Study to Evaluate the Safety and Efficacy of Emtricitabine and Tenofovir Alafenamide (F/TAF) Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis in Men and Transgender Women Who Have Sex With Men and Are At Risk of HIV-1 Infection

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

13 Dec 2016 → ongoing

Decision date (initial)

2023-06-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Gilead Sciences Inc.

External identifiers

EU CT number

2022-501763-40-00

EudraCT number

2016-001399-31

ClinicalTrials.gov

NCT02842086

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Safety, Efficacy, Pharmacokinetic

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 F/TAF or F/TDF with a minimum follow up of 48 weeks and at least 50% of participants have 96 weeks of follow up after randomization

Secondary objectives 4

1. To compare bone safety between the treatments as determined by dual-energy X-ray absorptiometry (DXA) tests of hip and spine BMD in a subset of participants at Week 48 and Week 96 in the blinded phase
2. 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
3. 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 participants have 96 weeks of follow up after randomization
4. To compare the general safety between the treatments

Conditions and MedDRA coding

Pre-Exposure Prophylaxis of HIV-1 Infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 2 unique male partners in the past 12 weeks (partners must be either PWH 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 glomerular filtration rate (eGFR) ≥ 60 mL/min according to the Cockcroft-Gault formula for creatinine clearance {Cockcroft 1976}: (140 ― age in years) × (wt in kg) / 72 × (serum creatinine in mg/dL) = CLcr(mL/min)
5. Adequate liver and hematologic function: • AST and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); and total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin • Absolute neutrophil count ≥ 1000/mm3, platelets ≥ 75,000/mm3, and hemoglobin ≥ 10 g/dL
6. Willing and able to comply with study procedures

Exclusion criteria 11

1. Known hypersensitivity to the study drug, 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. Participants found to be susceptible to hepatitis B virus (HBV) infection should be referred for HBV vaccination. Participants found to be positive for hepatitis C virus (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 participant 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 participant 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 study (including observational studies) without prior approval from the sponsor is prohibited while participating in this study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. The primary endpoint will be the incidence of HIV-1 infection per 100 person years (PY) when all participants have a minimum follow up of 48 weeks and at least 50% of the participants have 96 weeks of follow up after randomization. HIV-1 infection is defined by 1 or more of the following criteria of contributing HIV tests performed via central lab or local lab:
2. Serologic evidence of seroconversion (reactive screening HIV antigen [Ag]/antibody [Ab] or Ab test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated participants, or
3. Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), or
4. Evidence of acute HIV-1 infection (reactive p24 Ag or positive qualitative or quantitative RNA, in the absence of a reactive HIV-1 Ab test results)

Secondary endpoints 15

1. The percent change from baseline in hip BMD at Week 48 in a subset of participants
2. The percent change from baseline in spine BMD at Week 48 in a subset of participants
3. Assessment of renal biomarkers at Week 48
4. Percent change from baseline in urine beta-2-microglobulin to creatinine ratio
5. Percent change from baseline in urine RBP to creatinine ratio
6. Distribution of UP and UPCR categories
7. The change from baseline in serum creatinine at Week 48
8. The incidence of HIV-1 infection (as per Appendix 11.6) per 100 PY when all participants have 96 weeks of follow up after randomization
9. The percent change from baseline in hip and spine BMD at Week 96 in the blinded phase in a subset of participants
10. Assessment of renal biomarkers at Week 96 in the blinded phase
11. Percent change from baseline in urine beta-2-microglobulin to creatinine ratio
12. Percent change from baseline in urine RBP to creatinine ratio
13. Distribution of UP and UPCR categories
14. The change from baseline in serum creatinine at Week 96 in the blinded phase
15. The incidence of treatment-emergent adverse events (AEs) and laboratory toxicities

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU Clinical Trials Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU Clinical Trials Support

Third parties 6

Locations

7 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 49 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications