Clinical trial NCT01968551: Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults
Official title: A Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1
HIV Infections
Acquired Immunodeficiency Syndrome
Keywords: HIV-1
HIV
Treatment-Experienced
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-10-24
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed dose combination (FDC) plus darunavir (DRV) relative to current antiretroviral regimens (ARV) in virologically suppressed, HIV-1 positive participants with HIV-1 RNA \<50 copies/mL at Week 24.

This study consists of 48 weeks of open-label phase followed by an optional Extension Phase in which all the participants will receive E/C/F/TAF+DRV.


Eligibility criteria: Key Inclusion Criteria:

* Ability to understand and sign a written informed consent form
* History of at least two prior antiretroviral regimens, and history of resistance to at least two different classes of antiretroviral agents
* Plasma HIV-1 RNA levels \< 50 copies/mL at screening. Virologically suppressed on the current antiretroviral regimen containing darunavir 600 mg twice a day or 800 mg once daily continuously for ≥ 4 months preceding the screening visit and have maintained documented undetectable plasma HIV-1 RNA levels (\< 50 copies/mL) and must have documentation of genotype/phenotype prior to current regimen which shows no darunavir associated resistance mutation.
* Currently receiving raltegravir, elvitegravir, or dolutegravir (50 mg once daily, but not twice daily), or have never received integrase inhibitor, or have documentation of genotype/phenotype within 12 months prior to current regimen which must show no evidence of resistance to integrase inhibitors
* Normal ECG
* Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft Gault formula for creatinine clearance
* Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)
* Serum amylase ≤ 5 × ULN (individuals with serum amylase \> 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
* A female individual is eligible to enter the study if it is confirmed that she is:

  * Not pregnant or nursing
  * Of non-childbearing potential (i.e., women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women \> 54 years of age with cessation (for ≥ 12 months) of previously occurring menses), or
  * Of childbearing potential and agrees to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last study drug dose.
  * Female individuals who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.
* Male individuals must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.
* Male individuals must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.

Key Exclusion Criteria:

* A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4 cell count and/or percentage criteria)
* Hepatitis B surface antigen (HBsAg) positive
* Individuals receiving drug treatment for Hepatitis C, or individuals who are anticipated to receive treatment for Hepatitis C during the course of the study.
* Must not have Q151M, T69ins, or \> 3 thymidine analogue mutations (TAMS) present on documented historic genotype report
* Individuals experiencing decompensated cirrhosis
* Females who are breastfeeding
* Positive serum pregnancy test
* Have an implanted defibrillator or pacemaker
* Current alcohol or substance use that may interfere with individual's study compliance
* A 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.
* Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 visit
* Any other clinical condition or prior therapy that would make the individual unsuitable for the study or unable to comply with dosing requirements
* Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
* Individuals receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with elvitegravir, cobicistat, emtricitabine, TAF, or DRV; or individuals with any known allergies to the study drugs.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 48
timeFrame: Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline; Week 48
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pueblo Family Physicians, Ltd.
state: Arizona
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Hayward
country: United States
facility: Kaiser Permanente
state: California
city: Long Beach
country: United States
facility: Long Beach Education and Research Consultants
state: California
city: Los Angeles
country: United States
facility: Peter J Ruane, MD, Inc.
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: San Francisco
country: United States
facility: Kaiser San Francisco Division of Research
state: California
city: Washington
country: United States
facility: Dupont Circle Physician's Group
state: District of Columbia
city: DeLand
country: United States
facility: Midland Florida Clinical Research Center, LLC
state: Florida
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary J.Richmond, MD, P.A.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: Valuhealthmd/Idocf
state: Florida
city: Pensacola
country: United States
facility: Infectious Diseases Associates of NW FL
state: Florida
city: Tampa
country: United States
facility: Hillsborough County Health Department
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprehensive Research Institute
state: Florida
city: Vero Beach
country: United States
facility: AIDS Research and Treatment Center of the Treasure Coast
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute PA
state: Florida
city: Atlanta
country: United States
facility: Atlanta ID Group
state: Georgia
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University, Mercer Medicine
state: Georgia
city: Chicago
country: United States
facility: The Ruth M. Rothstein CORE Center
state: Illinois
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Lutherville
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Harvard Medical School
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Infectious Diseases Clinical Research
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Kansas City
country: United States
facility: The Kansas City Free Health Clinic/ KC Care Clinic
state: Missouri
city: Saint Louis
country: United States
facility: Central West Clinical Research
state: Missouri
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Santa Fe
country: United States
facility: Southwest CARE Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Flushing
country: United States
facility: New York Hospital Queens
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Weill Medical College
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center--Myer's Park
state: North Carolina
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University The Brody School of Medicine, Infectious Diseases
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Summa Health System CARE Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University Of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Dallas
country: United States
facility: North Texas infectious Diseases Consultants, PA
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot MD PA
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)
state: Virginia
city: Seattle
country: United States
facility: Peter Shalit, MD
state: Washington
city: Calgary
country: Canada
facility: Southern Alberta Clinic
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver ID Research & Care Centre Society
state: British Columbia
city: Winnipeg
country: Canada
facility: Wrha - Health Sciences Centre Winnipeg
state: Manitoba
city: Ottawa
country: Canada
facility: Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Research
state: Ontario
city: Montreal
country: Canada
facility: Clinique médicale L'actuel
state: Quebec
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Huhn GD, Tebas P, Gallant J, Wilkin T, Cheng A, Yan M, Zhong L, Callebaut C, Custodio JM, Fordyce MW, Das M, McCallister S. A Randomized, Open-Label Trial to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Darunavir in Treatment-Experienced HIV-1-Infected Adults. J Acquir Immune Defic Syndr. 2017 Feb 1;74(2):193-200. doi: 10.1097/QAI.0000000000001193.
citation: Greg Huhn, Pablo Tebas, Joel Gallant et al. Strategic Simplification: the Efficacy and Safety of Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Plus Darunavir (DRV) in Treatment-Experienced HIV-1-Infected Adults (NCT01968551). IDWeek; 2015 San Diego, CA Oct. 7-11.