- To compare the local and systemic pharmacokinetics (PK) of two extended duration dapivirine (DPV) vaginal rings (VRs) (100 mg and 200 mg) used continuously for 13 weeks to the current 25 mg DPV VR when replaced every 4 weeks for 8 weeks and then worn for an additional five weeks for a total of 13 weeks)
- To compare the safety of the two-extended duration DPV VRs (100 mg and 200 mg) to the current 25 mg DPV VR when used for 13 weeks
MTN-036/IPM 047 was a Phase 1, three-arm, multi-site, randomized (1:1:1) trial designed to collect data on the PK and safety profile of DPV when administered via silicone elastomer VR containing the active ingredient at three dosage strengths: 25 mg DPV (IPM Ring-004) [Comparator VR]), 100 mg DPV (IPM Ring-008) and 200 mg DPV (IPM Ring-006). Forty-nine healthy, HIV-uninfected, non-pregnant women between 18-45 years of age were enrolled in the study and followed for approximately 97 days. Participants inserted one VR to be used continuously for 90 days (100 mg and 200 mg VRs) or replaced monthly for 3 months (25 mg VR). MTN-036/IPM 047 collected local and systemic pharmacokinetic data as well as safety information on the vaginal rings. The study also investigated the acceptability of and adherence to the VRs and explore changes in vaginal microflora and biomarkers over 90 days of product use. It is hypothesized that plasma, cervicovaginal fluid and cervical tissue DPV levels will be measurable in all women randomized to DPV VRs, that continuous exposure to DPV due to sustained release from the 100 mg and 200 mg VRs for 13 weeks will be safe, and that dose-proportionality will be demonstrated in tissue and systemic PK.
The study completed follow-up on January 23, 2019. Primary results were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) held virtually on March 6-10, 2021. The primary manuscript was published online in Journal of the International AIDS Society in June 2021. A total of three papers have been published from this study.
There were no differences in the proportion of participants with grade ≥2 genitourinary AEs or grade ≥3 AEs in the extended duration versus monthly ring arms (p = 1.0). Plasma and CVF DPV concentrations were higher in the extended duration rings compared to the monthly ring. Plasma GMRs were 1.31 to 1.85 and 1.41 to 1.86 and CVF GMRs were 1.45 to 2.87 and 1.74 to 2.60 for the 100 and 200 mg ring respectively. Cervical tissue concentrations were consistently higher in the 200 mg ring (GMRs 2.36 to 3.97). The majority of participants (82%) were fully adherent (ring inserted at all times, with no product discontinuations/outages) with no differences between the monthly versus three-month rings. Most participants found the ring acceptable (median = 8 on 10-point Likert scale), with a greater proportion of participants reporting high acceptability (9 or 10) in the 25 mg arm (73%) compared with the 100 mg (25%) and 200 mg (44%) arms (p = 0.01 and p = 0.15 respectively). The extended duration DPV rings were well-tolerated and achieved higher DPV concentrations compared with the monthly DPV ring. These findings support further evaluation of three-month DPV rings for HIV prevention.
US Eunice Kennedy Shriver National Institute of Child Health and Human Development
US National Institute of Mental Health
US National Institutes of Health
Phase 1, three-arm, randomized (1:1:1), open-label trial