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

Phase 3

Completed

• Conditions: HIV-1; HIV Infections; Acquired Immunodeficiency Syndrome
• Interventions: Drug: E/C/F/TAF; Drug: Baseline DRV- containing ARV regimen; Drug: DRV

• Registration Number: NCT01968551
• Lead Sponsor: Gilead Sciences

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2013-09-03
• Study First Submitted: 2013-09-26
• Study First Submitted QC: 2013-10-18
• Study First Posted: 2013-10-24
• Disposition First Submitted: 2015-04-16
• Disposition First Submitted QC: 2015-04-16
• Disposition First Posted: 2015-05-06
• Primary Completion: 2015-07-21
• Study Completion: 2016-07-09
• Results First Submitted: 2016-07-20
• Results First Submitted QC: 2016-09-14
• Results First Posted: 2016-11-01
• Status Verified: 2017-07
• Last Update Submitted: 2018-10-19
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 158

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	E/C/F/TAF	Participants will receive E/C/F/TAF FDC + DRV once daily with food for 48 weeks. Based on safety and efficacy data from Cohort 1 at Week 4, the participants will be randomized into Cohort 2. The participants in Cohort 1 will continue receiving E/C/F/TAF FDC + DRV through 48 weeks.
Cohort 2, Treatment Group 1	E/C/F/TAF	Participants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks.
Cohort 1	DRV	Participants will receive E/C/F/TAF FDC + DRV once daily with food for 48 weeks. Based on safety and efficacy data from Cohort 1 at Week 4, the participants will be randomized into Cohort 2. The participants in Cohort 1 will continue receiving E/C/F/TAF FDC + DRV through 48 weeks.
Cohort 2, Treatment Group 1	DRV	Participants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks.
Cohort 2, Treatment Group 2	Baseline DRV- containing ARV regimen	Participants will be randomized to continue on their baseline DRV-containing ARV regimen for 48 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 24	Week 24	The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, 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 CD4+ Cell Count at Week 48	Baseline; Week 48
Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 48	Week 48	The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, 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 (62)

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

The Miriam Hospital; 🇺🇸 Providence, Rhode Island, United States

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

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

Midway Immunology and Research Center; 🇺🇸 Fort Pierce, Florida, United States

AIDS Research and Treatment Center of the Treasure Coast; 🇺🇸 Vero Beach, Florida, United States

Johns Hopkins University; 🇺🇸 Lutherville, Maryland, United States

Triple O Research Institute PA; 🇺🇸 West Palm Beach, Florida, United States

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

Harvard Medical School; 🇺🇸 Boston, Massachusetts, United States

Peter Shalit, MD; 🇺🇸 Seattle, Washington, United States

Albany Medical College; 🇺🇸 Albany, New York, United States

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

Abbott Northwestern Hospital; 🇺🇸 Minneapolis, Minnesota, United States

Duke University Health System; 🇺🇸 Durham, North Carolina, United States

Pacific Oaks Medical Group; 🇺🇸 Beverly Hills, California, United States

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

Valuhealthmd/Idocf; 🇺🇸 Orlando, Florida, United States

Hillsborough County Health Department; 🇺🇸 Tampa, Florida, United States

Infectious Diseases Associates of NW FL; 🇺🇸 Pensacola, Florida, United States

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

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

University of Rochester; 🇺🇸 Rochester, New York, United States

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

East Carolina University The Brody School of Medicine, Infectious Diseases; 🇺🇸 Greenville, North Carolina, United States

Philadelphia FIGHT; 🇺🇸 Philadelphia, Pennsylvania, United States

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

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

Pueblo Family Physicians, Ltd.; 🇺🇸 Phoenix, Arizona, United States

Kaiser San Francisco Division of Research; 🇺🇸 San Francisco, California, United States

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

Kaiser Permanente; 🇺🇸 Hayward, California, United States

Therafirst Medical Center; 🇺🇸 Fort Lauderdale, Florida, United States

Long Beach Education and Research Consultants; 🇺🇸 Long Beach, California, United States

Midland Florida Clinical Research Center, LLC; 🇺🇸 DeLand, Florida, United States

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

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

Atlanta ID Group; 🇺🇸 Atlanta, Georgia, United States

AIDS Research Consortium of Atlanta; 🇺🇸 Atlanta, Georgia, United States

The Ruth M. Rothstein CORE Center; 🇺🇸 Chicago, Illinois, United States

Central West Clinical Research; 🇺🇸 Saint Louis, Missouri, United States

Southwest CARE Center; 🇺🇸 Santa Fe, New Mexico, United States

New York Hospital Queens; 🇺🇸 Flushing, New York, United States

Beth Israel Medical Center; 🇺🇸 New York, New York, United States

The Ohio State University Medical Center; 🇺🇸 Columbus, Ohio, United States

University Of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

The Kansas City Free Health Clinic/ KC Care Clinic; 🇺🇸 Kansas City, Missouri, United States

Carolinas Medical Center--Myer's Park; 🇺🇸 Charlotte, North Carolina, United States

Baystate Infectious Diseases Clinical Research; 🇺🇸 Springfield, Massachusetts, United States

South Jersey Infectious Disease; 🇺🇸 Somers Point, New Jersey, United States

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Southern Alberta Clinic; 🇨🇦 Calgary, Alberta, Canada

Summa Health System CARE Center; 🇺🇸 Akron, Ohio, United States

North Texas infectious Diseases Consultants, PA; 🇺🇸 Dallas, Texas, United States

Maple Leaf Research; 🇨🇦 Toronto, Ontario, Canada

Ottawa Hospital - General Campus; 🇨🇦 Ottawa, Ontario, Canada

Vancouver ID Research & Care Centre Society; 🇨🇦 Vancouver, British Columbia, Canada

Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID); 🇺🇸 Annandale, Virginia, United States

Wrha - Health Sciences Centre Winnipeg; 🇨🇦 Winnipeg, Manitoba, Canada

Clinique médicale L'actuel; 🇨🇦 Montreal, Quebec, Canada

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States