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

NCT ID: NCT01968551

Last Updated: 2018-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 158 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-03
• Study Completion Date: 2016-07-09

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.

Conditions

HIV-1; HIV Infections; Acquired Immunodeficiency Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

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.

Group Type: EXPERIMENTAL

E/C/F/TAF

Intervention Type: DRUG

150/150/200/10 mg FDC tablet administered orally once daily

DRV

Intervention Type: DRUG

800 mg tablet administered orally once daily

Cohort 2, Treatment Group 1

Participants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks.

Group Type: EXPERIMENTAL

E/C/F/TAF

Intervention Type: DRUG

150/150/200/10 mg FDC tablet administered orally once daily

DRV

Intervention Type: DRUG

800 mg tablet administered orally once daily

Cohort 2, Treatment Group 2

Participants will be randomized to continue on their baseline DRV-containing ARV regimen for 48 weeks.

Group Type: ACTIVE_COMPARATOR

Baseline DRV- containing ARV regimen

Intervention Type: DRUG

Participants will take their baseline DRV- containing ARV regimen as prescribed.

Interventions

E/C/F/TAF

150/150/200/10 mg FDC tablet administered orally once daily

Intervention Type: DRUG

DRV

800 mg tablet administered orally once daily

Intervention Type: DRUG

Baseline DRV- containing ARV regimen

Participants will take their baseline DRV- containing ARV regimen as prescribed.

Intervention Type: DRUG

Other Intervention Names

Genvoya®

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Pueblo Family Physicians, Ltd.

Phoenix, Arizona, United States

Pacific Oaks Medical Group

Beverly Hills, California, United States

Kaiser Permanente

Hayward, California, United States

Long Beach Education and Research Consultants

Long Beach, California, United States

Peter J Ruane, MD, Inc.

Los Angeles, California, United States

Kaiser Permanente Medical Group

Sacramento, California, United States

Kaiser San Francisco Division of Research

San Francisco, California, United States

Dupont Circle Physician's Group

Washington D.C., District of Columbia, United States

Midland Florida Clinical Research Center, LLC

DeLand, Florida, United States

Therafirst Medical Center

Fort Lauderdale, Florida, United States

Gary J.Richmond, MD, P.A.

Fort Lauderdale, Florida, United States

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Orlando Immunology Center

Orlando, Florida, United States

Valuhealthmd/Idocf

Orlando, Florida, United States

Infectious Diseases Associates of NW FL

Pensacola, Florida, United States

Hillsborough County Health Department

Tampa, Florida, United States

St. Joseph's Comprehensive Research Institute

Tampa, Florida, United States

AIDS Research and Treatment Center of the Treasure Coast

Vero Beach, Florida, United States

Triple O Research Institute PA

West Palm Beach, Florida, United States

Atlanta ID Group

Atlanta, Georgia, United States

AIDS Research Consortium of Atlanta

Atlanta, Georgia, United States

Mercer University, Mercer Medicine

Macon, Georgia, United States

The Ruth M. Rothstein CORE Center

Chicago, Illinois, United States

Howard Brown Health Center

Chicago, Illinois, United States

Johns Hopkins University

Lutherville, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Harvard Medical School

Boston, Massachusetts, United States

Baystate Infectious Diseases Clinical Research

Springfield, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Abbott Northwestern Hospital

Minneapolis, Minnesota, United States

The Kansas City Free Health Clinic/ KC Care Clinic

Kansas City, Missouri, United States

Central West Clinical Research

St Louis, Missouri, United States

South Jersey Infectious Disease

Somers Point, New Jersey, United States

Southwest CARE Center

Santa Fe, New Mexico, United States

Albany Medical College

Albany, New York, United States

New York Hospital Queens

Flushing, New York, United States

Beth Israel Medical Center

New York, New York, United States

Weill Medical College

New York, New York, United States

University of Rochester

Rochester, New York, United States

Carolinas Medical Center--Myer's Park

Charlotte, North Carolina, United States

Duke University Health System

Durham, North Carolina, United States

East Carolina University The Brody School of Medicine, Infectious Diseases

Greenville, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Summa Health System CARE Center

Akron, Ohio, United States

The Ohio State University Medical Center

Columbus, Ohio, United States

University Of Pennsylvania

Philadelphia, Pennsylvania, United States

Philadelphia FIGHT

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

The Miriam Hospital

Providence, Rhode Island, United States

North Texas infectious Diseases Consultants, PA

Dallas, Texas, United States

Therapeutic Concepts, PA

Houston, Texas, United States

Gordon E. Crofoot MD PA

Houston, Texas, United States

DCOL Center for Clinical Research

Longview, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)

Annandale, Virginia, United States

Peter Shalit, MD

Seattle, Washington, United States

Southern Alberta Clinic

Calgary, Alberta, Canada

Vancouver ID Research & Care Centre Society

Vancouver, British Columbia, Canada

Wrha - Health Sciences Centre Winnipeg

Winnipeg, Manitoba, Canada

Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Maple Leaf Research

Toronto, Ontario, Canada

Clinique médicale L'actuel

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

PMID: 27753684 (View on PubMed)

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.

Reference Type: BACKGROUND

Other Identifiers

GS-US-292-0119

Identifier Type: -

Identifier Source: org_study_id