Phase 4
N=103
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
Bottom Line
View on ClinicalTrials.gov: NCT04442737 ↗Enrolled (actual)
103
Serious AEs
6.6%
Results posted
Aug 2024
Primary outcome: Primary: Percent Change From Baseline in Body Weight at Week 24 — 0.63; -0.24 Percent Change
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- D/C/F/TAF FDC (Drug); TAF/FTC FDC (Drug); INI Based Regimen (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Janssen Scientific Affairs, LLC
- Primary completion
- Aug 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Body Weight at Week 24 |
0.63; -0.24 | — |
| PRIMARY Percent Change From Baseline in Body Weight at Week 24: Body Mass Index (BMI) >=30 Kilograms Per Square Meter (kg/m^2) Subgroup |
0.26; 0.18 | — |
| PRIMARY Percent Change From Baseline in Body Weight at Week 24: Female and Male Subgroup |
1.26; -0.89; 0.46; -0.22 | — |
| PRIMARY Percent Change From Baseline in Body Weight at Week 24: Black/African American and Black/African American- Female Subgroups |
0.50; -1.36; 0.62; -0.82 | — |
| PRIMARY Percent Change From Baseline in Body Weight at Week 24: Non-Black/African American Subgroup |
1.00; 1.14 | — |
| SECONDARY Change From Baseline in Absolute Body Weight Over Time |
-0.20; -0.20; 0.10; 0.20; 0.30; 0.50 | — |
| SECONDARY Percentage of Participants With Change From Baseline Greater Than or Equal to (>=) 3% to <= 5% in Body Weight Over Time |
2.0; 3.8; 4.1; 7.5; 8.9; 5.8 | — |
| SECONDARY Percentage of Participants With Change From Baseline Greater Than (>) 5 Percent (%) in Body Weight Over Time |
4.1; 0; 2.0; 0; 6.7; 3.8 | — |
| SECONDARY Change From Baseline in Body Mass Index (BMI) Over Time |
-0.06; -0.07; 0.03; 0.07; 0.10; 0.20 | — |
| SECONDARY Change From Baseline in Body Composition as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at Weeks 24 and 48 |
-0.59; 0.12; -1.24; -0.51; 0.22; -0.29 | — |
| SECONDARY Change From Baseline in Waist Circumference Over Time |
0.00; 0.00; 0.20; 0.00; 0.00; 0.80 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time |
3.0; -2.0; 0.0; 1.0; 0.5; -3.0 | — |
| SECONDARY Change From Baseline in Fasting Lipids at Weeks 24 and 48 |
0.11; 0.86; 0.73; -0.13; 0.04; 0.05 | — |
| SECONDARY Change From Baseline in Fasting Glucose at Weeks 24 and 48 |
0.05; -0.08; 0.06 | — |
| SECONDARY Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Weeks 24 and 48 |
-0.81; -0.05; 0.01 | — |
| SECONDARY Change From Baseline in Percent of Hemoglobin A1c (HbA1c) at Weeks 24 and 48 |
0.01; -0.07; -0.10 | — |
| SECONDARY Change From Baseline in Leptin at Weeks 24 and 48 |
-6.85; -1.09; 4.11 | — |
| SECONDARY Change From Baseline in Adiponectin at Weeks 24 and 48 |
-0.16; -0.11; 0.05 | — |
| SECONDARY Percentage of Participants With Advanced Fibrosis as Assessed by Non-alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score at Weeks 24 and 48 |
44.0; 50.9; 54.7; 5.7; 12.0; 9.4 | — |
| SECONDARY Percentage of Participants at High Risk of Non-alcoholic Fatty Liver Disease (NASH) According to the Hypertension, Age, Insulin, Resistance (HAIR) Score at Weeks 24 and 48 |
62.0; 60.4; 56.6; 12.0; 3.8; 5.7 | — |
| SECONDARY Percentage of Participants With a Dose-reduction or Complete Withdrawal of Anti-hypertensive, Anti-hyperglycemic, or Lipid Lowering Agents |
0; 0; 0; 0; 0; 0. | — |
| SECONDARY Percentage of Participants Initiating an Anti-hypertensive, Anti-hyperglycemic, or Lipid Lowering Agents |
7.5; 5.7; 18.0; 12.0; 0; 0. | — |
| SECONDARY Number of Participants With Any Grade Treatment-emergent Adverse Events (TEAEs) |
30; 29; 26; 30 | — |
| SECONDARY Number of Participants With Grade 3 and Grade 4 TEAEs |
3; 3; 3; 5; 0; 1 | — |
| SECONDARY Number of Participants Who Discontinued the Study Drug Due to TEAEs |
0; 3; 0; 2 | — |
| SECONDARY Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) |
4; 3; 2; 4 | — |
| SECONDARY Change From Baseline in Biochemistry Parameters: Albumin and Protein Values at Weeks 24 and 48 |
0.1; 0.4; 0.1; -0.4; 1.8; 0.6 | — |
| SECONDARY Change From Baseline in Biochemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase Values at Weeks 24 and 48 |
8.50; 0.0; -2.8; -4.2; -3.7; -0.1 | — |
| SECONDARY Change From Baseline in Biochemistry Parameters: Bicarbonate, Calcium, Cholesterol, Chloride, Potassium, Phosphate, Sodium, Triglycerides, and Urea Nitrogen Values at Weeks 24 and 48 |
0.70; 0.09; 0.52; 0.00; 0.02; -0.02 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils (Segmented), Platelets, and Leukocytes Values at Weeks 24 and 48 |
0.00; 0.00; -0.01; -0.01; -0.01; -0.02 | — |
| SECONDARY Change From Baseline in Hematology Parameter: Hemoglobin Values at Weeks 24 and 48 |
-0.1; -1.2; -2.7 | — |
| SECONDARY Change From Baseline in Hematology Parameter: Erythrocytes Values at Weeks 24 and 48 |
0.05; -0.06; -0.09 | — |
| SECONDARY Change From Baseline in Urinalysis Parameter: Specific Gravity Values at Weeks 24 and 48 |
0.00; 0.00; 0.00 | — |
| SECONDARY Change From Baseline in Urinalysis Parameter: pH Values at Weeks 24 and 48 |
0.00; -0.07; -0.06 | — |
| SECONDARY Number of Participants With Grade 3 and Grade 4 Laboratory Abnormalities |
1; 2; 1; 1 | — |
| SECONDARY Percentage of Participants With Confirmed Virologic Rebound at Weeks 24 and 48 |
4.0; 0; 0 | — |
| SECONDARY Percentage of Participants With Virologic Response (HIV-1 RNA<50 Copies/mL) at Weeks 24 and 48 |
80.0; 90.6; 81.1 | — |
| SECONDARY Percentage of Participants With Virologic Failure (HIV-1 RNA >=50 Copies/mL) at Weeks 24 and 48 |
10.0; 0; 3.8 | — |
| SECONDARY Percentage of Participants With Virologic Response (HIV-1 RNA<200 Copies/mL) at Weeks 24 and 48 |
86.0; 90.6; 84.9 | — |
| SECONDARY Percentage of Participants With Virologic Failure (HIV-1 RNA >=200 Copies/mL) at Weeks 24 and 48 |
4.0; 0; 0 | — |
| SECONDARY Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Weeks 24 and 48 |
9.0; 61.0; -41.0 | — |
| SECONDARY Percentage of Participants Who Had Bothersome Symptoms (Scores of 1, 2, 3 or 4) Across All Items of the HIV-Symptom Index (HIV-SI) at Weeks 24 and 48 |
61.2; 43.5; 54.5; 47.7; 42.9; 26.5 | — |
| SECONDARY Percentage of Participants Who Had Any Symptoms (Scores of 1, 2, 3 or 4) Across All Items of the HIV-Symptom Index (HIV-SI) at Weeks 24 and 48 |
73.5; 45.7; 61.4; 59.1; 47.6; 34.7 | — |
| SECONDARY Number of Participants With Each Bothersome Symptom of the HIV-SI Adjusting for Baseline Variables at Weeks 24 and 48 |
44; 44; 42 | — |
| SECONDARY Percentage of Participants With Patient Global Impression of Change (PGIC) Scale Score at Weeks 24 and 48 |
11.4; 4.9; 13.6; 22.0; 18.2; 19.5 | — |
| SECONDARY Adherence Rate to Treatment at Weeks 4, 12, 24, 36, and 48 |
92.9; 90.6; 7.1; 9.4; 0; 0 | — |
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.
Eligibility Criteria
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 ( =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
Data sourced from ClinicalTrials.gov (NCT04442737). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.