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

HIV-1 Clinical Trial

— DEFINE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04442737
• Other study ID #: CR108757
• Secondary ID: TMC114FD2HTX4004
• Status: Completed
• Phase: Phase 4
• Start date: July 1, 2020
• Est. completion date: August 24, 2023

Study information

• Verified date: September 2023
• Source: Janssen Scientific Affairs, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: August 24, 2023
• Est. primary completion date: August 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV-1
• Weight Gain

Intervention

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.
• TAF/FTC FDC
TAF/FTC ARV regimen will be administered once daily.
• 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.

Locations

Country	Name	City	State
United States	Atlanta ID Group	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	The Office of Franco Felizarta, MD	Bakersfield	California
United States	Care South Clinic	Baton Rouge	Louisiana
United States	Be Well Medical Center, PC	Berkley	Michigan
United States	AIDS Health Foundation-Westside HCC	Beverly Hills	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Community Research Initiative	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	The Ruth M. Rothstein CORE Center	Chicago	Illinois
United States	Palmetto Health - USC	Columbia	South Carolina
United States	AIDS Arms Incorporated Trinity Health and Wellness Center	Dallas	Texas
United States	North Texas Infectious Diseases Consultants	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Texas Centers for Infectious Disease Associates	Fort Worth	Texas
United States	Therapeutic Concepts - Donald R Watkins Foundation	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Long Beach Education & Research Consultants	Long Beach	California
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Infectious Disease Associates of Central Virginia	Lynchburg	Virginia
United States	The Corporation of Mercer University	Macon	Georgia
United States	University of Miami	Miami	Florida
United States	Vivent Health	Milwaukee	Wisconsin
United States	AIDS Healthcare Foundation-Research Center	New York	New York
United States	Mount Sinai Hospital-New York	New York	New York
United States	Saint Michaels Medical Center - Infectious Disease	Newark	New Jersey
United States	University of Nebraska	Omaha	Nebraska
United States	Philadelphia Fight	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Kaiser Permanente	Rockville	Maryland
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Chatham County Health Department	Savannah	Georgia
United States	Triple O Research Institute	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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