D/C/F/TAF Versus COBI-boosted DRV Plus FTC/TDF in HIV-1 Infected, Antiretroviral Treatment Naive Adults

Phase 2

Completed

• Conditions: Acquired Immunodeficiency Syndrome; HIV Infections
• Interventions: Drug: D/C/F/TAF; Drug: DRV; Drug: DRV Placebo; Drug: COBI; Drug: COBI Placebo; Drug: FTC/TDF; Drug: FTC/TDF Placebo; Drug: D/C/F/TAF Placebo

• Registration Number: NCT01565850
• Lead Sponsor: Gilead Sciences

Brief Summary

This study is to evaluate the safety and efficacy darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed dose combination (FDC) tablet versus darunavir (DRV)+cobicistat (COBI)+emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in HIV-1 infected, antiretroviral treatment-naive adults as determined by the achievement of HIV-1 RNA \< 50 copies/mL at Week 24.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-03-27
• Study First Submitted QC: 2012-03-27
• Study First Posted: 2012-03-29
• Study Start: 2012-04
• Primary Completion: 2013-01
• Disposition First Submitted: 2013-11-25
• Disposition First Submitted QC: 2013-11-25
• Disposition First Posted: 2013-12-19
• Study Completion: 2014-02
• Status Verified: 2016-03
• Results First Submitted: 2016-03-11
• Results First Submitted QC: 2016-03-11
• Last Update Submitted: 2016-03-11
• Results First Posted: 2016-04-11
• Last Update Posted: 2016-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 153

Inclusion Criteria

• Adult (≥ 18 years) males or non-pregnant females
• Ability to understand and sign a written informed consent form
• General medical condition which does not interfere with the assessments and the completion of the trial
• Plasma HIV-1 RNA levels ≥ 5,000 copies/mL
• CD4+ cell count > 50 cells/µL
• Treatment-naive: No prior use of any approved or experimental anti-HIV drug for any length of time
• Screening genotype report must show sensitivity to DRV, TDF and FTC
• Normal ECG
• Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula
• Hepatic transaminases ≤ 2.5 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL
• Serum amylase ≤ 5 x ULN
• Adequate hematologic function
• Normal thyroid-stimulating hormone (TSH)
• Females of childbearing potential must have a negative serum pregnancy test
• Females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drugs
• Female subjects who are postmenopausal must have documentation of cessation of menses for ≥ 12 months and hormonal failure
• Female subjects who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level test
• Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 90 days following discontinuation of investigational medicinal product

Exclusion Criteria

• A new AIDS defining condition diagnosed within the 30 days prior to screening
• Hepatitis B surface antigen positive
• Hepatitis C antibody positive
• Proven acute hepatitis in the 30 days prior to study entry
• Have a history or experiencing decompensated cirrhosis
• Current alcohol or substance use that potentially interferes with study compliance
• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements
• History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Female subjects who utilize non-estrogen hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
• Have an implanted defibrillator or pacemaker
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline
• Participation in any other clinical trial without prior approval is prohibited while participating in this trial
• Receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with darunavir and cobicistat
• Note: darunavir is a sulfonamide. Participants who previously experienced a sulfonamide allergy will be allowed to enter the trial. To date, no potential for cross sensitivity between drugs in the sulfonamide class and darunavir has been identified in patients participating in Phase 2 and Phase 3 trials.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
D/C/F/TAF	DRV Placebo	D/C/F/TAF FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo
D/C/F/TAF	COBI Placebo	D/C/F/TAF FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo
D/C/F/TAF	FTC/TDF Placebo	D/C/F/TAF FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo
D/C/F/TAF	D/C/F/TAF	D/C/F/TAF FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo
DRV+COBI+FTC/TDF	DRV	DRV tablet plus COBI tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo
DRV+COBI+FTC/TDF	COBI	DRV tablet plus COBI tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo
DRV+COBI+FTC/TDF	FTC/TDF	DRV tablet plus COBI tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo
DRV+COBI+FTC/TDF	D/C/F/TAF Placebo	DRV tablet plus COBI tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24	Week 24	The snapshot algorithm was used which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in HIV-1 RNA at Week 24	Baseline; Week 24
Change From Baseline in HIV-1 RNA at Week 48	Baseline; Week 48
Change From Baseline in CD4+ Cell Count at Week 48	Baseline; Week 48
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48	Week 48	The snapshot algorithm was used which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Change From Baseline in CD4+ Cell Count at Week 24	Baseline; Week 24

Trial Locations

Locations (44)

Peter J. Ruane, MD, Inc.; 🇺🇸 Los Angeles, California, United States

North Shore University Hospital / Division of Infectious Diseases; 🇺🇸 Manhasset, New York, United States

Southwest Infectious Disease Clinical Research Inc; 🇺🇸 Dallas, Texas, United States

Howard Brown Health Center; 🇺🇸 Chicago, Illinois, United States

Community Research Initiative (CRI); 🇺🇸 Boston, Massachusetts, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Clinical Research Puerto Rico; 🇵🇷 San Juan, Puerto Rico

Gary J. Richmond,M.D.,P.A.; 🇺🇸 Fort Lauderdale, Florida, United States

University of South Carolina School of Medicine Division of Infectious Disease; 🇺🇸 Columbia, South Carolina, United States

CARE-ID; 🇺🇸 Annandale, Virginia, United States

Kaiser Permanente; 🇺🇸 Los Angeles, California, United States

Mercer University Mercer Medicine; 🇺🇸 Macon, Georgia, United States

AHF Research Center; 🇺🇸 Beverly Hills, California, United States

Peter Shalit, M.D.; 🇺🇸 Seattle, Washington, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

La Playa Medical Group and Clinical Research; 🇺🇸 San Diego, California, United States

Kasier Permanente Medical Center; 🇺🇸 San Francisco, California, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Therapeutic Concepts, PA; 🇺🇸 Houston, Texas, United States

Gordon E. Crofoot, MD., PA; 🇺🇸 Houston, Texas, United States

St. Joseph's Comprehensive Research Institute; 🇺🇸 Tampa, Florida, United States

Anthony Mills MD, Inc; 🇺🇸 Los Angeles, California, United States

Alta Bates Summit Medical Center, East Bay AIDS Center; 🇺🇸 Oakland, California, United States

Kaiser Permanente Medical Group; 🇺🇸 Sacramento, California, United States

Apex Research; 🇺🇸 Denver, Colorado, United States

Capital Medical Associates, PC; 🇺🇸 Washington, District of Columbia, United States

Infectious Disease Specialists of Atlanta; 🇺🇸 Decatur, Georgia, United States

IDOCF/ValuhealthMD, LLC; 🇺🇸 Orlando, Florida, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

Denver Infectious Disease Consultants, PLLC; 🇺🇸 Denver, Colorado, United States

ID Consultants, P.A.; 🇺🇸 Charlotte, North Carolina, United States

Orange Coast Medical Group; 🇺🇸 Newport Beach, California, United States

Be Well Medical Center; 🇺🇸 Berkley, Michigan, United States

TPMG--Clinical Trials Unit; 🇺🇸 San Francisco, California, United States

Dupont Circle Physician's Group; 🇺🇸 Washington, District of Columbia, United States

Wohlfeiler, Piperato and Associates, LLC; 🇺🇸 Miami Beach, Florida, United States

Whitman-Walker Health; 🇺🇸 Washington, District of Columbia, United States

Central West Clinical Research Inc; 🇺🇸 St. Louis, Missouri, United States

DCOL Center for Clinical Research; 🇺🇸 Longview, Texas, United States

Tarrant County Infectious Disease Associates; 🇺🇸 Fort Worth, Texas, United States

Orlando Immunology Center; 🇺🇸 Orlando, Florida, United States