Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults - Full Text View

Purpose

Part 1 consists of 2 cohorts, starting with a sentinel cohort, in which 10 participants will be enrolled to receive open-label tenofovir alafenamide (TAF) in addition to their current failing antiretroviral (ARV) regimen. This cohort will then be followed by a randomized, double-blind, cohort to compare the addition of TAF or placebo-to-match TAF in HIV-1 positive adults who are failing their current ARV regimen. This randomized cohort will consist of approximately 90 participants.

In Part 2, all participants who complete Part 1 of the study will discontinue their failing ARV regimen and TAF or placebo-to-match TAF for a 14-day washout period. Following the washout period, all participants who received TAF in Part 1 and have a > 0.5 log10 decline in HIV-1 RNA will receive elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide single-tablet regimen (E/C/F/TAF STR) plus atazanavir (ATV) once daily for 48 weeks. Participants who received TAF who have a ≤ 0.5 log10 decline in HIV-1 RNA will be discontinued from the study and will not be eligible to continue into Part 2 of the study. All participants who received placebo in Part 1 will be eligible to participate in Part 2 regardless of their viral load change.

Condition	Intervention	Phase
HIV HIV Infections Acquired Immunodeficiency Syndrome	Drug: TAF Drug: Placebo to match TAF Drug: E/C/F/TAF Drug: Pre-existing ARV regimen Drug: ATV	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 3, Two Part Study to Evaluate the Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Emtricitabine Tenofovir Atazanavir Tenofovir Disoproxil Fumarate Atazanavir sulfate Elvitegravir Cobicistat Genvoya

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Proportion of participants with plasma HIV-1 RNA decreases from baseline exceeding 0.5 log10 copies/mL at Day 10 (Part 1) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from baseline in plasma HIV-1 RNA (log10 copies/mL) at Day 10 (Part 1) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
Percentage of participants with plasma HIV-1 RNA < 50 copies/mL [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
Percentage of participants with plasma HIV-1 RNA < 400 copies/mL [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
Change from baseline in plasma HIV-1 RNA (log10 copies/mL) [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
Change from baseline in CD4+ cell count (cells/µL) and percentage [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
Safety of E/C/F/TAF STR plus ATV measured by incidence of adverse events and monitoring of laboratory parameters from baseline to Weeks 24 and 48 [ Time Frame: Baseline to Week 24 and 48 ] [ Designated as safety issue: No ]
Safety data will be summarized.
Plasma pharmacokinetics (PK) parameter of TAF as measured by AUClast, Clast, and Cmax and PK parameter of tenofovir, ATV, and elvitegravir as measured by AUCtau, Ctau, and Cmax [ Time Frame: Week 4 to Week 12 ] [ Designated as safety issue: No ]
- AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration
- Clast is defined as the last observable concentration of drug
- Cmax is defined as the maximum observed concentration of drug in plasma
- AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
- Ctau is defined as the observed drug concentration at the end of the dosing interval


Enrollment:	55
Study Start Date:	August 2013
Estimated Study Completion Date:	October 2016
Primary Completion Date:	May 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TAF followed by E/C/F/TAF plus ATV Participants will be randomized to receive TAF plus their pre-existing ARV regimen for 10 days in Part 1, followed by a 14-day washout period. After this period, participants with a > 0.5 log10 decline in HIV-1 RNA will then receive E/C/F/TAF plus ATV for 48 weeks in Part 2.	Drug: TAF Tenofovir alafenamide (TAF) 25 mg tablet administered orally once daily with food Drug: E/C/F/TAF Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regiment (STR) administered orally once daily with food Other Name: Genvoya® Drug: Pre-existing ARV regimen Participants will continue taking their pre-existing ARV regimen as prescribed in Part 1. Drug: ATV ATV 300 mg tablet administered orally once daily.
Experimental: Placebo followed by E/C/F/TAF plus ATV Participants will receive placebo to match TAF plus their pre-existing ARV regimen for 10 days in Part 1, followed by a 14-day washout period, and then receive E/C/F/TAF plus ATV for 48 weeks in Part 2 regardless of HIV-1 RNA value.	Drug: Placebo to match TAF Placebo tablets to match TAF administered orally once daily with food Drug: E/C/F/TAF Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regiment (STR) administered orally once daily with food Other Name: Genvoya® Drug: Pre-existing ARV regimen Participants will continue taking their pre-existing ARV regimen as prescribed in Part 1. Drug: ATV ATV 300 mg tablet administered orally once daily.

Arms

Assigned Interventions

Experimental: TAF followed by E/C/F/TAF plus ATV

Participants will be randomized to receive TAF plus their pre-existing ARV regimen for 10 days in Part 1, followed by a 14-day washout period. After this period, participants with a > 0.5 log10 decline in HIV-1 RNA will then receive E/C/F/TAF plus ATV for 48 weeks in Part 2.

Drug: TAF

Tenofovir alafenamide (TAF) 25 mg tablet administered orally once daily with food

Drug: E/C/F/TAF

Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regiment (STR) administered orally once daily with food

Other Name: Genvoya®

Drug: Pre-existing ARV regimen

Participants will continue taking their pre-existing ARV regimen as prescribed in Part 1.

Drug: ATV

ATV 300 mg tablet administered orally once daily.

Experimental: Placebo followed by E/C/F/TAF plus ATV

Participants will receive placebo to match TAF plus their pre-existing ARV regimen for 10 days in Part 1, followed by a 14-day washout period, and then receive E/C/F/TAF plus ATV for 48 weeks in Part 2 regardless of HIV-1 RNA value.

Drug: Placebo to match TAF

Placebo tablets to match TAF administered orally once daily with food

Drug: E/C/F/TAF

Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regiment (STR) administered orally once daily with food

Other Name: Genvoya®

Drug: Pre-existing ARV regimen

Participants will continue taking their pre-existing ARV regimen as prescribed in Part 1.

Drug: ATV

ATV 300 mg tablet administered orally once daily.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
Currently taking a failing ARV regimen
Screening or historical genotype report showing either 1 to 3 thymidine-analogue mutations (TAMs) and/or K65R, as well as M184V/I
Plasma HIV-1 RNA ≥ 500 copies/mL but ≤ 100,000 copies/mL at screening
Normal ECG
Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
Alanine aminotransferase (AST)/aspartate aminotransferase (AST) ≤ 5 × the upper limit of the normal range (ULN)
Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
Adequate hematologic function
Serum amylase ≤ 5 × ULN
Females may enter the study if it is confirmed that she is:
- Not pregnant or nursing
- Of non-childbearing potential (ie, have had a hysterectomy, both ovaries removed, 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 study drug dosing
  - Females 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.
Males 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.
Males 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
Hepatitis B surface antigen (HBsAg) positive
Hepatitis C antibody positive (Subjects with positive HCV antibody and without detectable HCV RNA are permitted to enroll)
History of integrase inhibitor use
Screening or historical genotype reports shows Q151M or T69ins or more than 3 TAMs.
Screening or historical genotype report shows resistance to integrase inhibitors
Individuals experiencing decompensated cirrhosis
Current alcohol or substance use
History of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Part 1, Day 1 and must not be anticipated to require systemic therapy during the study.
Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Part 1, Day 1
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
Receiving ongoing therapy with any disallowed medications, including any drugs not to be used with elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide or known allergies to the excipients of E/C/F/TAF STR

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01967940

Show 35 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators


Study Director:	Hal Martin, MD, MPH	Gilead Sciences

More Information


Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01967940 History of Changes
Other Study ID Numbers:	GS-US-292-0117 2013-002830-19
Study First Received:	October 18, 2013
Last Updated:	May 20, 2016
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:


HIV-1 HIV Treatment-Experienced

Additional relevant MeSH terms:


HIV Infections Immunologic Deficiency Syndromes Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immune System Diseases Slow Virus Diseases Atazanavir Sulfate Tenofovir Cobicistat	Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination Emtricitabine HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2016