This study will test an experimental drug called GS-9883/F/TAF (GS-9883/emtricitabine/tenofovir alafenamide) fixed dose combination (FDC) for the treatment of HIV-1 infection. The purpose of this study is to test the effectiveness of switching to GS-9883/F/TAF FDC versus continuing on DTG and ABC/3TC as the FDC ABC/DTG/3TC in HIV-1 infected adults who are virologically suppressed (HIV-1 RNA test <50 copies/mL)

Phase 1

Conditions: Human Immunodeficiency Virus (HIV-1) Infection
MedDRA version: 20.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2015-004025-14-GB

Lead Sponsor: Gilead Science, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 520

Inclusion Criteria

1. The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
2. Age = 18 years.
3. Currently receiving an antiretroviral regimen of DTG + ABC/3TC, or ABC/DTG/3TC FDC for = 3 months prior to the screening visit.
4. HIV RNA < 50 copies/mL at the screening visit.
5. Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant).
6. Adequate renal function:
Estimated glomerular filtration rate = 50 mL/min (= 0.83 mL/sec) according to the Cockcroft-Gault formula.
7. Hepatic transaminases (AST and ALT) = 5 x upper limit of normal (ULN).
8. Total bilirubin = 1.5 mg/dL (= 26 umol/L), or normal direct bilirubin.
9. Adequate hematologic function (absolute neutrophil count = 750/mm3 (= 0.75 GI/L);
platelets = 50,000/mm3 (= 50 GI/L); hemoglobin = 8.5 g/dL (= 85 g/L))
10. Serum amylase = 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if
serum lipase is = 5 × ULN).
11. Females of childbearing potential must agree to utilize protocol recommended highly
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence
from screening, throughout the duration of the study period, and for 30 days following the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods
must have used the same method for at least 3 months prior to study drug dosing.
12. Male subjects who engage in heterosexual intercourse must agree to use protocol specified
method(s) of contraception throughout the study period and for 90 days following the last dose of study drug.
13. Male subjects must agree to refrain from sperm donation from first study drug dose until at
least 90 days following the last study drug dose.
14. Life expectancy = 1 year.
15. Currently on a stable regimen for = 3 months preceding the Screening visit with documented plasma HIV-1 RNA
< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is = 50 copies/mL).
Prior changes in antiretroviral regimen are only allowed due to tolerability issues or for regimen simplification. Unconfirmed virologic elevations of = 50 copies/mL (transient detectable viremia, or blip”) prior to screening are acceptable. If the lower limit of detection of the local HIV-1 RNA assay is <50 copies/mL (eg, <20 copies/mL), the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests.
16. Have no documented or suspected resistance to FTC, TFV, DTG, ABC or 3TC including, but
not limited, to the reverse transcriptase resistance mutations K65R and M184V/I.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 430
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

1) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
2) Subjects experiencing decompensated cirrhosis (e.g, ascites, encephalopathy, or variceal bleeding)
3) Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (e.g, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
4) Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
5) A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not anticipated to require systemic therapy during the study
6) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
7) Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
8) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements
9) Any known allergies to the excipients of GS-9883/F/TAF FDC or ABC/DTG/3TC FDC tablets
10) Females who are pregnant (as confirmed by positive serum pregnancy test)
11) Females who are breastfeeding
12) Subjects receiving ongoing therapy with any of the following medications, Dofetilide, Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine, Rifampin, Rifapentine, Any antiretroviral drug that is not part of the study regimen,Cisapride, St. John’s Wort, Echinaccea, including drugs not to be used with FTC, TAF, GS-9883, DTG, ABC and 3TC
13) Acute hepatitis in the 30 days prior to study entry
14) Chronic Hepatitis B Virus (HBV) infection, as determined by either:
a) Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit
b) Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit
15) Active tuberculosis infection

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: To evaluate the efficacy of switching from a regimen of DTG and ABC/3TC or a fixed dose combination (FDC) of ABC/DTG/3TC to a FDC of<br> GS-9883/F/TAF versus continuing DTG and ABC/3TC as the FDC ABC/DTG/3TC in virologically suppressed HIV-1 infected subjects as determined by the proportion of subjects with virologic failure (HIV-1 RNA = 50 copies/mL) at Week 48.<br> ;<br> Secondary Objective: - To evaluate the safety and tolerability of the two treatment groups through Week 48<br> - To evaluate the bone safety of the two treatment groups as determined by the percentage change from baseline in hip and spine bone mineral density (BMD) through Week 48<br> ;Primary end point(s): The proportion of subjects with virologic failure (HIV-1 RNA = 50 copies/mL) at Week 48 as defined by the modified US FDA-defined snapshot algorithm.;Timepoint(s) of evaluation of this end point: At Week 48

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): - The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm.<br> - The change from baseline in CD4+ cell count at Week 48<br> - The percentage change from baseline in hip and spine BMD at Week 48<br> ;Timepoint(s) of evaluation of this end point: At Week 48

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