| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteers (Pre-exposure prophylaxis (PrEP) of human immunodeficiency virus 1 (HIV-1)) |
| Volontari sani (Profilassi pre-esposione( PrEP) dell'virur 1 dell'immunodeficienza acquisita ( HIV-1) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Prevention of HIV |
| Prevenzione dell' HIV |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10073527 |
| E.1.2 | Term | HIV pre-exposure prophylaxis |
| E.1.2 | System Organ Class | 100000004865 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective of this study is:
-To assess the rates of HIV-1 infection in men (MSM) and transgender women (TGW) who have sex with men who are administered daily F/TAF or 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 primary objective of this study is:
-To assess the rates of HIV-1 infection in men (MSM) and transgender women (TGW) who have sex with men who are administered daily F/TAF or F/TDF with a minimum follow-up of 48 weeks and at least 50% of
subjects have 96 weeks of follow-up after randomization |
|
| E.2.2 | Secondary objectives of the trial |
- 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 participants 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 men (MSM) and transgender women (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 |
- 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 participants 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 men (MSM) and transgender women (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 |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Other types of substudies
Specify title, date and version of each substudy with relative objectives: A DXA substudy will be performed in a subset of approximately 400 subjects at a subset of sites (excluding Germany).
During the blinded phase of the study, all DXA substudy subjects will have scans at Day 1, Week 48, Week 96, and End of Blinded Treatment Phase visits. If continuing in the OL phase of the study, DXA substudy
subjects will have a scan at OL Week 48.
|
Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: A DXA substudy will be performed in a subset of approximately 400 subjects at a subset of sites (excluding Germany).
During the blinded phase of the study, all DXA substudy subjects will have scans at Day 1, Week 48, Week 96, and End of Blinded Treatment Phase visits. If continuing in the OL phase of the study, DXA substudy
subjects will have a scan at OL Week 48.
|
|
| E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
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 |
| Per i criteri di inclusione ed esclusione fare riferimento alla sezione 4 del protocollo |
|
| E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria are not to be
enrolled in this study.
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 or evidence of chronic hepatitis B infection.
Subjects found to be susceptible to HBV infection should be referred for
HBV vaccination
4) Evidence or known history of hepatitis C infection
5) Need for continued use of any contraindicated concomitant
medications
6) Have an implanted defibrillator or pacemaker
7) Have a history of osteoporosis or bone fragility fractures
8) Current alcohol or substance abuse judged by the Investigator to be
problematic such that it potentially interferes with subject study
compliance
9) Grade 3 or Grade 4 proteinuria or glycosuria that is unexplained or
not clinically manageable
10) 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
11) In the 30 days prior to screening have received F/TDF or any other
approved or investigational agent for the prevention of HIV-1 infection
or during the trial would be receiving any other approved or
investigational agents for the treatment/prevention of HIV-1 infection
12) Participation in any other clinical trial (including observational
trials) without prior approval from the sponsor is prohibited while
participating in this trial |
| Per i criteri di inclusione ed esclusione fare riferimento alla sezione 4 del protocollo |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint will be the incidence of HIV-1 infection per 100 PY when all subjects have a minimum follow-up of 48 weeks and at least 50% of the subjects have 96 weeks of follow-up after randomization.
HIV-1 infection is defined by one or more of the following criteria of contributing HIV tests performed via central lab or local lab:
1) Serologic evidence of seroconversion (reactive screening HIV Antigen/Antibody or Antibody test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated subjects, or
2) Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), or
3) Evidence of acute HIV-1 infection (reactive p24 Antigen or positive qualitative or quantitative RNA, in the absence of reactive HIV-1 Antibody results) |
The primary endpoint will be the incidence of HIV-1 infection per 100 PY when all subjects have a minimum follow-up of 48 weeks and at least 50% of the subjects have 96 weeks of follow-up after randomization.
HIV-1 infection is defined by one or more of the following criteria of contributing HIV tests performed via central lab or local lab:
1) Serologic evidence of seroconversion (reactive screening HIV Antigen/Antibody or Antibody test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated subjects, or
2) Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), or
3) Evidence of acute HIV-1 infection (reactive p24 Antigen or positive qualitative or quantitative RNA, in the absence of reactive HIV-1 Antibody results) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| When all subjects have a minimum follow-up of 48 weeks and at least 50% of the subjects have 96 weeks of follow-up after randomization |
| When all subjects have a minimum follow-up of 48 weeks and at least 50% of the subjects have 96 weeks of follow-up after randomization |
|
| E.5.2 | Secondary end point(s) |
The key (a-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
- The percent change from baseline in renal biomarkers of urine RBP to creatinine ratio, beta-2-microglobulin to creatinine ratio, and UPCR at Week 48
- The change from baseline in serum creatinine at Week 48 Other secondary endpoints include:
- The incidence of seroconversions per 100 PY as defined by the HIV
RNA-1 by PCR at the end of the blinded phase
- The percent change from baseline in hip and spine BMD at Week 96 in the blinded phase in a subset of subjects
- The percent change from baseline in renal biomarkers of urine RBP to creatinine ratio, urine beta-2-microglobulin to creatinine ratio, and UPCR at Week 96 in the blinded phase
- The change from baseline in serum creatinine at Week 96 in the blinded phase
- The incidence of treatment-emergent adverse events and laboratory toxicities; The key (a-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
- The percent change from baseline in renal biomarkers of urine RBP to creatinine ratio, beta-2-microglobulin to creatinine ratio, and UPCR at Week 48
- The change from baseline in serum creatinine at Week 48 Other secondary endpoints include:
- The incidence of seroconversions per 100 PY as defined by the HIV
RNA-1 by PCR at the end of the blinded phase
- The percent change from baseline in hip and spine BMD at Week 96 in the blinded phase in a subset of subjects
- The percent change from baseline in renal biomarkers of urine RBP to creatinine ratio, urine beta-2-microglobulin to creatinine ratio, and UPCR at Week 96 in the blinded phase
- The change from baseline in serum creatinine at Week 96 in the blinded phase
- The incidence of treatment-emergent adverse events and laboratory toxicities |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 48 and Week 96 |
| Settimana 48 e 96 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| United States |
| Austria |
| Denmark |
| France |
| Germany |
| Ireland |
| Netherlands |
| Spain |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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