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)) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
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 |
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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 seroconversion 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 |
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E.2.2 | Secondary objectives of the trial |
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 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 seroconversion in men (MSM) and transgender women (TGW) who have sex with men who are administered daily F/TAF or F/TDF at the end of blinded phase
- To compare the general safety between the treatments
Further exploratory endpoints are included as per the protocol. |
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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 |
- 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 substudy subjects will have DXA scan of the hip and spine at Day 1, Week 48 and Week 96. Substudy subjects in Treatment Arm 2 (F/TDF) will have an additional scan at the Unblinding Visit which will serve as a baseline for the open-label phase. All substudy subjects will have a scan at OL Week 48. |
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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 |
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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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the incidence of seroconversions per 100 PY as defined by the HIV-1 RNA by PCR when the last subject has a minimum of 48 weeks of follow-up and 50% of the subjects have at least 96 weeks of follow-up after randomization. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
When the last subject has a minimum of 48 weeks of follow-up and 50% of the subjects have at least 96 weeks of follow-up after randomization |
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E.5.2 | Secondary end point(s) |
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
- 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | Yes |
E.8.2.2 | Placebo | No |
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 | 4 |
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 | No |
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 |
Austria |
Canada |
Denmark |
France |
Germany |
Ireland |
Netherlands |
Spain |
United Kingdom |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |