Human Immunodeficiency Viruses MedDRA version: 20.0 Level: SOC Classification code 10021881 Term: Infections and infestations System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Descovy 200 / 25 mg
Product Name: Descovy 200 / 25 mg
Product Code: J05AR17
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Emtricitabine
CAS Number: 143491-57-0
Concentrati
Sponsors
Guy's & St. Thomas' NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The ability to understand and sign a written informed consent form prior to participation in any screening procedures and must be willing to comply with all trial requirements. 2. Male or non-pregnant, non-lactating females 3. Age between 18 to 60 years, inclusive. 4. Weight above 35kg. 5. Negative antibody/antigen combined test for HIV. 6. Women of childbearing potential (WOCBP)( i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause) who are participating in sexual intercourse that could result in pregnancy, must be using highly effective contraception throughout the study and for two weeks after the study. This includes intrauterine device, , anatomical sterility in self or partner, oral hormonal methods, and implant contraceptives. In case of anatomical sterility in a partner, for example vasectomy, it will be considered a highly effective birth control method provided that the partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success 7. Female participants who consent not use any vaginal products or objects or have vaginal sex for 48 hours before and after the collection of vaginal fluid and vaginal biopsies. This list includes tampons, female condoms, cotton wool, rags, diaphragms, cervical caps (or any other vaginal barrier method),douches, lubricants, vibrators/dildos, and drying agents. 8. Males participating in sexual intercourse that could result in pregnancy who consent to use condoms during the duration of the study. 9. Men and women who consent not to use anal products or objects including but not exclusive to douches, lubricants and vibrators/dildos, butt plugs or urethral sounds or have receptive anal intercourse for 48 hours before and after the collection of rectal biopsies. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 84 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Any significant acute or chronic medical illness as determined by the investigator. 2. Evidence of organ dysfunction or any clinically significant abnormality in physical examination, vital signs or clinical laboratory determinations. 3. Positive blood screen for syphilis (RPR), hepatitis B (HBsAg) and/or C antibodies. 4. Positive blood screen for HIV antibodies 5. Positive screen for sexually transmitted infections at screening visit 6. High-risk behaviour for HIV infection, which is defined as having one of the following within three months before trial day 0 (first dose): i. had condomless vaginal or anal sex with a known HIV-1 infected person who is not receiving ART, or a casual partner. ii. engaged in sex work for money or drugs. iii. acquired a bacterial sexually transmitted disease. 7. Females who are pregnant or breast-feeding. 8. Clinically significant laboratory abnormalities as determined by an investigator. 9. Participation in a clinical trial of an Investigational product within 1 month of planned baseline enrolment and for the duration of the trial. 10. Receiving any of the following medications; carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, St. John's wort, ketoconazole, itraconazole, fluconazole, Isavuconazole and ciclosporin. 11. Hypersensitivity to the IMPs active substances or to any of the excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For each drug (Truvada and Descovy) we have the following objectives: Part 1: 1.To determine the level of drug required in the plasma, saliva, vagina and rectum for ex vivo protection from HIV-1 Part 2: 1. To determine the minimal dosing requirement for on demand PreP ;Secondary Objective: For each drug (Truvada and Descovy) we have the following objectives: Part 1: 1. To determine the time from first dose of drug to ex vivo protection from HIV-1 infection 2. To determine the time to cessation of ex vivo protection from HIV-1 following stopping ART after attaining steady state. 3. To determine the impact of TRUVADA® and DESCOVY® on the genital microbiome in men and women 4. To determine the relationship between protection from ex vivo infection in tissue and Peripheral Blood Mononuclear Cells (PBMC) 5. To investigate PrEP acceptability and feedback on the trial implementation Part 2: 1. To determine the level of drug required in the plasma, saliva, vagina and rectum for ex vivo protection from HIV-1 2. To determine the optimal time from PrEP dosing to HIV exposure 3. To determine the contribution of post exposure dosing in on-demand PrEP 4. To investigate PrEP acceptability and feedback on the trial implementation ;Primary end point(s): Non-infection of vaginal and rectal tissue with HIV (in the lab) at 15 days following ex vivo challenge. ;Timepoint(s) of evaluation of this end point: Part 1 Regime 1: Biopsy on treatment:day 4,7 or 21 Biopsy off treatment: day 29,31 or 33 Part 1 Regime 2: Biopsy on treatment:day 65,69 or 73 Biopsy off treatment: day 90,92 or 93 Part 2 Biopsy on and off treatment:day 4,7 or 21 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The mean p24 antigen level area under the curve (AUC) and p24 antigen slope from day 3 to day 15 b. Drug levels in plasma (TFV, FTC, TAF), peripheral blood mononuclear cells CD4 T cells (TFV-DP and FTC-TP), saliva, vaginal and rectal fluid following PrEP initiation and after cessation. ;Timepoint(s) of evaluation of this end point: Part 1 Regime 1: On treatment:Samples at day 4,7 or 21 Off treatment: Samples at day 29,31 or 33 Part 1 Regime 2: On treatment: Samples at day 4,7 or 21 Off treatment: Samples at day 29,30 or 33 Part 2 On and off treatment: Samples at day 4,7 or 21 | — |
Countries
United Kingdom
Contacts
Public ContactDr Julie Fox
Guys and St Thomas’ NHS Foundation Trust
Outcome results
None listed