TAF/FTC FDC

Drug: D/C/F/TAF FDC

Drug: INI Based Regimen