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

NCT01967940 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-292-01172013-002830-19
• Study Type: interventional
• Target: 55
• Locations: 5 countries
• Sites: 15

Brief Summary

The primary objective of this study is to evaluate the efficacy of tenofovir alafenamide (TAF) versus placebo, each administered with the existing, failing antiretroviral (ARV) regimen. There are 2 parts to this study: Part 1 and Part 2. Part 1 consists of 2 cohorts, starting with a sentinel cohort, in which participants will be enrolled to receive open-label TAF in addition to their current failing ARV regimen. This cohort will then be followed by a randomized, double-blind, cohort to compare the addition of TAF or placebo in HIV-1 positive adults who are failing their current ARV regimen. In Part 2, all participants who complete Part 1 of the study will discontinue their failing ARV regimen and TAF or placebo 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 (E/C/F/TAF) single-tablet regimen (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. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.

Conditions

HIV; HIV Infections; Acquired Immunodeficiency Syndrome

Keywords

HIV-1; HIV; Treatment-Experienced

Outcome Measures

Primary Outcomes (1)

• Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10

  Day 10

Secondary Outcomes (15)

• Part 1: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Day 10

  Baseline; Day 10

• Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 24

  Up to Week 24

• Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 48

  Up to Week 48

• Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 24

  Up to Week 24

• Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 48

  Up to Week 48

Study Arms (4)

Part 1 Sentinel Cohort (TAF)

EXPERIMENTAL

TAF + their current failing ARV regimen for 10 days in Part 1

Drug: TAF; Drug: Current failing ARV regimen

Part 1 Randomized Cohort (TAF)

EXPERIMENTAL

Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive TAF + their current failing ARV regimen for 10 days in Part 1.

Drug: TAF; Drug: Current failing ARV regimen

Part 1 Randomized Cohort (Placebo)

PLACEBO COMPARATOR

Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive placebo + their current failing ARV regimen for 10 days in Part 1.

Drug: Placebo; Drug: Current failing ARV regimen

Part 2 E/C/F/TAF+ATV

EXPERIMENTAL

Following a 14-day period to confirm eligibility, participants in the Randomized Cohort TAF group with a \> 0.5 log10 decline in HIV-1 RNA and all participants completing the Randomized Cohort Placebo group will receive E/C/F/TAF+ATV for 48 weeks in Part 2. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.

Drug: E/C/F/TAF; Drug: ATV

Interventions

TAF DRUG

25 mg tablet administered orally once daily with food

Also known as: Vemlidy®, GS-7340

Part 1 Randomized Cohort (TAF); Part 1 Sentinel Cohort (TAF)

Placebo DRUG

Tablets to match TAF administered orally once daily with food

Part 1 Randomized Cohort (Placebo)

E/C/F/TAF DRUG

150/150/200/10 mg STR administered orally once daily with food

Also known as: Genvoya®

Part 2 E/C/F/TAF+ATV

Current failing ARV regimen DRUG

Participants will continue taking their current ARV regimen as prescribed in Part 1.

Part 1 Randomized Cohort (Placebo); Part 1 Randomized Cohort (TAF); Part 1 Sentinel Cohort (TAF)

ATV DRUG

300 mg tablet administered orally once daily.

Also known as: Reyataz®

Part 2 E/C/F/TAF+ATV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Hepatitis B surface antigen (HBsAg) positive
• Hepatitis C antibody positive (individuals with positive hepatitis C virus (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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (15)

Midway Immunology and Research center

Ft. Pierce, Florida, 34982, United States

Location

Triple O Research Institute, P.A.

West Palm Beach, Florida, 33401, United States

Location

Rowan Tree Medical, P.A.

Wilton Manors, Florida, 33305, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Salvador B Gautier Hospital - Infectious Diseases Department

Santo Domingo, 10514, Dominican Republic

Location

Instituto Dominicano de Estudio Virologicos - IDEV

Santo Domingo, Dominican Republic

Location

Regional state budget health agency Krasnoyarsk Regional Center for Prevention and Control of AIDS

Krasnoyarsk, 660049, Russia

Location

Center For Prevention and Treatment of AIDS and Infectious Diseases, Saint Petersburg

Saint Petersburg, 190020, Russia

Location

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital, Mahidol University

Bangkok, 10400, Thailand

Location

Siriraj Hospital Department of Preventive and Social Medicine, Faculty of Medicine

Bangkok, 10700, Thailand

Location

Chiang Mai University

Chiang Mai, 50200, Thailand

Location

Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Joint Clinical Research Centre

Kampala, Uganda

Location

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

tenofovir alafenamide; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Atazanavir Sulfate

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Pyridines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Part 1 Sentinel Cohort: Open-label, non-randomized Part 1 Randomized Cohort: Double-blind, randomized Part 2: Open-label, non-randomized
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 (Sentinel Cohort followed by a Randomized Cohort), 14-day washout period, then Part 2

Study Record Dates

• First Submitted: October 18, 2013
• First Posted: October 23, 2013
• Study Start: October 25, 2013
• Primary Completion: May 21, 2015
• Study Completion: July 31, 2017
• Last Updated: November 16, 2018
• Results First Posted: June 12, 2017

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (5); DO (2); TH (5); UG (1); RU (2)