José Bauermeister PhD, MPH University of Pennsylvania MTN BRWG Member Building and testing rectal microbicide products: Creating a new era of RM research and development José Bauermeister PhD, MPH University of Pennsylvania MTN BRWG Member

From hypothetical to reality Approximating Real-Life Behaviors within the Procedures of a Clinical Trial Study

Modality Scorecard Liu. 2017 Annual MTN Meeting

Choice matters… PrEP may not be accessible, available or desired among population segments. Adherence challenges Access & Cost Topical prophylaxis may have buy-in among vulnerable populations who experience risk seasonally.

Research within Clinical Trial Models Behavioral assessments are often interwoven within RM safety studies. Expectation that behavioral adherence strategies will be effective. Plug-and-Play Interventions within Biomedical Trials Different products require different strategies

What we have asked…. Awareness Use/Adherence Acceptability Do they know about the product? Use/Adherence Did they use the product? Acceptability What predicts product use and intention? Non-Use Predictors What predicts non-use?

Cherchez Le Creneau Traditional Approach Positioning Approach Product is Developed in Isolation Product is Given to Customers Ignore competition Highlight benefits Expect high adoption and adherence Positioning Approach Understand consumers’ values Product is developed with consumer in mind Understand competition Relate product to existing brands Retie users’ experiences with other products to our product.

Lin AH, Breger TL, Barnhart M, Kim A, Vangsgaard C, Harris E Lin AH, Breger TL, Barnhart M, Kim A, Vangsgaard C, Harris E. Learning from the private sector: towards a keener understanding of the end-user for microbicide introduction planning. J Int AIDS Soc. 2014;17(3(Suppl 2). doi:10.7448/IAS.17.3.19162.

Gel-based RM Rectal Microbicide R&D has prioritized gel-based formulations. Gel often noted as preferred formulation method by participants, yet current delivery approach has challenges.

MTN-026 MTN-026/IPM 038 is the first clinical trial to collect safety and pharmacokinetic data on the rectal application of dapivirine gel (0.05%) in a cohort of HIV-uninfected adults. Behavioral Data: User acceptability of the product User-centered suggestions for product design and delivery Satisfaction with the clinical trial experience Suggestions to improve the trials from a user perspective

MTN-037 MTN-037 is a Phase 1, open label, sequential dose/VET designed to evaluate the safety and PK of PC-1005 (MIV-150/Zinc Acetate/Carrageenan gel) when administered rectally in men.  Different Volumes : Acceptability & Tolerability of the product User-centered suggestions for product design and delivery Satisfaction with the clinical trial experience Suggestions to improve the trials from a user perspective

Modality & Delivery Matters…. Carballo-Dieguez et al., 2014. AIDS & Behavior Bauermeister et al., 2016. AIDS Ed. & Prev.

MTN-033 MTN-033/IPM 044 is one of the first clinical trials involving the rectal application of dapivirine gel (0.05%) in a cohort of HIV-uninfected adults. Assess study gel safety and acceptability, including comparison between Applicator and Self-Administration: User perceptibility Existing product use and satisfaction/needs User-centered suggestions for product design Experiences with the direct observation dosage method

Beyond gel: Diverse modalities… MSM/TW often report using other rectal products before/after sex. Diverse modalities may accommodate different social/structural circumstances. Different segments of the population may prefer some modalities over others.

Preferred Modality may vary… All cities (N=128) Lima (N=32) Iquitos (N=31) Guayaquil (N=33) Rio (N=32) Cost ($) Effect. (%) Side Effects Frequency of use Form. Dose (ml) Rx or OTC 1 87.30 (23.96) 83.06 (26.31) 83.06 (26.92) 92.19 (19.51) 90.83 (20.22) .30 80 None Before sex Gel 15 Rx 2 60.77 (33.74) 65.83 (33.40) 62.90 (33.46) 50.00 (34.78) 53.33 (35.19) 5 Some 35 OTC 3 58.54 (34.60) 54.03 (33.60) 41.13 (34.49) 60.94 (33.56) 59.48 (34.34) Daily Liquid Consumer Psychology

Rectal Douching Before RAI After RAI Desire to maintain personal hygiene Request by sexual partner Douching enhances pleasure Friends discussed douching before sex Desire to prepare/get excited for RAI After RAI Protection from STI’s Desire to maintain personal hygiene Desire to transition from sex Request by sexual partner Douching enhances pleasure Friends discussed douching after sex

Insert/Suppository Limited data on acceptability, tolerability and adherence of suppository vs. insert modality. Carballo-Dieguez (2008) found that MSM preferred gel microbicides over a suppository. However, the suppository used was larger than would be needed for RM delivery. Studies are needed to assess acceptability of a smaller/differently shaped and formulated.

MTN-039 Safety and PK Study of TDF and EVG Administered Rectally Inserts: User acceptability of the product User-centered suggestions for product design and delivery Satisfaction with the clinical trial experience Suggestions to improve the trials from a user perspective

MTN 035 First study to systematically examine the acceptability, tolerability and adherence of three placebo formulations in a sample of young MSM/TP in 5 countries. Describe usage patterns and the correlates linked to trajectories of use. Compare/contrast modalities based on product characteristics and participants’ characteristics and contexts. Assess modality acceptability and tolerability, including best practices learned from participants’ experiences, as MTN explores formulations.

Washout period (~1 week) MTN 035 Sequence N Period 1 (4 weeks) Washout period (~1 week) Period 2 Period 3 A 35 Rectal insert -- Rectal douche Rectal suppository B C D E F

Flipping the script… Traditional Research Awareness Tolerability Acceptability Adherence Sustainability Design-driven Research How can we understand participants’ contexts better? How do we get them to desire our product? What makes people keep wanting to use our product? How do we make a product that is easy and vital to way of life?

The way forward!

Acknowledgements The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. The content is solely the responsibility of the author and does not necessarily represent the official views of funding agencies.