The objective of this FOA is to support development of novel long-acting, systemic and non-systemic and on-demand and event-driven Multipurpose Prevention Technologies (MPTs) for the purposes of pregnancy and STI or HIV infection prevention and prevention of multiple non-HIV STI or HIV/STI MPTs in cis and trans males and females of all ages, as appropriate. Of specific interest to general MPT development are efforts focused on specific sub-populations where MPTs may have a particular benefit such as, adolescent girls, women and men in serodiscordant partnerships, men who have sex with men (MSM), individuals who practice receptive anal intercourse (RAI) or engage in high-risk sexual encounters, health disparity populations that are disproportionately infected by HIV or other STIs, and individuals who may desire the convenience of a multi-component prevention strategy.
MPTs are composed of a combination of drugs that can target prevention of pregnancy, STIs (e.g. Gonorrhea, Syphilis, Chlamydia, Trichomonas vaginalis, Human Papilloma Virus (HPV), Herpes Virus (HSV), etc.) and/or HIV delivered using either an on-demand and event-driven or long-acting drug delivery system (DDS) with rheological/biophysical properties and product user perceptions (look, feel, effectiveness, safety and duration of action) that support user uptake (first use, subsequent use and habitual use). The hypothetical power of the MPT concept is that by combining prevention products for pregnancy and HIV or STI, prevention products for HIV and STIs or agents to prevent multiple non-HIV STIs into a single product, the MPT may have a greater uptake and adherence by at-risk individuals than individual products. Key to the concept of MPTs is creation of DDS to support convenience of use, that not only are safe and deliver the drugs consistently but have durations of action relevant to the user needs. MPTs (contraceptive and non-contraceptive) may encompass a wide range of delivery durations and use patterns from on demand, event-driven or sustained/extended release durations (months to years), while non-contraceptive MPTs may be modeled for use around sexual activity or for longer durations of protection.
MPTs in general represent an unmet need for both cis and trans males and females. The first generation of contraceptive/HIV MPTs using a drug development strategy focused on adapting the contraceptive hormone Levonorgestrel (LNG) to intravaginal rings (IVR) containing Tenofovir or Dapivirine are undergoing initial clinical testing, whereas development of HIV/STI, contraceptive/STI and non-HIV STI MPTs are either in preclinical development or have yet to be conceived. Creation of MPTs with a range of STI prevention, contraception and anti-HIV drug choices that are convenient and retain the efficacy/safety of single component drugs will be a critical factor in getting individuals to choose an MPT, since it is unlikely that reduced efficacy and/or convenience will entice substitution of an MPT for a more familiar and/or trusted single drug treatment/prevention regimen. Thus, close attention to pharmacokinetics (PK)/ pharmacodynamics (PD) of the constituents of the MPT and biophysical properties of the DDS, as they pertain to user preferences and needs, are essential components required for creating new, effective strategies that are purpose designed to meet the needs of at-risk individuals and those desirous of a multi-component prevention strategy.
Applicants are encouraged to consider specifying clinical and nonclinical research milestones and timelines for their proposed research. Inclusion of biobehavioral research, integrated into an MPT drug development program, focused on optimizing the rheological and biophysical properties of the product for use by target populations is encouraged. Applications may address one or more of the following interest topics.
- Development of episodic dosed MPTs for use during periods of sexual activity with a minimum of 7 days protection from a single dose for MPTs targeting HIV and STIs for cis and trans males and females.
- Development of sustained/extended release MPTs that provide months to years of protection from HIV and/or STI infection and pregnancy in women using a single dose or a constant delivery DDS, which may be modeled after the highly effective long-acting reversible contraceptive (LARC) strategies for durations and use patterns.
- Development of animal models (single model or separate harmonized animal models) that evaluate the efficacy and safety for the active ingredients of a multiple indication MPT product.
- Understanding the potential for and identifying/characterizing DDI that could compromise MPT safety and effectiveness.
- Understanding the PK and PD of MPT products by mapping the antiviral, STI(s) and/or contraceptive duration, lag period (time to establish effective concentrations) and tails (time to loss of effective concentrations) during non-use periods such as menstruation or between dose renewals for episodic and sustained/extended release MPTs.
- Development of contraceptive and non-contraceptive MPTs that deliver effective HIV drug concentrations to both the female reproductive tract (FRT) and the gastrointestinal (GI) tract of males and females.
- Understanding the biobehavioral factors which govern decisions made by individuals to use MPTs (look, feel and duration). For this FOA, biobehavioral factors are defined as the rheological/biophysical properties of the MPT DDS that invoke user judgments, leading to decisions for first, subsequent use or non-use and/or early termination.
- Studies that integrate a meaningful behavioral component addressing preferred user characteristics into a proposed product development plan.
- Studies to understand which products and delivery systems are preferred by whom.
- Studies to understand how partner and situational/contextual factors influence product preferences.
- Research designed to inform the development of MPT products by investigating relevant healthcare system delivery factors regarding dosing schedules and administration routes.
- Research to identify product attributes and other behavioral, social, and healthcare system determinants that may affect consumer adherence to MPT products.
- Studies examining whether MPT formulations may improve product adherence and persistence relative to products that prevent only HIV.
- Studies that model the cost-effectiveness of MPT products.
NICHD. NICHD’s Maternal and Pediatric Infectious Disease Branch (MPIDB) is particularly interested in efforts targeting infants, children, adolescents and young adults and/or pregnant women.
- Development of MPT formulations, systemic and non-systemic, for HIV, STIs and/or pregnancy prevention in formulations and/or drug platforms that are appropriate for administration to adolescent and young adults, particularly formulations that do not require a cold chain, are not liquids with solid and are palatable (e.g. incorporating effective taste masking technologies)
- Evaluation of STI/STI and STI/HIV MPT formulations in pregnant animals, including toxicity studies for mother/fetus as well as assessments for teratogenicity.
- Studies involving the investigation of pharmacologic properties of proposed formulations in animal models to understand the interaction of the formulation with endocrine, physiologic and other biochemical changes experienced among, adolescent and young adult populations (e.g. effects on reproductive organs, growth, changes in volume of distribution [e.g. due to potential portioning in fat], hormonal effects, potential for unique toxicities [e.g. bone, CNS]).
- Studies to evaluate key pharmacologic interactions of MPT formulations with agents commonly used by and behaviors typically practiced among adolescent and young adult populations (e.g. contraceptives, alcohol, smoking, illicit substances, erratic eating behaviors).
NICHD’s Contraception Research Branch (CRB) is particularly interested in the development of new and improved methods of contraception, including multipurpose prevention technologies which include a contraceptive component.
- Development of novel non-hormonal MPTs and MPT delivery systems, either on-demand and event-driven or sustained release, in men or women with pregnancy prevention and HIV and/or STI properties.
- Development of on-demand and event-driven dosed MPTs for use during periods of sexual activity with a minimum of 2 days protection from a single dose for MPTs targeting pregnancy prevention and HIV and/or STIs for men and women.
- Development of sustained/extended release MPTs that provide months to years of protection from pregnancy and HIV and/or STI in women using a single dose or a constant delivery DDS.
- Understanding the PK and PD of MPT products by mapping the contraceptive, antiviral and/or STI duration, lag period (time to establish effective concentrations) and tails (time to loss of effective concentrations) during non-use periods such as menstruation or between dose renewals for on-demand and event-driven and sustained/extended release MPTs.
- Understanding the potential for and identifying/characterizing DDI that could compromise a pregnancy prevention and HIV and/or STI MPT safety and effectiveness.
Special Note: Consultation with NICHD staff prior to submission of an application is strongly encouraged.
Note: The areas below are areas NOT being sought through this FOA.
- Applications that propose developing a product with a single indication/target organism or do not propose to develop an MPT, as defined above.
- Clinical trials (Phase I, II or III and exploratory IND) proposing dosing of an MPT already in development or proposed for development in the application.
- MPT strategies composed of HIV or STI vaccines.
- Use of live biotherapeutics or vectored biotherapeutics to deliver the anti-HIV component(s) of an MPT.
Deadlines: May 6, 2019; May 6, 2020; May 6, 2021 (letters of intent due 30 days prior to deadline)
Filed Under: Funding Opportunities