A Study to Evaluate the Efficacy and Safety of (D/C/F/TAF) Once Daily Fixed Dose Combination (FDC) Regimen in Newly Diagnosed, Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Receiving Care in a Test and Treat Model of Care

HIV-1 Clinical Trial

Official title:

A Phase 3, Single-arm, Open-label Study to Evaluate the Efficacy and Safety of Darunavir/ Cobicistat/ Emtricitabine/ Tenofovir Alafenamide (D/C/F/TAF) Once Daily Fixed-dose Combination (FDC) Regimen in Newly Diagnosed, Antiretroviral Treatment-naïve Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects Receiving Care in a Test and Treat Model of Care

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03227861
• Other study ID #: CR108345
• Secondary ID: TMC114FD2HTX3002
• Status: Completed
• Phase: Phase 3
• Start date: July 31, 2017
• Est. completion date: September 4, 2019

Study information

• Verified date: September 2020
• 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 efficacy of Darunavir/ Cobicistat/ Emtricitabine/ Tenofovir Alafenamide (D/C/F/TAF) fixed-dose combination (FDC) in a Test and Treat model of care in newly diagnosed human immunodeficiency virus (HIV-1)-infected, treatment-naive participants as determined by the proportion of virologic responders defined as having (HIV)-1 ribonucleic acid (RNA) lesser than 50 copies per milliliter (copies/mL) at Week 48.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: September 4, 2019
• Est. primary completion date: January 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Newly diagnosed with human immunodeficiency virus type 1 (HIV-1) evidenced by any of the following within 2 weeks of the screening/baseline visit: a) HIV Rapid Antibody positive; or b) HIV Immunoassay positive; or c) Positive p24 antigen and a HIV-1 ribonucleic acid (RNA) viral load greater than or equal to (>=) 5,000 copies per milliliter (copies/ mL); or d) Non-reactive HIV-1 antibody/antigen assays and HIV-1 RNA viral load (>=) 5,000 copies/mL. HIV-1 RNA viral load must be confirmed once within 1 week of initial HIV-1 RNA viral load test

• Antiretroviral treatment-naïve, except for the use of TRUVADA® for pre-exposure prophylaxis (PrEP)

• Must be able to swallow whole tablets

• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 90 days after receiving the last dose of study drug

• A woman of childbearing potential must have a negative urine pregnancy test at screening

Exclusion Criteria:

• Known active cryptococcal infection, active toxoplasmic encephalitis, Mycobacterium tuberculosis infection, or another acquired immunodeficiency syndrome (AIDS) -defining condition that in the judgement of the investigator would increase the risk of morbidity or mortality

• Known history of clinically relevant hepatic disease or hepatitis that in the investigator's judgement is not compatible with Darunavir/ Cobicistat/ Emtricitabine/ Tenofovir Alafenamide (D/C/F/TAF FDC)

• Known history of cirrhosis as diagnosed based on local practices

• Known history of chronic ([>=] 3 months) renal insufficiency, defined as having an estimated glomerular filtration rate (eGFR) less than (<) 50 milliliter per minute (mL/min) according to the Modification of Diet in Renal Disease (MDRD) formula

• Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• HIV-1

Intervention

Drug:
• DRV 800 mg + COBI 150 mg + FTC 200 mg + TAF 10 mg FDC
Participants will receive oral tablet containing D 800 mg /C 150 mg /F 200 mg /TAF 10 mg FDC once daily within 24 hours of the screening/ baseline visit.

Locations

Country	Name	City	State
United States	Southwest CARE Center	Albuquerque	New Mexico
United States	The Office of Franco Felizarta, MD	Bakersfield	California
United States	The Ruth M. Rothstein CORE Center	Chicago	Illinois
United States	North Texas Infectious Diseases Consultants	Dallas	Texas
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Texas Centers for Infectious Disease Associates	Fort Worth	Texas
United States	Gordon Crofoot, MD	Houston	Texas
United States	Therapeutic Concepts - Donald R Watkins Foundation	Houston	Texas
United States	Jeffrey Goodman Clinic - DBA Los Angeles Gay and Lesbian Center	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Saint Michael's Medical Center - Infectious Disease	Newark	New Jersey
United States	Orlando Immunology Center	Orlando	Florida
United States	Spectrum Medical Group	Phoenix	Arizona
United States	Southwest CARE Center	Santa Fe	New Mexico
United States	Chatham County Health Department	Savannah	Georgia
United States	Whitman Walker Health	Washington	District of Columbia

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	Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies/mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach	Percentage of participants with a HIV-1 RNA < 50 copies per mL were assessed using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within a window of time, along with study drug discontinuation status. If HIV RNA level is < 50 copies per mL at Week 48, it is considered as virologic success as per the snapshot approach.	Week 48
Secondary	Change From Baseline in log10 HIV-1 RNA Viral Load (<50/200 Copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48	Change from baseline in log10 HIV-1 RNA viral load (<50/200 copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 were reported.	Baseline, Weeks 2, 4, 8, 12, 24, 36, and 48
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24	Percentage of participants with HIV-1 RNA < 50 copies/mL were reported.	Week 24
Secondary	Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 12, 24 and 48	The immunologic change was determined by changes in Cluster of CD4+ cell count. Change from baseline in CD4+ cell count at Weeks 12, 24 and 48 were assessed.	Baseline, Weeks 12, 24 and 48
Secondary	Number of Participants That Required Discontinuation After Enrollment Based on Safety Stopping Rules	Number of participants that required discontinuation after enrollment based on safety stopping rules were reported. Stopping rules include the following reasons: a). Estimated glomerular filtration rate (eGFR) according to the Modification of Diet in Renal Disease (MDRD) formula < 50 milliliter per minute (mL/min) b). Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal to (>=) 2.5*upper limit of normal (ULN); c). Serum lipase >=1.5*ULN; d). Positive serum human chorionic gonadotropin pregnancy test (beta-hCG) for women of childbearing potential; e). Laboratory results that the investigator believes should result in discontinuation of study medication; f). Participants identified with active hepatitis C virus (HCV) infection that in the opinion of the investigator requires HCV treatment immediately or expected to be needed during the course of the study with agents not compatible with D/C/F/TAF FDC.	Up to Week 48
Secondary	Percentage of Participants Discontinuing Therapy Due to Adverse Events (AEs)	Percentage of participants discontinuing therapy due to AEs were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Up to Week 48
Secondary	Percentage of Participants Experiencing Grade 3 and 4 Adverse Events	AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events.	Up to Week 48
Secondary	Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities	Percentage of participants experiencing grade 3 and 4 laboratory abnormalities was assessed by Division of Acquired Immunodeficiency Syndrome (DAIDS) Adverse Event (AE) Grading Table. Abnormal laboratory values with Grade 3 or higher (3=Severe; 4=potentially life-threatening) signifies an interruption of usual daily activity, requiring systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable.	Up to Week 48
Secondary	Percentage of Participants Meeting Resistance Stopping Rules, Requiring Discontinuation of Study Treatment Due to Baseline Resistance Findings	Percentage of participants meeting resistance stopping rules, requiring discontinuation of study treatment due to baseline resistance findings were reported. Investigator reviewed antiretroviral screening/baseline resistance data at Week 4, depending on availability of screening/baseline HIV genotypic drug resistance testing results from central laboratory. Participants who do not show full sensitivity to all drugs in the fixed-dose combination (FDC) study regimen according to the susceptibility assessment in the Genosure Prime report will be contacted to return to study site for early study treatment discontinuation (ESTD). Participants with identified resistance to lamivudine/Emtricitabine, attributed to the presence of the M184I/V mutation alone will be permitted to remain in the study.	Up to Day 35
Secondary	Percentage of Participants With Baseline Protease (PI), Reverse Transcriptase (RT) and Integrase (INI)-Resistance-associated Mutation (RAMs)	Percentage of Participants with resistance-associated mutations present at baseline were reported and included mutations in the domain of PR, RT (including nucleoside reverse transcriptase inhibitor [NRTIs] and non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTIs]), INI, RAMs as determined by the GenoSure Prime assay. Genotypes were not available for 7 participants due to failed amplification of viral deoxyribo nucleic acid (DNA) (that is, low viral load (VL) [<500 copies/mL], reduced viral fitness, compromised sample collection/handling, primer incompatibility).	Baseline (Day 1)
Secondary	Percentage of Participants With Protocol-defined Virologic Failure (PDVF) at Week 24 and 48	Virologic failure is defined as: a) Virologic Nonresponse: HIV-1 RNA <1 log10 reduction from baseline, and HIV-1 RNA >= 400 copies/mL at the Week 12 visit, subsequently confirmed at an unscheduled visit conducted within 2 to 4 weeks after Week 12. b) Virologic Rebound: At any visit, after achieving confirmed consecutive HIV-1 RNA <50 copies/mL, a rebound in HIV 1 RNA to >= 50 copies/mL, which is subsequently confirmed at a scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result; or At any visit, a >1 log10 increase in HIV-1 RNA from the nadir, which is subsequently confirmed at the following scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result.	Week 24 and 48
Secondary	Percentage of Participants Developing Resistance-associated Mutation (RAMs) and Loss of Phenotypic Susceptibility, Upon Meeting Protocol-defined Virologic Failure (PDVF)	Percentage of participants developing RAMs and loss of phenotypic susceptibility, upon meeting PDVF were reported. Virologic failure is defined as: a) Virologic Nonresponse: HIV-1 RNA <1 log10 reduction from baseline, and HIV-1 RNA greater than or equal to (>=) 400 copies/mL at the Week 12 visit, subsequently confirmed at an unscheduled visit conducted within 2 to 4 weeks after Week 12. b) Virologic Rebound: At any visit, after achieving confirmed consecutive HIV-1 RNA <50 copies/mL, a rebound in HIV 1 RNA to >= 50 copies/mL, which is subsequently confirmed at a scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result; or At any visit, a >1 log10 increase in HIV-1 RNA from the nadir, which is subsequently confirmed at the following scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result.	Up to Week 48
Secondary	Percentage of Participants Lost-to-Follow-up Throughout the 48 Weeks of Treatment	Percentage of participants lost-to-follow-up throughout the 48 Weeks of treatment were reported.	Up to Week 48
Secondary	Percentage of Participants With Retention in Care Completed and With Documented Clinical Visit	Percentage of participants with retention in care completed and with documented clinical visit (within 90 days of discontinuation) were reported.	Up to Week 48
Secondary	Percentage of Participants With Treatment Adherence >95% Based on Pill Count at Weeks 4, 8, 12, 24, 36, and 48	Percentage of participants with treatment adherence >95% based on pill count at Weeks 4, 8, 12, 24, 36, and 48 were reported. Treatment adherence was defined as having a treatment adherence of greater than (>) 95 percent (%) by pill count.	Weeks 4, 8, 12, 24, 36, and 48
Secondary	Percentage of Participants With 100% Treatment Adherence Based on Participants Self-Report, Using a 4-Day Recall at Weeks 4, 8, 12, 24, 36, and 48	Percentage of participants with 100 % adherence based on participants self-report, using a 4-Day recall at Weeks 4, 8, 12, 24, 36, and 48 was reported.	Weeks 4, 8, 12, 24, 36, and 48
Secondary	Mean Total Scores for the HIV-Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4, 24, and 48	The HIV treatment satisfaction questionnaire (HIVTSQ) is based on a 10-item self-reported scale that measures overall satisfaction with treatment. The HIVTSQ items are summed up to produce a treatment satisfaction score (0 to 60) and an individual satisfaction rating for each item (0 to 6). The higher the score, the greater the treatment satisfaction.	Weeks 4, 24, and 48
Secondary	Number of Participants With Hospitalizations	Number of participants with hospitalizations (overnight) was reported.	Up to Week 48
Secondary	Duration of Hospitalizations	Duration of hospitalizations in days was reported for those participants hospitalized during the course of the study. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this OM.	Up to Week 48
Secondary	Number of Participants With Outpatient Visits	Number of participants with outpatient visits (in addition to study visits, including General practitioner visit, Specialist visit, Nurse practitioner visit, Physician assistant visit, Home healthcare nurse visit and Other visit) was reported.	Up to Week 48
Secondary	Number of Participants With Emergency Room Visits	Number of participants with emergency room visits was reported.	Up to Week 48
Secondary	Median Medical Costs of Care ((United States of America [USA] Dollars) Based on Healthcare Resource Utilization [HRU])	Median medical costs of care (United States of America [USA] dollars) based on healthcare resource utilization [HRU]) were reported. The cost of care specified for overnight hospitalization, hospital day care ward (without overnight), emergency room visit, general practitioner visit, specialist visit, nurse practitioner visit, physician assistant visit and Other visit.	Up to Week 48
Secondary	Percentage of Participants Discontinuing Therapy Due to Adverse Events (AEs) Through Week 96	Percentage of participants discontinuing therapy due to AEs were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Up to Week 96
Secondary	Percentage of Participants Experiencing Grade 3 and 4 Adverse Events Through Week 96	AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events.	Up to Week 96
Secondary	Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Through Week 96	Percentage of participants experiencing grade 3 and 4 laboratory abnormalities were assessed by Division of Acquired Immunodeficiency Syndrome (DAIDS) Adverse Event (AE) Grading Table. Abnormal laboratory values with Grade 3 or higher (3=Severe; 4=potentially life-threatening) signifies an interruption of usual daily activity, requiring systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable.	Up to Week 96
Secondary	Percentage of Participants With Protocol-defined Virologic Failure (PDVF) at Week 72 and 96	Virologic failure is defined as: a) Virologic Nonresponse: HIV-1 RNA <1 log10 reduction from baseline, and HIV-1 RNA >= 400 copies/mL at the Week 12 visit, subsequently confirmed at an unscheduled visit conducted within 2 to 4 weeks after Week 12. b) Virologic Rebound: At any visit, after achieving confirmed consecutive HIV-1 RNA <50 copies/mL, a rebound in HIV 1 RNA to >= 50 copies/mL, which is subsequently confirmed at a scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result; or At any visit, a >1 log10 increase in HIV-1 RNA from the nadir, which is subsequently confirmed at the following scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result.	Weeks 72 and 96