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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01968551
• Other study ID #: GS-US-292-0119
• Status: Completed
• Phase: Phase 3
• Start date: September 3, 2013
• Est. completion date: July 9, 2016

Study information

• Verified date: July 2017
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: July 9, 2016
• Est. primary completion date: July 21, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• HIV-1
• Immunologic Deficiency Syndromes

Intervention

Drug:
• E/C/F/TAF
150/150/200/10 mg FDC tablet administered orally once daily
• DRV
800 mg tablet administered orally once daily
• Baseline DRV- containing ARV regimen
Participants will take their baseline DRV- containing ARV regimen as prescribed.

Locations

Country	Name	City	State
Canada	Southern Alberta Clinic	Calgary	Alberta
Canada	Clinique médicale L'actuel	Montreal	Quebec
Canada	Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Maple Leaf Research	Toronto	Ontario
Canada	Vancouver ID Research & Care Centre Society	Vancouver	British Columbia
Canada	Wrha - Health Sciences Centre Winnipeg	Winnipeg	Manitoba
United States	Summa Health System CARE Center	Akron	Ohio
United States	Albany Medical College	Albany	New York
United States	Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)	Annandale	Virginia
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Atlanta ID Group	Atlanta	Georgia
United States	Pacific Oaks Medical Group	Beverly Hills	California
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Harvard Medical School	Boston	Massachusetts
United States	Carolinas Medical Center--Myer's Park	Charlotte	North Carolina
United States	Howard Brown Health Center	Chicago	Illinois
United States	The Ruth M. Rothstein CORE Center	Chicago	Illinois
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	North Texas infectious Diseases Consultants, PA	Dallas	Texas
United States	Midland Florida Clinical Research Center, LLC	DeLand	Florida
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Health System	Durham	North Carolina
United States	New York Hospital Queens	Flushing	New York
United States	Gary J.Richmond, MD, P.A.	Fort Lauderdale	Florida
United States	Therafirst Medical Center	Fort Lauderdale	Florida
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	East Carolina University The Brody School of Medicine, Infectious Diseases	Greenville	North Carolina
United States	Kaiser Permanente	Hayward	California
United States	Gordon E. Crofoot MD PA	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	The Kansas City Free Health Clinic/ KC Care Clinic	Kansas City	Missouri
United States	Long Beach Education and Research Consultants	Long Beach	California
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Peter J Ruane, MD, Inc.	Los Angeles	California
United States	Johns Hopkins University	Lutherville	Maryland
United States	Mercer University, Mercer Medicine	Macon	Georgia
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	Beth Israel Medical Center	New York	New York
United States	Weill Medical College	New York	New York
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	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University Of Pennsylvania	Philadelphia	Pennsylvania
United States	Pueblo Family Physicians, Ltd.	Phoenix	Arizona
United States	The Miriam Hospital	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	Kaiser Permanente Medical Group	Sacramento	California
United States	Central West Clinical Research	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Kaiser San Francisco Division of Research	San Francisco	California
United States	Southwest CARE Center	Santa Fe	New Mexico
United States	Peter Shalit, MD	Seattle	Washington
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Baystate Infectious Diseases Clinical Research	Springfield	Massachusetts
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	Dupont Circle Physician's Group	Washington	District of Columbia
United States	Triple O Research Institute PA	West Palm Beach	Florida
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

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.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at 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.	Week 24
Secondary	Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at 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.	Week 48
Secondary	Change From Baseline in CD4+ Cell Count at Week 24		Baseline; Week 24
Secondary	Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48