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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01967940
• Other study ID #: GS-US-292-0117
• Secondary ID: 2013-002830-19
• Status: Completed
• Phase: Phase 3
• Start date: October 25, 2013
• Est. completion date: July 31, 2017

Study information

• Verified date: July 2018
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: July 31, 2017
• Est. primary completion date: May 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, 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.

• Males 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

• 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

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

Intervention

Drug:
• TAF
25 mg tablet administered orally once daily with food
• Placebo
Tablets to match TAF administered orally once daily with food
• E/C/F/TAF
150/150/200/10 mg STR administered orally once daily with food
• Current failing ARV regimen
Participants will continue taking their current ARV regimen as prescribed in Part 1.
• ATV
300 mg tablet administered orally once daily.

Locations

Country	Name	City	State
Dominican Republic	Instituto Dominicano de Estudio Virologicos - IDEV	Santo Domingo
Dominican Republic	Salvador B Gautier Hospital - Infectious Diseases Department	Santo Domingo
Russian Federation	Regional state budget health agency Krasnoyarsk Regional Center for Prevention and Control of AIDS	Krasnoyarsk
Russian Federation	Center For Prevention and Treatment of AIDS and Infectious Diseases, Saint Petersburg	Saint Petersburg
Thailand	Ramathibodi Hospital, Mahidol University	Bangkok
Thailand	Siriraj Hospital Department of Preventive and Social Medicine, Faculty of Medicine	Bangkok
Thailand	The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)	Bangkok
Thailand	Chiang Mai University	Chiang Mai
Thailand	Khon Kaen University	Khon Kaen
Uganda	Joint Clinical Research Centre	Kampala
United States	Midway Immunology and Research center	Fort Pierce	Florida
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	Triple O Research Institute, P.A.	West Palm Beach	Florida
United States	Rowan Tree Medical, P.A.	Wilton Manors	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,  Dominican Republic,  Russian Federation,  Thailand,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10		Day 10
Secondary	Part 1: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Day 10		Baseline; Day 10
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant'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	Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant'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	Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24	The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant'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	Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48	The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant'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	Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 24		Baseline; Week 24
Secondary	Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 48		Baseline; Week 48
Secondary	Part 2: Change From Baseline in CD4+ Cell Count at Week 24		Baseline; Week 24
Secondary	Part 2: Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48
Secondary	Part 2: Change From Baseline in CD4+ Percentage at Week 24		Baseline; Week 24
Secondary	Part 2: Change From Baseline in CD4+ Percentage at Week 48		Baseline; Week 48