Phase 1 Clinical Trial for Therapeutic Intervention Particles (TIPs)
Abstract
Current therapeutic approaches continue to face enormous challenges in containing infectious diseases such as HIV/AIDS; in 2019, 31,000 U.S. military Veterans were living with HIV, 1.7 million people acquired HIV worldwide, and HIV prevalence was >30% in many parts of sub-Saharan Africa—despite billions of dollars spent on continent-wide drug-therapy campaigns. Three universal barriers render current interventions ineffective: (i) Pathogens mutate; current therapies do not. (ii) Infection is often lifelong; patients in resource-limited settings often cannot maintain lifelong adherence and discontinue therapy in <2 years. (iii) Interventions rarely reach the highest-risk groups (e.g., commercial sex workers and injecting drug users) who drive the overwhelming majority of disease spread. A vaccine will face many of the same barriers. Supported by funding from the Department of Defense, we proposed and engineered a new class of antiviral medicine that overcomes these universal barriers to infectious disease control. These novel antiviral medicines—called Therapeutic Interfering Particles, or TIPs—act as “molecular parasites” of HIV, inhibit the virus, and self-renew in HIV-infected individuals, thus acting as single-administration (i.e., one-time) therapies to circumvent adherence and compliance issues. TIPs have the unique capacity to reach the highest-risk groups who most need therapy. Laboratory models shows that TIPs have the capacity to be “resistance-proof,” and epidemiological analyses show they would surmount the universal barriers and drive HIV/AIDS prevalence to below 1% in sub-Saharan Africa, far below the levels achievable by vaccination or antiretroviral campaigns. Preclinical studies showed that TIPs inhibit HIV and protect human cells from HIV infection in humanized mice. Based on these promising animal data—and initial evaluation by the U.S. Food and Drug Administration (FDA)—the aims of this proposed project are to evaluate the safety of TIPs in a first-in-human clinical trial in HIV-infected patients. Existing data in mice indicate that TIPs begin to reduce HIV levels and protect human cells within five weeks of administration. The FY20 focus area addressed by this project is the Military Infectious Disease Research Program. The military benefits of this work pertain to military Veterans; the U.S. Department of Veterans Affairs (VA) is the largest single provider of HIV-1 care in the U.S., caring for approximately 31,000 HIV-infected Veterans (1 in 250 Veterans living with HIV as of 2019). The annual cost of an HIV antiretroviral drug regimen for a single infected individual has risen to $31,000–$48,000 per year (despite the availability of generics) and the overall costs of providing lifelong continuous antiviral therapy to the HIV-infected population are projected to increase to ~$31 billion/year before 2030. A single-administration, resistance-proof therapeutic for HIV-1 would substantially improve the quality of life for infected Veterans and their caregivers, both of whom often face additional adversities that complicate and limit access to continuous care. Ultimately, a “one-time” therapy such as TIPs could also significantly reduce incidence of new HIV infections in the U.S., thereby generating a significant public-health improvement for the American public. The contribution of this study will be the first-in-human demonstration of safety of TIPs. This safety trial represents the first regulatory step required to translate a novel laboratory prototype into medical countermeasure for the clinic and will be completed within a 3-year timeframe leading to Phase II clinical trials. Demonstration of TIP safety in humans will accelerate buy-in of other government clinical trial sponsors (e.g., NIH, BARDA), industry stakeholders, and non-governmental organizations to fund the next stage of clinical trials. Based on existing clinical-trial precedents and FDA timelines, if Phase I safety is demons
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110875
Entities
People
- Leor S Weinberger
Organizations
- The J. David Gladstone Institutes
- United States Army