The purpose of this study is to evaluate if F/R/TAF works as well as Eviplera. It is also to see if F/R/TAF will maintain the control of your HIV-1 infection when compared to Eviplera. Safety, how well your body accepts the drug, will be evaluated

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2014-004545-27-NL
• Date of registration: 23/03/2015
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: The purpose of this study is to evaluate if F/R/TAF works as well as Eviplera. It is also to see if F/R/TAF will maintain the control of your HIV-1 infection when compared to Eviplera. Safety, how well your body accepts the drug, will be evaluated
• Scientific title: A Phase 3b, Randomized, Double-Blind Switch Study to Evaluate the Safety and Efficacy of Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) Fixed Dose Combination (FDC) in HIV-1 Positive Subjects who are Virologically Suppressed on Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF)
• Date of first enrolment: 08/06/2015
• Target sample size: 550
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004545-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Medical monitor
• Affiliation: Gilead Sciences, Inc.

• Name: Medical monitor
• Affiliation: Gilead Sciences, Inc.

Key inclusion & exclusion criteria

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 FTC/RPV/TDF FDC for = 6 consecutive months preceding the Screening visit
4. Documented plasma HIV-1 RNA levels < 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) for = 6 months preceding the Screening visit. After reaching HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA = 50 copies/mL followed by resuppression are allowed
5. Have no documented resistance to any of the study agents at any time in the past, including but not limited to the reverse transcriptase resistance mutations K65R, K70E, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C, M230I/L, the combination of K103N+L100I , or 3 or more thymidine analog associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R)
6. HIV-1 RNA < 50 copies/mL at the Screening visit
7. Hepatic transaminases (AST and ALT) = 5 × upper limit of normal (ULN)
8. Total bilirubin = 1.5 mg/dL (= 26µmol/L), or normal direct bilirubin
9. Adequate hematologic function (absolute neutrophil count = 1,000/mm3 (1.00 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. Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
12. Adequate renal function: Estimated glomerular filtration rate ? 50 mL/min (1.17 mL/sec) according to the Cockcroft-Gault formula
13. A female subject is eligible to enter the study if it is confirmed that she is:
a) Not pregnant or nursing
b) Of non-childbearing potential (i.e., women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women
> 54 years of age with cessation (for = 12 months) of previously occurring menses), or
c) Of childbearing potential and agrees to utilize highly effective protocol-specified contraceptive method or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last study drug dose
d) Female subjects 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
14. Male subjects 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
15. Male subjects must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.
Exclusion criteria:
1. Hepatitis B surface antigen (HBsAg) positive
2. Hepatitis C antibody positive with detectable HCV RNA (subjects who have HCV antibody but no detectable HCV RNA are eligible to enroll)
3. Subjects experiencing or with a medical history of decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
4. Females who are breastfeeding
5. Positive serum pregnancy test
6. Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
7. 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. Subjects with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline/Day 1 and must not be
anticipated to require systemic therapy during the study
8. Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline/Day 1
9. 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 dosing requirements
10. Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
11. Subjects receiving ongoing therapy with any of the specified medications in the protocol, including drugs not to be used with FTC, RPV and/or TAF (refer to the individual agents Prescribing Information); or subjects with any known allergies to the excipients of
FTC/RPV/TAF


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Human Immunodeficiency Virus (HIV-1) Infection
MedDRA version: 20.0 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000020174

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: Emtricitabine/Rilpivirine/Tenofovir Alafenamide 200 mg/25 mg/25 mg film coated tablets
Product Code: FTC/RPV/TAF
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EMTRICITABINE
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: Rilpivirine
CAS Number: 500287-72-9
Other descriptive name: RILPIVIRINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: TENOFOVIR ALAFENAMIDE
CAS Number: 379270-37-8
Other descriptive name: TENOFOVIR ALAFENAMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Eviplera
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Rilpivirine
CAS Number: 500287-72-9
Other descriptive name: RILPIVIRINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: EMTRICITABINE
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: TENOFOVIR DISOPROXIL
Other descriptive name: TENOFOVIR DISOPROXIL
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration numb

Primary Outcome(s)

Secondary Objective: To determine the safety of the two treatment arms as determined by the percent change from baseline in hip and spine bone mineral density as assessed by dual energy X-ray absorptiometry (DXA) at Week 48 and 96 in a subset of subjects

To evaluate the safety and tolerability of the two treatment arms through Week 48

To evaluate the efficacy, safety and tolerability of the two treatment arms through Week 96

Main Objective: To evaluate the non-inferiority of switching to the FTC/RPV/TAF FDC as compared to continuing FTC/RPV/TDF FDC in
virologically suppressed HIV-1 infected subjects as determined by maintaining HIV-1 RNA < 50 copies/mL at Week 48 (FDA Snapshot Algorithm)

Primary end point(s): The primary analysis will consist of a non-inferiority evaluation of switching to FTC/RPV/TAF FDC versus continuing FTC/RPV/TDF
FDC, with respect to the proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 after the start of treatment in this study
(as defined by the FDA snapshot algorithm).

Timepoint(s) of evaluation of this end point: 48 Weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 48 and 96 weeks

Secondary end point(s): The proportion of subjects with HIV-1 RNA = 50 copies/mL at Weeks 48 and 96, and the proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 96, as defined by the US FDA-defined snapshot algorithm.

The comparison of FTC/RPV/TAF versus FTC/RPV/TDF, with respect to the percent change from baseline in hip and spine bone
mineral density (BMD) in DXA substudy will be conducted using Analysis of Variance (ANOVA) model, including treatment group as
a fixed effect in the model.

The AE and clinical laboratory data will be summarized using descriptive statistics.

Secondary ID(s)

2014-004545-27-SE

GS-US-366-1216

Source(s) of Monetary Support

Gilead Sciences, Inc.

Ethics review

Status: Approved
Approval date:
Contact: