The primary objective of this study is:- To assess the rates of HIV-1 infection in men who have sex with men (MSM) and transgender women (TGW) who have sex with men who are administered daily emtricitabine/tenofovir alafenamide (F/TAF) or…
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Brief title
Condition
- Other condition
Synonym
Health condition
HIV preventie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The randomization for this study is a 1:1 ratio, which means that the subjects
chance of being assigned to Treatment Arm 1 (F/TAF) and Treatment Arm 2 (F/TDF,
(Truvada)) is equal. the subject will take two tablets daily. Everybody
participating in this study will get one active treatment.
Treatment Arm 1: F/TAF 200mg/25mg and placebo to match F/TDF
Treatment Arm 2: F/TDF 200mg/300mg and placebo to match F/TAF
Taking part in this study will last about 292 weeks, including the screening
visit.
During the first part of the study, which is called the double-blind phase, the
subject will receive either F/TAF or F/TDF (Truvada) for at least 96 weeks. The
exact duration of participation in the double-blind phase depends on when the
subject enrolled in the study.
During the study, the subject will be required to visit the clinic at least 28
times over 292 weeks, including a 30-day follow-up visit at the end of the
study.
Secondary outcome
3.1.2. Secondary Endpoints
The key (α-controlled) secondary endpoints in the blinded phase are:
•The percent change from baseline in hip BMD at Week 48 in a subset of subjects
•The percent change from baseline in spine BMD at Week 48 in a subset of
subjects
•Assessment of renal biomarkers at Week 48
- percent change from baseline in urine beta-2-microglobulin to creatinine ratio
- percent change from baseline in urine RBP to creatinine ratio
- distribution of UP and UPCR categories
•The change from baseline in serum creatinine at Week 48
Other secondary endpoints include:
•The incidence of HIV-1 infection (as per Appendix 7) per 100 PY when all
subjects have 96 weeks of follow-up after randomization
•The percent change from baseline in hip and spine BMD at Week 96 in the
blinded phase in a subset of subjects (not in the Netherlands)
•The change from baseline in serum creatinine at Week 96 in the blinded phase
•The incidence of treatment-emergent adverse events and laboratory toxicities
• Assessment of renal biomarkers at Week 96 in the blinded phase
- percent change from baseline in urine beta-2-microglobulin to creatinine ratio
- percent change from baseline in urine RBP to creatinine ratio
- distribution of UP and UPCR categories
•The change from baseline in serum creatinine at Week 96 in the blinded phase
•The incidence of treatment-emergent adverse events and laboratory toxicities
3.1.3. Other Endpoints of Interest
•The intracellular TFV-DP and FTC-TP trough concentrations (Ctrough) in PBMCs.
•The adherence rate using plasma FTC and/or TFV levels
•The incidence of HIV-1 infection per 100 PY at OL Week 48 for those who
randomize to the F/TAF arm at baseline
•From the OL phase baseline to OL Week 48, percentage change in hip and spine
BMD (in a subset of subjects), assessment of renal biomarkers (percent change
in urine beta-2-microglobulin to creatinine ratio and urine RBP to creatinine
ratio, distribution of UP and UPCR categories), and change from baseline in
serum creatinine for those who switch to F/TAF from F/TDF in the OL phase
•The type and frequency of sexual practices that are associated with increased
risk of HIV-1 infection
Background summary
The purpose of this study is to see if Emtricitabine and Tenofovir Alafenamide
(F/TAF) is safe and effective for use as prevention of HIV-1 infection, also
known as Pre Exposure Prophylaxis (PrEP) in healthy adults.
Study objective
The primary objective of this study is:
- To assess the rates of HIV-1 infection in men who have sex with men (MSM) and
transgender women (TGW) who have sex with men who are administered daily
emtricitabine/tenofovir alafenamide (F/TAF) or emtricitabine/tenofovir
disoproxil fumarate (F/TDF) with a minimum follow-up of 48 weeks and at least
50% of subjects have 96 weeks of follow-up after randomization
The secondary objectives of this study are:
- To compare bone safety between the treatments as determined by dual energy
x-ray absorptiometry (DXA) tests of hip and spine bone mineral density (BMD) in
a subset of subjects at Week 48 and Week 96 in the blinded phase
- To compare renal safety between the treatments as determined by urine
retinol-binding protein (RBP) to creatinine ratio, urine beta-2-microglobulin
to creatinine ratio, urine protein to creatinine ratio (UPCR), and serum
creatinine at Week 48 and Week 96 in the blinded
phase
- To assess the rates of HIV-1 infection in MSM and TGW who have sex with men
who are administered daily F/TAF or F/TDF when all subjects have 96 weeks of
follow-up after randomization
- To compare the general safety between the treatments
Exploratory objectives of this study include:
- To evaluate the pharmacokinetics (PK) of intracellular tenofovir diphosphate
(TFV-DP) and emtricitabine-triphosphate (FTC-TP) in peripheral blood
mononuclear cells (PBMCs)
- To assess the adherence rate using TFV-DP levels in dried blood spot (DBS)
along with FTC and/or tenofovir (TFV) levels in plasma
- To evaluate the long term safety and rate of HIV-1 infections during the open
label (OL) phase following the blinded phase for subjects who received F/TAF
during the blinded phase
- To evaluate changes in renal and bone safety for those who switch to OL F/TAF
from blinded F/TDF following the blinded phase
- To evaluate the type and frequency of sexual practices that are associated
with increased risk of HIV-1 infection
Study design
Randomized, double-blind comparison of the safety and efficacy of F/TAF versus
F/TDF administered orally once daily.
All subjects must meet all eligibility criteria in order to receive treatment
in the study. Once randomized to receive treatment in the study, all subjects
must return to the study center for required visits at Weeks 4, 12, and every
12 weeks thereafter.
All subjects will remain blinded to study treatment for at least 96 weeks. The
primary endpoint data will be collected and analyzed when all subjects have a
minimum follow up of 48 weeks and 50% of the subjects have 96 weeks of follow
up after randomization.
Once all subjects have at least 96 weeks of follow up after randomization and
upon notification by Gilead, all subjects will return to the study center for
an end of blinded treatment phase visit (may coincide with their next scheduled
visit).
Subjects who are still on blinded study drug at the end of blinded treatment
phase visit will be offered entry into the OL phase of the study. Subjects who
continue participation in the OL phase will be administered F/TAF once daily
and will return to the study center for visits every 12 weeks up to OL Week 96.
Subjects who have discontinued study drug prior to the end of blinded treatment
phase visit due to HIV infection will be eligible to continue participation in
the OL phase up to OL Week 48, but will not be administered F/TAF once daily.
From OL Week 48 subjects who acquire HIV must complete the early study drug
discontinuation (ESDD) visit and discontinue the study at the 30 Day Follow-up
visit, 30 days after the last dose of study drug. Subjects who have
discontinued study drug for any other reason prior to the end of blinded
treatment phase visit will not be eligible to participate in the OL phase.
Subjects who remain on study at OL Week 96 will have the option to continue in
the OL extension phase and attend study visits every 12 weeks through OL Week
144, after which the study will complete and subjects will transition to
locally available HIV prevention services. Subjects who have been diagnosed and
confirmed as HIV positive during this phase must complete the ESDD visit and
discontinue the study at the 30-Day Follow Up visit, 30 days after the last
dose of study drug.
During the blinded treatment phase, subjects may choose to continue to
participate in the study without taking study drug (*on-study, off-study
drug*). Subjects who permanently discontinue study drug and continue to attend
normal study visits (at minimum one visit at least 30 days after last dose) are
not required to complete the follow-up visit. Any subject who has an ESDD visit
and who will not continue participating in the study, or any subject who will
not continue participation in the OL phase of the study, must complete the
30-Day Follow-Up visit 30 days after the last dose of study drug.
DXA scans will be performed during regular intervals throughout the study
(blinded and OL phase) in a subset of approximately 400 subjects at a subset of
sites (excluding Germany).
Study burden and risks
During the study, you will be required to visit the clinic at least 28 times
over 292 weeks, including a 30-day follow-up visit at the end of the study.
Burden, -questionnaires blood drawn at every visit. Swab samples from mouth
and rectum.
Collecting blood samples. The collection of these samples may cause pain,
bruising, lightheadedness, fainting, and very rarely, infection at the site of
the needle stick.
See appendix 2&3 Protocol amendment 6 dd 10Nov2020.
The study may provide extra knowledge and information regarding preventing
HIV-1
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GB
Listed location countries
Age
Inclusion criteria
1) HIV-1 negative status
2) MSM or TGW (male at birth) who have at least one of the following:
a) condomless anal intercourse with at least two unique male partners
in the past 12 weeks (partners must be either HIV-infected or of
unknown HIV status)
b) documented history of syphilis in the past 24 weeks
c) documented history of rectal gonorrhea or chlamydia in the past 24
weeks
3) Age >= 18 years
4) Estimated GFR >= 60 mL/min according to the Cockcroft-Gault formula
for creatinine clearance
5) Adequate liver and hematologic function
6) Willing and able to comply with study procedures
Exclusion criteria
1) Known hypersensitivity to the IMP, the metabolites, or formulation
excipient
2) Have a suspected or known active, serious infection(s)
3) Acute viral hepatitis A, B or C or evidence of chronic hepatitis B infection.
Subjects found to be susceptible to HBV infection should be referred for
HBV vaccination. Subjects found to be positive for HCV at screening must not
have active infection or must have completed treatment and achieved a sustained
virologic response.
4) Need for continued use of any contraindicated concomitant
medications
5) Have an implanted defibrillator or pacemaker
6) Have a history of osteoporosis or bone fragility fractures
7) Current alcohol or substance abuse judged by the Investigator to be
problematic such that it potentially interferes with subject study
compliance
8) Grade 3 or Grade 4 proteinuria or glycosuria that is unexplained or
not clinically manageable
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) Have received investigational agents for the treatment or prevention of
HIV-1 infection in the 30 days prior to screening.
11) Participation in any other clinical trail (including observational trails)
without prior approval from the sponsor is prohibited while participating in
this trial.
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 | EUCTR2016-001399-31-NL |
| CCMO | NL58586.018.16 |