Topic: Infectious diseases and microbiology
Conditions
Interventions
1. Blood borne virus screening: Blood sample-taking
2. Cervical biopsy: Tissue sampling
3. Cervico-vaginal examination: Colposcopy and Speculum examinations
Informed consent, To be taken by the study physician prior to starting study procedures
6. Medical history and physical exam: Conducted together, initially to establish eligibility, an
8. Randomisation: Participant to be assigned to one of the two trial arms, either Darunavir alone, or Dapivirine and Darunavir (randomisation is double-blinded)
9. Routine laboratory p
Sponsors
York Hospital NHS Trust
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Available for the duration of the study 2. Willing and able to give written informed consent 3. In good health as determined by medical history, physical examination, results of screening tests and the clinical judgment of a medically qualified investigator 4. Judged, in the opinion of a medically qualified investigator, to be able and likely to comply with all study requirements as set out in the protocol 5.Willing to undergo screening for HIV, Hepatitis B, Hepatitis C and sexually transmitted infections (Chlamydia, Gonorrhoea and Trichomonas) 6. Willing to abstain from vaginal practices including sexual intercourse and receptive oral sex from 48 hours before any given dose and up to 72 hours after 7. Willing to abstain from using any genital preparations other than the study gel during the period of gel administration and until the final follow up visit 8. Willing to abstain from using tampons during the two periods of gel administration 9. Willing to refrain from blood donation for the duration of the study 10. If fertile, using a reliable method of contraception for the 3 to 4 menstrual cycles covering the cycles pre study, during study dosing and until the final follow up visit has been completed. For the purposes of this trial only the following will be accepted as a reliable form of contraception: 10.1. Consistent use of condoms with every act of sexual intercourse 10.2. Combined oral contraceptive pill 10.3. Desogestrel containing progesterone only pill (Cerazette) 10.4. Intrauterine contraceptive device or system 10.5. Injectable contraceptive or progesterone implant 11. Willing to undergo a urinary pregnancy test at screening, on the day of randomisation, on the day of receipt of the second dose of the microbicide and at the final follow up visit 12. Have been registered with a General Practitioner (GP) for at least the past 3 months and willing to allow the investigators to discuss the volunteer’s medical history with their GP prior to randomisation 13. Agree to registration on a national database of trial subjects to prevent overvolunteering (TOPS), and to the taking of a photograph to be kept at the trial site 14. Upper Age Limit 50 years ; Lower Age Limit 18 years
Exclusion criteria
Exclusion criteria: Untreated syphilis, gonorrhoea, trichomonas, chlamydia, vaginal candidosis or bacterial vaginosis (participants who test positive for any of these infections and are subsequently treated will be eligible provided all other inclusion criteria are met) 1. Seropositive for hepatitis B surface antigen (HBsAg) or Hepatitis C (antibodies to HCV) or HIV 2. Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis 3. Abnormal findings on pelvic examination, deemed clinically significant by a medically qualified investigator 4. Irregular menstrual bleeding likely to cause vaginal bleeding during the dosing period as judged by a medically qualified investigator 5. Treatment for CIN or other gynaecological instrumentation of the cervix within the last 3 months 6. An allergy to parabens or any of the other IMP constituents 7. Insertion of an intrauterine contraceptive device or system within the last 6 weeks 8. Any other significant disease, disorder or finding, which, in the opinion of a medically qualified investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer’s ability to participate in the study 9. Participation in another research study involving an investigational product in the 3 months preceding enrollment, or planned use during the study period 10. Pregnant, less than 12 weeks postpartum, lactating or willingness/intention to become pregnant during the study 11. Significant concern raised by GP in relation to participation 12. Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required inparticipation and consent 13. Unlikely to comply with the study protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Concentrations of IMP in secretions, plasma and tissue; Timepoint(s): 8 and 24 hours after a single dose, 12 and 36 hours after 14 doses | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Anti-HIV activity in cervico-vaginal secretions using the Tibotec MT4-GFP assay; Timepoint(s): 8 and 24 hours after a single dose, 12 and 36 hours after 14 doses 2. Correlations of Dapivirine and Darunavir levels with anti-HIV activity; Timepoint(s): 8 and 24 hours after a single dose, 12 and 36 hours after 14 doses 3. Number of events attributable to the study gel leading to discontinuation of the gel; Timepoint(s): At any time during the single or multiple dosing periods 4. Number of grade 3 or above clinical or laboratory AEs confirmed; Timepoint(s): At examination or on repeat testing respectively during the dosing or at examination 5. Number of grade 3 or above genital adverse events (AEs); Timepoint(s): During the dosing or follow up period 6. Prevalence of six respective types of vaginal flora; Timepoint(s): pre-dosing, post-single and post-multiple dosing 7. Vaginal slide Nugent scores; Timepoint(s): pre-dosing, post-single and post-multiple dosing | — |
Countries
United Kingdom
Outcome results
None listed