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 (…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety:
Adverse events and clinical laboratory tests and DXA
Efficacy:
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA < 50
copies/mL at Week 48 as defined by the Food and Drug Administration (FDA)
snapshot algorithm.
Pharmacokinetics:
The pharmacokinetics of TAF and RPV will be assessed. The PK of FTC and /or TFV
may be explored
Secondary outcome
Efficacy:
*The change from baseline in CD4+ cell count at Week 48.
Background summary
As treatment guidelines recommend early treatment of HIV-1 infection, there is
need for regimens offering enhanced product safety and tolerability,
effectiveness, and convenience for long-term treatment.
FTC/RPV/TAF
While TDF is an effective drug used broadly in the treatment of HIV-1 infection
as a part of multiple combination regimens, including Atripla, patients may
benefit from anticipated improvements in the safety profile with the
replacement of TDF with TAF. The development of FTC/RPV/TAF is expected to
provide an additional option for HIV-1 infected patients: a TAF-containing,
(NNRTI)-based FDC that can be administered as one tablet once daily with
improved renal and bone safety and avoiding the central nervous system side
effects, rash, elevations in plasma lipids, or possible teratogenicity
associated with efavirenz.
This study will evaluate the safety, efficacy and tolerability of switching
from Atripla to FTC/RPV/TAF, thereby assessing the viability of FTC/RPV/TAF as
a FDC option for HIV-infected patients.
Study objective
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).
Secundairy 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 in a subset of
subjects.
- To evaluate the safety and tolerability of the two treatment arms
through Week 48.
Study design
Randomized, double-blind, multicenter study to evaluate the efficacy and safety
of FTC/RPV/TAF FDC versus continuing EFV/FTC/TDF FDC (Atripla*) in HIV-1
infected subjects who have been who have been virologically suppressed (HIV-1
RNA < 50 copies/mL) on a stable regimen of EFV/FTC/TDF FDC for > 6 consecutive
months at
Screening. Subjects will be randomized in a 1:1 ratio to one of the following
two
treatment arms:
Treatment Arm 1:
FDC of emtricitabine 200 mg/rilpivirine 25 mg/tenofovir alafenamide 25 mg
(FTC/RPV/TAF) QD + Placebo to match FDC of efavirenz 600 mg/emtricitabine 200
mg/tenofovir disoproxil fumarate 300 mg (EFV/FTC/TDF, Atripla) QD (n = 400)
Treatment Arm 2:
FDC of efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300
mg (EFV/FTC/TDF) QD + Placebo to match emtricitabine 200 mg/rilpivirine 25
mg/tenofovir alafenamide 25 mg (FTC/RPV/TAF) QD (n = 400)
Subjects will be treated for at least 48 weeks. After the last subject
completes the Week 48 visit and Gilead completes the Week 48 analysis, all
subjects will attend the Unblinding Visit, at which point subjects will be
given the option to receive FTC/RPV/TAF FDC in an
open label extension phase for 48 weeks (except in the United Kingdom [UK]) or
until Gilead Sciences elects to terminate the study, whichever occurs first.
Subjects who complete the study through Week 48 and do not wish to participate
in the open label extension will be required to return to the clinic 30 days
after the completion of the study drug for a 30-Day
Follow-up Visit.
After the Unblinding Visit, subjects in the UK will stop taking their study
drug and complete a 30 day follow up visit.
Intervention
Test Product, Dose, and Mode of Administration:
Emtricitabine 200 mg/rilpivirine 25 mg/tenofovir alafenamide 25 mg
(FTC/RPV/TAF) FDC administered orally QD with food
Reference Therapy, Dose, and Mode of Administration:
Efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg
(EFV/FTC/TDF, Atripla) FDC administered orally QD at bedtime on an empty
stomach
Study burden and risks
Laboratory analyses (hematology, chemistry, and urinalysis), HIV-1 RNA, CD4+
cell count, and complete or symptom directed physical examinations will be
performed at the Screening, Baseline/Day 1, and all subsequent study visits.
Subjects will be treated for at least
48 weeks. Blood and urine for selected bone and renal safety evaluations will
be collected at Baseline/Day 1, Weeks 24, 48, Unblinding and ESDD (if
applicable).
Blood for pharmacokinetic analysis will be collected at Weeks 4, 8, 12 and 24.
DXA scans will be performed prior to study drug administration at Baseline/Day
1, and then every 24 weeks throughout the study and at the Early Study Drug
Discontinuation Visit, if > 12 weeks since last scan (except in Germany where
DXA will not be collected). Scans
will cover the spine and hip to measure changes in bone mineral density.
Subjects will be treated for at least 48 weeks. After the last subject
completes the Week 48 visit and Gilead completes the Week 48 analysis, all
subjects will attend the Unblinding Visit,at which point subjects will be given
the option to receive FTC/RPV/TAF FDC in an
open label extension phase for 48 weeks (except in the UK) or until Gilead
Sciences elects to terminate the study, whichever occurs first.
Subjects who complete the study through Week 48 and do not wish to participate
in the open label extension will be required to return to the clinic 30 days
after the completion of the study drug for a 30-Day
Follow-up Visit.
After the Unblinding Visit, subjects in the UK will stop taking their study
drug and complete a 30 day follow up visit.
Flowers Building, Granta Park .
Abington, Cambridge CB21 6GT
GB
Flowers Building, Granta Park .
Abington, Cambridge CB21 6GT
GB
Listed location countries
Age
Inclusion criteria
Medically stable HIV-1 infected subjects who meet the following criteria:
* Currently receiving antiretroviral therapy consisting only of EFV/FTC/TDF FDC (Atripla) continuously for * 6 months preceding the Screening visit
* 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. Unconfirmed virologic elevation of * 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or *blip*) and prior to screening is acceptable
* HIV-1 RNA < 50 copies/mL at the Screening visit
* Adequate renal function defined as having an estimated glomerular filtration rate (eGFR) * 50 mL/min as calculated by the Cockcroft Gault
* 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)
* Hepatitis B surface antigen (HBsAg) negative
Exclusion criteria
* Hepatitis C antibody positive with detectable HCV RNA (subjects who have HCV antibody but no detectable HCV RNA are eligible to enroll) No anticipated need to initiate prohibited medications during the study
* 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-004779-21-NL |
| ClinicalTrials.gov | NCT02345226 |
| CCMO | NL52761.100.15 |