E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Viruses |
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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 | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
E.1.2 | Term | Infections and infestations |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
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
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Non-infection of vaginal and rectal tissue with HIV (in the lab) at 15 days following ex vivo challenge.
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E.5.1.1 | 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 |
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E.5.2 | 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.
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E.5.2.1 | 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 |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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Data lock. Data lock will be defined as all participant clinical visit data, laboratory data and qualitative data being obtained and cleaned in preparation for transfer to statistician. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |