Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF

• ClinicalTrials.gov Identifier: NCT02121795
• Recruitment Status: Completed
• First Posted: April 24, 2014
• Results First Posted: November 30, 2016
• Last Update Posted: March 12, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: April 22, 2014
• First Posted Date: April 24, 2014
• Results First Submitted Date: August 11, 2016
• Results First Posted Date: November 30, 2016
• Last Update Posted Date: March 12, 2020
• Actual Study Start Date: May 6, 2014
• Actual Primary Completion Date: August 12, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2020)

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis [ Time Frame: 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 participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

• Original Primary Outcome Measures (submitted: April 22, 2014): Proportion of participants with HIV-1 RNA < 50 copies/mL as defined by the FDA snapshot analysis [ Time Frame: Week 48 ]

Current Secondary Outcome Measures (submitted: February 28, 2020)

• Percentage Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 [ Time Frame: Baseline; Week 48 ]
  Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
• Percentage Change From Baseline in Spine BMD at Week 48 [ Time Frame: Baseline; Week 48 ]
  Spine BMD was assessed by DXA scan.
• Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis [ Time Frame: Week 48 ]
  The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
• Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline; Week 48 ]
• Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the FDA Snapshot Analysis [ Time Frame: Week 96 ]
  The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 as Defined by the FDA Snapshot Analysis [ Time Frame: Week 96 ]
  The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
• Percentage Change From Baseline in Hip BMD at Week 96 [ Time Frame: Baseline; Week 96 ]
  Hip BMD was assessed by DXA scan.
• Percentage Change From Baseline in Spine BMD at Week 96 [ Time Frame: Baseline; Week 96 ]
  Spine BMD was assessed by DXA scan.
• Change From Baseline in CD4+ Cell Count at Week 96 [ Time Frame: Baseline; Week 96 ]

Original Secondary Outcome Measures (submitted: April 22, 2014)

• Percent change from baseline in hip bone mineral density (BMD) [ Time Frame: Week 48 ]
• Percent change from baseline in spine BMD [ Time Frame: Week 48 ]
• Proportion of participants with HIV-1 RNA < 50 copies/mL as defined by the FDA snapshot analysis [ Time Frame: Week 96 ]
• Proportion of participants with HIV-1 RNA < 20 copies/mL as defined by the FDA snapshot analysis [ Time Frame: Weeks 48 and 96 ]
• Change from baseline in CD4+ cell count [ Time Frame: Weeks 48 and 96 ]
• Percent change from baseline in hip and spine BMD [ Time Frame: Week 96 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF
• Official Title: A Phase 3, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Positive Subjects Who Are Virologically Suppressed on Regimens Containing FTC/TDF

Brief Summary

This study will evaluate the efficacy of switching from emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) fixed dose combination (FDC) to emtricitabine/tenofovir alafenamide (F/TAF) FDC in HIV-1 positive participants who are virologically suppressed on regimens containing FTC/TDF.

This study will consist of a 96 week double-blind treatment period. After Week 96, all participants will continue on blinded study drug treatment and attend visits every 12 weeks until treatment assignments are unblinded. All participants will return for an unblinding visit and will be given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF is commercially available, or the sponsor terminates the F/TAF clinical development program.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: HIV-1 Infection

Intervention

• Drug: FTC/TDF
  200/300 mg FDC tablets administered orally once daily
  Other Name: Truvada®
• Drug: F/TAF
  Tablets administered orally once daily
  Other Name: Descovy®
• Drug: Allowed third antiretroviral agent
  An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted lopinavir (LPV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV; Sustiva®), rilpivirine (RPV; Edurant®), nevirapine (NVP;Viramune®), raltegravir (RAL; Isentress®), dolutegravir (DTG;Tivicay®), and maraviroc (MVC; Selzentry®).
• Drug: FTC/TDF Placebo
  Tablets administered orally once daily
• Drug: F/TAF Placebo
  Tablets administered orally once daily

Study Arms

• Experimental: F/TAF + 3rd Agent
  Participants will receive F/TAF (200/25 mg or 200/10 mg) plus FTC/TDF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks. Dosing of F/TAF will be dependent on the third agent of the participants' pre-existing treatment regimen.
  Interventions:

  • Drug: F/TAF
  • Drug: Allowed third antiretroviral agent
  • Drug: FTC/TDF Placebo
• Active Comparator: FTC/TDF + 3rd Agent
  Participants will receive FTC/TDF plus F/TAF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks.
  Interventions:

  • Drug: FTC/TDF
  • Drug: Allowed third antiretroviral agent
  • Drug: F/TAF Placebo

• Publications *: Gallant JE, Daar ES, Raffi F, Brinson C, Ruane P, DeJesus E, Johnson M, Clumeck N, Osiyemi O, Ward D, Morales-Ramirez J, Yan M, Abram ME, Plummer A, Cheng AK, Rhee MS. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial. Lancet HIV. 2016 Apr;3(4):e158-65. doi: 10.1016/S2352-3018(16)00024-2. Epub 2016 Mar 14.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 7, 2016): 668
• Original Estimated Enrollment (submitted: April 22, 2014): 660
• Actual Study Completion Date: March 1, 2019
• Actual Primary Completion Date: August 12, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• Currently receiving antiretroviral regimen containing FTC/TDF in combination with one third agent for ≥ 6 consecutive months prior to screening.
• Plasma HIV-1 RNA levels < 50 copies/mL for at least 6 months preceding the screening visit (measured at least twice using the same assay) and not experienced two consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year.
• Plasma HIV-1 RNA should be < 50 copies/mL at the screening visit.
• Normal electrocardiogram (ECG)
• Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × the upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (individuals with documented Gilbert's syndrome or with Atazanavir-associated hyperbilirubinemia may have total bilirubin up to 5 x ULN)
• Adequate hematologic function
• Serum amylase ≤ 5 × ULN
• Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active, or practice abstinence from screening throughout the duration of the study treatment and for 30 days following the last dose of the study drug.
• Females who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range.
• 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.

Key Exclusion Criteria:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
• Individuals experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
• Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg, osteoporosis)
• Females who are breastfeeding
• Positive serum pregnancy test
• Have an implanted defibrillator or pacemaker
• Current alcohol or substance use judged by the investigator to potentially interfere with study compliance
• A 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.
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit
• Individuals receiving ongoing therapy with any of the medications not to be used with FTC, TAF, TDF or other antiretroviral third agents.

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, France, Italy, Puerto Rico, United Kingdom, United States

Administrative Information

• NCT Number: NCT02121795
• Other Study ID Numbers: GS-US-311-1089; 2013-005138-39 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: February 2020