OBJECTIVES/GOALS: This study aimed to characterize urinary exosomal miRNA content in African American adults with diabetic kidney disease. METHODS/STUDY POPULATION: Male and female participants between the ages of 18 and 65 were recruited from the Diabetes Treatment Center and the Nephrology Clinic at the Howard University Hospital. Exosomes were isolated from cleared urine of healthy controls (n=3), type 2 diabetics (n=3), and participants with chronic kidney disease (n=3). The purity and size of isolated microparticles was evaluated using NanoSight technology (30nm to 120nm size range) and western blot analysis for exosome-specific markers (TSG101 and CD81) RESULTS/ANTICIPATED RESULTS: Expression of 5 selected microRNAs, miR-4534, miR-320c, miR-451, miR-362-3p and miR-877-3p were evaluated by qRT-PCR. miR-4534 and miR-451 was increased between healthy controls and the type diabetic group. MiR-320c was increased in the CKD group, in comparison to healthy controls. Conversely, there was no difference in miR-877-5p between the three groups. DISCUSSION/SIGNIFICANCE: These findings will provide insight into the use of circulating miRNAs as early markers of DKD, ultimately creating more effective treatments and preventive measures.

OBJECTIVES/GOALS: The research objectives of this project are to elucidate the effects of Bruton’s tyrosine kinase inhibitors (BTKi) of varying target specificity on platelet function with regard to platelet aggregation, adhesion, spreading, and intracellular signaling as measured by kinase phosphorylation. METHODS/STUDY POPULATION: Blood from healthy volunteers was obtained and processed to obtain both washed platelets and platelet-rich plasma. The samples were then treated with one of the BTKi drugs or with vehicle (DMSO) at concentrations matching patient blood concentrations derived from clinical trials and pharmacokinetic studies. The incubated samples were then analyzed in an aggregometer using one of several agonists. Aggregation was stopped after five minutes with a perchloric acid-based lysis buffer. The samples were then analyzed by SDS-PAGE and immunoblotting to quantify BTK protein and BTK phosphorylation. Adhesion was assessed by incubating washed platelets treated with BTKi on microtiter wells coated with fibrinogen or collagen and quantifying adherent platelets by their endogenous acid phosphatase activity. RESULTS/ANTICIPATED RESULTS: We found that ibrutinib, zanubrutinib, and pirtobrutinib all completely inhibited collagen-induced platelet aggregation, whereas they did not inhibit aggregation induced by thrombin, ristocetin, arachidonic acid, or the PAR1 activator peptide SFLLRN (T6). Acalabrutinib inhibited collagen-induced platelet aggregation only at high concentrations (1-2 micromolar). At the lower concentration of 200 nanomolar, comparable to the concentration required for the other BTK inhibitors to completely inhibit platelet aggregation, acalabrutinib failed to inhibit aggregation but did inhibit auto-phosphorylation, indicating an impact on signaling. None of the BTKi drugs inhibited adhesion of platelets to collagen-coated surfaces. DISCUSSION/SIGNIFICANCE: Our data show the inhibitory effect of BTKi on collagen-induced platelet aggregation and signaling. However, it remains unclear whether the inhibition is due to an effect on BTK itself or other related kinases. Better insight into the mechanisms of platelet inhibition by BTKi may help guide the development of BTKi with a lower risk of hemorrhage.

OBJECTIVES/GOALS: Chronic kidney disease (CKD) impacts 15% of US adults and African American (AA) persons are disproportionately affected with more than 3 times higher risk of kidney failure when compared to Caucasian persons. This study evaluated the physiological and metabolomic effects of increased fruits and vegetables (F&V) on cardio-renal risk factors. METHODS/STUDY POPULATION: This pilot trial used a prospective, 2-group, randomized study design to evaluate a F&V intervention (N=46), where participants received a prescribed amount of fresh, base-producing F&V compared to a wait-list control (WL) condition (N=45). All participants were African American adults (≥18 years), had self-reported hypertension, and had CKD (Stage 1-3) on screening spot-urine microalbumin test. Participants were measured at baseline and 6 weeks post-intervention. Clinical data (i.e., systolic and diastolic blood pressure, lipid panel, hemoglobin A1C, BMI [body mass index], and albumin to creatinine ratio) were collected. Targeted metabolomic quantitative analysis was performed followed by LC-MS/MS and FIA-MS/MS. Linear mixed models evaluated analyte expression and clinical data. RESULTS/ANTICIPATED RESULTS: AA participants (N=91) were aged 58 ± 10.2 years, 66% female, and 54% had incomes ≤$50,000. T-tests compared change scores (baseline to 6-weeks) between groups. The F&V group demonstrated a significant reduction in BMI of -4.7 ± 10.5 kg/m² compared to a 1.9 ± 8.3 kg/m² increase in the WL group, p<.01. Further, the F&V group demonstrated a reduction in total cholesterol of -15.4 ± 58.8 mg/dL compared to a 17.7 ± 68.8 mg/dL increase in the WL group, p<.05. Non-significant reductions in hemoglobin A1c were found in the F&V versus the WL group. Metabolomic analysis indicated significant variation with an increase of suggestive key biomarkers for worse CKD in the WL versus F&V groups at 6-weeks. DISCUSSION/SIGNIFICANCE: Consumption of only 2 cups of F&V via a community-based intervention reduced CVD risk factors in AA adults with CKD and HTN and resulted in molecular/biochemical changes which may improve long-term kidney health. Further investigation may lead to development of cost-effective dietary intervention models to improve CKD outcomes in AA persons.

OBJECTIVES/GOALS: The major obstacle to an effective cure or remission for HIV infection is the integration of HIV into the genome of long-lived resting cells which constitute the so-called viral reservoir. With this study we want to elucidate the changes of the gut-associated HIV reservoir at different stages of viral suppression METHODS/STUDY POPULATION: Recent studies have shown that after long-term (>7 years) clinical suppression of peripheral HIV RNA, the circulating viral reservoir does not seem to decline further and, in fact may expand. The gastrointestinal associated lymphoid tissue (GALT) harbors by far the largest fraction of the latently infected cells, however not much is known about its changes over time.We thus quantified the HIV viral reservoir in the GALT by identifying HIV viral transcripts via 10X single-cell RNA sequencing at two GALT-sites in five PWH and compared the amount of HIV RNA found in the group of PWH with early (< 7years) vs late (> 7years) peripheral virological suppression (plasma HIV RNA <20copies/mL). RESULTS/ANTICIPATED RESULTS: Study participants had been diagnosed with HIV infection for a median (IQR) of 31 (32-34) years and had consistently undetectable peripheral blood HIV RNA for the previous 8 (4-15) years. In PWH with consistent viral suppression < 7yrs, 4 (2-6) HIV transcripts were identified in the ileum and 25 (13 – 38) in the colon. In PWH with consistent viral suppression > 7yrs, 0 (0-4) HIV transcripts were identified in the ileum and 7 (14-11) in the colon. Based on these preliminary results we plan to expand our cohort and confirm these results using Proviral DNA quantification. We anticipate that the viral decay in the GALT will follow a slower dynamic than what has been reported for the peripheral blood achieving a steady state after more than 7 years of peripheral viral suppression. DISCUSSION/SIGNIFICANCE: Despite the remarkable progress the survival and quality of life of PWH, after forty years from its first discovery, HIV infection remains uncurable. Considering its critical role, efforts are needed to better understand the dynamics of the GALT-associated HIV reservoir.

OBJECTIVES/GOALS: Maternal mental health, such as post-traumatic stress disorder (PTSD), is closely linked to child mental health. PTSD in mothers is associated with their children’s emotional responses. We examined associations between maternal PTSD and child brain function during emotion regulation. METHODS/STUDY POPULATION: Eight children ages 10-12 years, whose mothers had trauma histories, performed the Emotional N-Back task during functional MRI scanning. Mothers and children each reported on their trauma exposure and PTSD symptom severity. BOLD response to fearful faces during the Emotional N-Back was extracted from two specific brain regions of interest, amygdala and anterior cingulate cortex. These regions are involved in emotional response and attentional control, which are processes intrinsic to emotion regulation. An independent samples t-test was conducted on children’s BOLD response to fearful faces, with maternal PTSD symptom severity (high, low) as the independent variable. A parallel analysis was conducted with child PTSD symptom severity (high, low) as the independent variable. RESULTS/ANTICIPATED RESULTS: We found a main effect of maternal PTSD within brain regions of relevance to implicit emotion regulation. Compared to children whose mothers reported low PTSD symptom severity (n=4), children whose mothers reported high PTSD symptom severity (n=4) showed greater responsiveness to fearful faces in anterior cingulate cortex (t=2.04, p=.09,d=1.44) and amygdala (t=2.44, p=.05, d=1.72) at trending significance. A parallel analysis with child PTSD symptom severity showed no differences in brain function by this factor (ps=.55-.61). DISCUSSION/SIGNIFICANCE: Our pilot study is the first, to our knowledge, to examine associations between maternal PTSD and brain function during emotion regulation in their children. This study lays a foundation for future work; our goal is to explore dysfunction in emotion regulation neurocircuitry as one mechanism linking maternal PTSD to their children’s mental health.

OBJECTIVES/GOALS: The goal of this project is to characterize the efficacy of FOXA2 as a potential biomarker for patients with metastatic castrate-resistant prostate adenocarcinoma (CRPC) before transitioning to neuroendocrine prostate cancer (NEPC). NEPC currently has no therapeutic options and poor mechanistic understand of its origins. METHODS/STUDY POPULATION: In our study, we have utilized a multi-omics approach to characterize the potential efficacy of FOXA2 as a prognostic biomarker in numerous patient-derived castrate-resistant prostate cancer (CRPC) models. We have performed ATAC-, ChIP-, RNA-seq and proteomics to fully characterize where FOXA2 is binding genome-wide, how FOXA2 alters chromatin accessibility dynamics, identify regulatory gene targets of FOXA2, and identify FOXA2 protein-protein interactors. We have supported these findings using publicly available data from independent CRPC and NEPC patient cohorts and prostate cancer cell models. RESULTS/ANTICIPATED RESULTS: Our findings show that FOXA2 overexpression suppressed androgen signaling and promoted progression to a NEPC phenotype under short- and long-term androgen deprivation conditions, respectively. Further, FOXA2 redirected the chromatin accessibility landscape to be consistent with an NEPC gene expression program, including increased chromatin accessibility for key NEPC transcription factors. FOXA2 ChIP-seq showed FOXA2 to be bound at known NEPC driver genes and epigenetic modifiers across multiple stages of prostate cancer progression. Lastly, we discovered that FOXA2 physically interacts with key NEPC TFs and epigenetic regulators, suggesting that these FOXA2 physical interactions are required for NEPC progression. DISCUSSION/SIGNIFICANCE: This project will determine the efficacy of FOXA2 as a biomarker in advanced prostatecancer samples, which will translate as a potentially useful tool for clinicians to use for treatment of advanced prostate cancer patients.

OBJECTIVES/GOALS: To assess labels of drugs approved for Type 2 Diabetes (T2D) for the inclusion of geriatric sub-population data (ages 65-74, 75-84, ≥85) since January 1, 2013, in accordance with international guidance and US regulations in recognition of an aging populations and global demographics. METHODS/STUDY POPULATION: Utilizing FDA Guidance for Industry: Labeling for Human Prescription and Biological Products - Implementing the Physician’s Labeling Rule (PLR) Content and Format Requirements and the International Council for Harmonization of Technical Requirements (ICH) E7 guidance “Studies in Support of Special Populations: Geriatrics” as reference for assessing labels. The Center for Drug Evaluation and Research (CDER) new drugs/biologic approvals database was filtered for drugs approved between Jan. 1, 2013 and Dec. 31, 2022 with approved T2D indications. Examined original drug labels and supplements from Drugs@FDA for geriatric use efficacy and safety wording in Section 8.5 (Use in Specific Populations, Geriatric Use), for labels. Subpopulation data in labeling for ages 65-74, 75-84, and ≥85 was analyzed. RESULTS/ANTICIPATED RESULTS: Seven T2D drugs (Trulicity, Tresiba, Adlyxin, Ozempic, Steglatro, Kerendia, Mounjaro) approved within the specified time period were analyzed. In the current examination, all labels contain information regarding efficacy differences between ages 65+ and 75+, however, none contain information on efficacy for ≥85 populations. Four of the seven drugs have been updated with increased data from further efficacy trials for older adults conducted after initial approval. The remaining three drugs have only been reworded, or not changed at all, with no further efficacy trials conducted. DISCUSSION/SIGNIFICANCE: This research shows the gap in representation of older adults in clinical trial data and T2D drugs’ labeling. Despite having a higher usage of T2D drugs compared to the general population, older adults and especially the oldest-old (≥85) are underrepresented. Additional demographic requirements ensuring diversity in clinical trials is needed.

OBJECTIVES/GOALS: Electronic cigarettes have become increasingly popular, with various combustion products generated in the process. Dihydroxyacetone (DHA), a carbohydrate made during the heating process. Exposures may reach high micromolar to low millimolar doses of DHA per day and no studies have been done to understand the effects of DHA in the heart. METHODS/STUDY POPULATION: Here, we examine if DHA contributes to these using rat cardiomyocytes, H9c2 cells, and rat cardiac tissues to DHA evaluating metabolic and mitochondrial effects. Using the cells, we will investigate metabolic and mitochondrial pathways using Seahorse, protein expression changes in nutrient sensing pathways, and understand dose-dependent effects of DHA in the heart. Metabolite pools will also be evaluated to understand the changes promoted by DHA. Oxidative stress as previously observed in other cell models will also be measured. Key findings in the cardiac cells will be investigated in the cardiac tissues exposed to DHA. RESULTS/ANTICIPATED RESULTS: We have previously shown DHA induces oxidative stress, metabolic changes, and mitochondrial dysfunction in various cell line models. Interestingly, these effects are highly cell-type dependent. E-cigarettes are known to have toxic cardiac effects, including arterial stiffness, endothelial dysfunction, vascular injury, and oxidative stress. Changes in glycolytic, fatty acid synthesis, and the citric acid cycle enzymes and metabolites were found in the H9c2 cells. We also observed increased mitochondrial ROS and fuel changes due to DHA exposure. In DHA exposed cardiac tissues, we observed oxidative stress and mitochondrial fission and fusion dynamics altered. DISCUSSION/SIGNIFICANCE: These data suggest further study at physiologically relevant doses is warranted to understand how DHA inhaled impacts the long-term health of vapers. As well as the regulation of DHA in e-cigarettes as it has been deemed as safe for topical applications and warned against inhalation.

OBJECTIVES/GOALS: Socioeconomic status (SES) affects risk of disease and access to therapies. The expanded access (EA) pathway allows for the clinical use of investigational products for patients who have serious illness but no Food and Drug Administration (FDA)-approved therapeutic options. The SES of patients who receive EA is unknown. METHODS/STUDY POPULATION: We reviewed the patients who were approved for treatment through a single-patient EA pathway between 2018 and 2023. Using Michigan Medicine (MM) DataDirect software linked to the MM electronic medical record system, we linked the EA pathway patients to neighborhood data from the National Neighborhood Data Archive (NaNDA) to compare neighborhood related markers of affluence among EA patients and others treated at MM. We used descriptive statistics to compare variables between EA pathway patients and residents of the state of Michigan or the local county surrounding MM (Washtenaw County), using US Census tract data to provide context for these findings. RESULTS/ANTICIPATED RESULTS: MM patients who received EA treatments were more likely to come from neighborhoods that showed markers of high SES compared to residents of the state of Michigan but not Washtenaw County. This includes the proportion of persons living in poverty (12.5% EA / 13.4% Michigan / 12.4% Washtenaw) and education in the form of a bachelor’s degree or higher (32.2% / 30.6% / 57.2%). This varied by the disease being treated. Oncology patients were more likely to be from areas with less poverty and more education (12.4% / 76.8%) than the EA average. EA patients being treated for infectious diseases were from areas with more poverty and less education (13.5% / 26.7%). DISCUSSION/SIGNIFICANCE: Patients treated at Michigan Medicine using treatments obtained through the EA pathway came from areas that were, on average, more affluent than residents of the state of Michigan as a whole. This finding warrants more research to ensure equitable access to these therapies for patients in disadvantaged neighborhoods.

OBJECTIVES/GOALS: This study seeks to comprehensively evaluate the extent to which participants in clinical trials (CT) for Atopic Dermatitis (AD) accurately mirror the demographics and characteristics of the broader AD-affected populations. We will achieve this objective by analyzing data from AD CTs spanning the years 2011 to 2022. METHODS/STUDY POPULATION: We examined completed trials for 10 FDA approved treatments for AD, utilizing data sourced fromclinicaltrials.gov [http://clinicaltrials.gov]. In light of the increased number of AD clinical trials over the past decade, we tailored our search parameters to encampass all trials related to approved treatments from 2011-2022. To assess the characteristics of the participant population in these trials, information including inclusion and exclusion criteria, age, location, sex, and disease severity were collected for each trial. Furthermore, race and ethnicity data were also extracted and analyzed. Additionally, comparisons were drawn between trials completed before and after April 2017, when the FDA began requiring that researchers publish race and ethnicity data toclinicaltrials.gov [http://clinicaltrials.gov]. RESULTS/ANTICIPATED RESULTS: Across 67 CTs examined, 45% of trials were restricted to adult patients, 28% were restricted to pediatric patients, and 27% included both. 77% of CTs occurred in urban settings and 23% occurred in rural settings according to the The Economic Research Service definition. 36% of CTs included mild-to-moderate AD patients, and 64% of CTs included moderate-to-severe AD patients. Race distribution of CTs revealed 67% White, 14% Black/African American, 16% Asian, and 3% others. 13% of participants identified as Hispanic or Latino. With further analysis, we will determine whether there is a difference in ethnic distribution between trials completed before and after April 2017, when the FDA started requiring race/ethnicity data to be submitted. DISCUSSION/SIGNIFICANCE: The findings highlight a significant concern in AD CTs: the insufficient representation of Black and Asian populations. The findings emphasize the need for a more inclusive selection process that accurately reflects the diversity of patients. Failing to do so could undermine the assessment of treatment effectiveness in such populations.

OBJECTIVES/GOALS: To compare the herbal medicine (HM) programs of the U.S. to those of different countries–including the European Union, South Korea, China, and India–and to examine each regulatory body’s process for obtaining market approval for HM drugs. METHODS/STUDY POPULATION: The European Union, South Korea, China, and India’s respective HM regulatory programs were examined and compared to the U.S. FDA’s HM process. These specific regulatory bodies were chosen based on the country’s long history with HM and/or the robustness of their existing HM review processes. International HM programs were researched using official government websites and journals published by independent, external research institutions that were accessed via USC’s library services. Data regarding the efficacy of HM policies such as HM IND approval rates, number of marketed HM drugs, and establishment of unique HM sectors will be collected. RESULTS/ANTICIPATED RESULTS: Investigational New Drug (INDs) applications regarding HM from each country will be categorized and displayed according to their approval status in order to provide insight on a HM program’s efficiency. Results also included a table displaying common challenges for approval for HM drugs across federal regulatory bodies. If applicable, effective solutions implemented to address some of these obstacles that proved to be effective will also be displayed in the form of a table. DISCUSSION/SIGNIFICANCE: Tables displaying the collective flaws of international HM programs and the resulting regulatory solutions can provide clearer guidance for companies seeking to submit HM INDs and for the U.S. FDA seeking to develop improved HM regulations.

OBJECTIVES/GOALS: Physicians can request the clinical use of investigational products for their patients through an FDA pathway called Expanded Access (EA). Most evaluations of EA focus on the FDA submission only. We sought to evaluate these requests through the full academic medical center process. METHODS/STUDY POPULATION: Through the Transforming Expanded Access to Maximize Support and Study grant, we reviewed regulatory records for single-patient EA requests at four institutions (Duke University, University of Rochester, University of Michigan, and University of Texas Southwestern) which occurred between June 1, 2021 and February 28, 2023. Key data was collected, including the investigational product requested, submission and approval dates, urgency of request, and indication for treatment. Descriptive statistics were performed with Microsoft Excel. RESULTS/ANTICIPATED RESULTS: A total of 405 EA requests were identified, of which 319 (78.8%) were for drugs, 59 (14.6%) for biologics, and 27 (6.7%) for medical devices. The majority were characterized as non-emergency (60.7%), but the proportion of emergency to non-emergency cases varied considerably when stratified by year, with a peak in emergency cases in 2020. The most common products included therapies for COVID-19 and Mpox. Median time to obtain all approvals for treatment was 7 days for emergency cases and 28 days for non-emergency. The FDA review took the least time, with a median of 1 day in non-emergency cases. Full board approval from an institutional review board in non-emergency cases was 7 days. DISCUSSION/SIGNIFICANCE: These results generally align with previous reports on EA submissions received by the FDA. The timelines for the EA process represent an important benchmark both for treatment planning and institutional improvement.

OBJECTIVES/GOALS: The primary purpose of the QA/QC Project Manager (PM), appointed under the NCATS UL1 administrative supplement award, is to facilitate quality and timely NCATS prior approval submissions preventing study start delays. Other goals include supporting these projects’ IRB applications and monitoring to ensure data quality and compliance. METHODS/STUDY POPULATION: At the Indiana CTSI, the QA/QC PM is assigned to the Regulatory Knowledge and Support program (RKS) and functions as a unique regulatory service provider. Through monitoring, auditing, and personalized consultations, the IN CTSI QA/QC PM provides study teams with regulatory, GCP, and other compliant study conduct insights while managing NCATS prior approval and RPPR submission quality and timeliness. In contrast to many CTSAs, this role is uniquely situated within RKS and provides QA/QC support through a regulatory lens. The Indiana CTSI QA/QC PM serves on the CTSA QA/QC Lead Team collaborating with NCATS and other CTSA QA/QC personnel. The Lead Team engages with NCATS to host monthly/quarterly meetings and participate in a discussion forum of NCATS and other CTSA QA/QC personnel. RESULTS/ANTICIPATED RESULTS: Not all CTSAs employ the QA/QC PM as regulatory support and the role and skill sets at each CTSA vary, yet the collaborative nature of these individuals across the CTSAs facilitates sharing of resources and knowledge. While prior approval and RPPR submissions vary widely, the QA/QC PMs can rely on their counterparts for guidance complying with the same regulations and policies within unique research settings and institutional nuances. The IN CTSI QA/QC PM, in collaboration with the QA/QC Lead Team, provided quality assurance revisions to the NCATS prior approval instructions which were adopted and published by NCATS January 2022 for implementation at all CTSAs. Ongoing, quality control efforts are accomplished through education, monitoring, and regulatory consultations. DISCUSSION/SIGNIFICANCE: As the research environment evolves, the QA/QC PM responsibilities shift in response to needs within RKS and NCATS. The versatility of the position enables QA/QC to occur at all stages of a study. QA/QC strategies aim to facilitate communication, quality NCATS prior approval and RPPR submissions, and compliance with proposed study conduct.

OBJECTIVES/GOALS: To identify challenges faced by academic researchers in accessing online regulatory information and/or tools to advance their research work to develop a free, publicly accessible, interactive web portal that provides regulatory support. METHODS/STUDY POPULATION: The Regulatory Knowledge and Support core of the Southern California Clinical and Translational Science Institute interviewed five local research professionals. These interviews guided the development of a Qualtrics survey, consisting of multiple responses and open-ended questions, submitted to our local institutional review board (IRB). After receiving IRB approval, the survey was disseminated via email, newsletters, flyers, and presentations targeting researchers at academic institutions and members of clinical and translational science hubs. Survey data will be used to identify the challenges academic researchers face in finding regulatory resources and to compile the types of regulatory information or tools they would find helpful for their research. RESULTS/ANTICIPATED RESULTS: According to the interviews, researchers with extensive involvement in clinical trials found regulatory resources easily accessible compared to those with less experience. Additionally, they all stated having a colleague or regulatory specialist whom they can consult about regulatory requirements. Insights from these initial interviews confirmed the need to obtain a comprehensive view across research professionals. Anticipated results will show the challenges in accessibility, source, and type of regulatory resources researchers typically encounter. It is also anticipated that researchers will share what kinds of resources they would find most useful for their work. Ultimately, the information and tools identified as essential by survey takers will be collected and incorporated into the web portal. DISCUSSION/SIGNIFICANCE: Academic researchers find navigating through regulatory hurdles persistently challenging when translating their work from bench to clinic, especially since academia is typically resource-constrained. Findings from this study will allow the creation of a web portal for researchers that is broadly accessible and meets their regulatory needs.

OBJECTIVES/GOALS: Examine the use of Patient-Reported Outcomes (PRO) in Huntington’s Disease (HD) clinical trials (CT) and compare across time and sponsor types. METHODS/STUDY POPULATION: Conduct literature review on 1. background of HD, 2. what symptoms and outcome measures are most important to patients, including the Patient-Focused Drug Development (PFDD) meeting for HD–led by the U.S. Food and Drug Administration (FDA), 3. what outcome measure tools currently exist and what they measure. Utilizing Clinicaltrials.gov, trials for HD were examined to assess the number of trials conducted, what COAs were used, and funding types. Trials were filtered by study type (keep Interventional) and status (filter out suspended, terminated, unknown, and withdrawn). The frequency of COAs will then be mapped based on the symptoms from the PFDD meeting. RESULTS/ANTICIPATED RESULTS: From the PFDD meeting for HD, symptoms that were important to patients include cognitive impairment, depression and anxiety, and motor symptoms. From the 139 interventional studies that were active, complete, recruiting, or not recruiting, 79 studies were conducted by Industry, 3 by NIH, 93 by Other (Academia/Community Organizations), and 1 by a U.S. Federal Agency (other than NIH). One of the most commonly used COA is the Unified Huntington’s Disease Rating Scale (UHDRS), which includes a motor, cognitive, and behavior assessment, and an assessment on functional capacity and independence. Of the 27 out of 139 trials analyzed to date, there were a total of 37 COAs. DISCUSSION/SIGNIFICANCE: The widespread use of UHDRS can be attributed to its standardization in 1999. It captures the symptoms of HD that are most important to patients. Because UHDRS is not sensitive to any one symptom, other COAs have been developed which focus on unique aspects of HD and allow for its earlier detection.

OBJECTIVES/GOALS: The FDA allows physicians to request clinical use of investigational drugs, biologics, and devices for patients with no satisfactory treatment options through a pathway called Expanded Access (EA). TEAMSS (Transforming Expanded Access to Maximize Support and Study) sought to examine single-patient cases to better characterize these patients. METHODS/STUDY POPULATION: We prospectively collected data on requests for single-patient EA at any one of the four collaborating TEAMSS institutions (Duke University, University of Rochester, University of Michigan, and University of Texas Southwestern) between September 1, 2021 and February 28, 2023. Regulatory and health records were reviewed for past cases that occurred between June 1, 2018 and August 31, 2021. Descriptive statistics were performed on data from the submission process, the patient demographics, the indication for treatment, and patient health status over time. RESULTS/ANTICIPATED RESULTS: The patient population was representative with respect to the largest racial groups (69.3% White / 13.0% Black or African American) and legal sex (51.3% male / 48.7% female). All ages were represented, with overrepresentation of those 60-70 years old (16.8%) and under 10 (14.8%). Patients were most often treated for infectious diseases (44.2%) or oncologic conditions (39.0%). Those who received more than one dose stayed on treatment for 76 days (median) and up to 1427 days (maximum). At the end of study, 53.9% had completed treatment as planned, moved to commercial product, or continued treatment. Death, disease progression, or failure to respond occurred for 31.9% of patients. DISCUSSION/SIGNIFICANCE: The population that receives Expanded access treatments is heterogeneous in both demographics and medical conditions. Some successful treatments are continued for years. Many patients complete their treatment, and a minority experience death or disease progression during treatment.

OBJECTIVES/GOALS: Mayo Clinic (MC) launched the Rapid Activation Trial (RAT) pilot program in 2022 to expedite the activation of high priority and high impact clinical trials. The objective was to develop a process for rapid activation through robust screening, prioritization, and project management (PM) support. METHODS/STUDY POPULATION: The project team developed a robust screening and approval process for the RAT program using a combination of an objective scoring tool (based on strategic priorities) and a diverse selection committee to screen and approve eligible trials. Sponsors had to commit to RAT program timelines. Upon approval, trials were prioritized at the highest level within each business unit involved in the activation process. The number of trials approved annually were limited to 8 to manage volume and facilitate seamless prioritization with an activation timeline goal of 6 weeks. Project management support for RAT program focused on financial, regulatory, logistical, and operational elements to open trials expeditiously. RESULTS/ANTICIPATED RESULTS: In 2022, thirteen (13) applications were received and eight (8) were approved by the RAT selection committee. The approved trials activated with a median open to enrollment time of 6.4 weeks from engaging with business units. They also aligned closely with organization’s strategic priorities, including but not limited to Investigator Initiated Trials, Multi-Site protocols, IND/IDE protocols, Rare Diseases, First in Human and Commercialization potential trials. PI and study team feedback was positive. In 2023, the RAT program was renewed due to the pilot’s significant success in 2022. The goal is to open 10 trials and 5 have been activated by the end of Q3, 2023 with a median timeline of 6 weeks. DISCUSSION/SIGNIFICANCE: Rapid activation of high priority and high impact clinical trials enables an organization to strategically prioritize and open complex clinical trials. This allows the delivery of innovative, timely cures to patients in an expeditious timeline.

OBJECTIVES/GOALS: To establish and develop a high-level, dynamic, and self-sustainable Translational Science – research center in Colombia that promotes and articulates collaborative participation among different disciplines at Universidad de La Sabana to generate impactful solutions in health to transfer the knowledge to the local community. METHODS/STUDY POPULATION: With the support of core units of the University, internal funding was given for the establishment of the Research Center. An internal call was performed for recruiting researchers for multiple disciplines interested in joining the UCTS. After the researchers were selected, training of the research community in translational science and funding acquisition was performed towards the objective of interdisciplinary projects with impact in the local community. Project management strategies have been used for the follow-up of the advancements of the implementation of the UCTS. Operational structure and business plan for future self-sustainability are being designed. UCTS is proposed as an articulating party among different actors in clinics, research, and industry, for science and funding management. RESULTS/ANTICIPATED RESULTS: As an starting point, 8 research groups of different disciplines of the University have been integrated with the UCTS, increasing the research capacity in translational science. Internal administrative processes have been articulated within the institution and unified processes for international grants applications have been established in order to optimize the funding acquisition and management. Training programs for the research community, and community engagement activities have been offered as well. Networking relationships have been strengthened among the researchers enhancing international collaborations. Novel research projects are being designed towards real solutions in health for the local community, promoting the transference of knowledge from the benchside to the community. DISCUSSION/SIGNIFICANCE: The implementation of the UCTS led to the integration of disciplines within the University, towards new research projects with common interests for the local community. It has been an enriched experience using the project management approach, fulfilling a huge milestone for the University, aligned with the internal strategic priorities

OBJECTIVES/GOALS: High turnover rates of clinical trials staff pose obstacles to the quality and efficiency of conducting clinical trials. We have explored alternative staffing models to address these translational barriers and to improve the financial viability and return on investment of a centralized clinical trials office. METHODS/STUDY POPULATION: Implementation of an alternative clinical trials staffing model that leveraged burnout rates in clinical service areas by hiring APPs, RNs, EMTs, OTs and PTs in tandem with traditional CRAs/CRCs. Financial modelling of employing higher salaried clinical professionals was analyzed with regards to greater staff retention, trials efficiency, and operational cost savings. RESULTS/ANTICIPATED RESULTS: Since 2014, 30 of 51 (59%) staff left the clinical trials office with 49% of these leaving prior to 2 years employment. Using average local CRCII compensation values, the costs associated with these transient staff amounted to $2.51 million (i.e., recruitment, replacement, and training). Models of staffing that replace 2 CRAs, 2 CRCIs and 2 CRCIIs with an RN, APP, CRCI and 3 CRAs increases compensation by 24.1%. This increase, however, is offset by greater workload capacity, retention, and more efficient trials operations. In addition, revenue generating PI clinical activity is sustained by employing credentialed APPs for study visits. DISCUSSION/SIGNIFICANCE: Long-term financial savings and greater clinical trial operational efficiency may be accomplished by seeking clinical professionals looking for alternative opportunities with greater work-life balance while leveraging their advanced clinical skills and licensing.

OBJECTIVES/GOALS: In a 2022 NASEM Report, “… successful inclusion of underrepresented populations in research is investing in diverse research teams to enhance congruence and to optimize recruitment and retention success.” Thus, academic research institutions must provide safe, respectful and inclusive work environments to support diverse research teams. METHODS/STUDY POPULATION: Resources, policies and protocols related to disruptive research participants have not been well articulated at our institution. Given this dearth of information, we launched a new initiative across our CTSA, IRB, Office of General Counsel and Department of Population Health. The multipronged approach includes: 1) Conduct a scoping review of published and gray literature to identify best practices, trainings and resources to mitigate discrimination, harassment of research team members; 2) Co-develop new institutional policies and procedures to ensure safety and respect for both research staff and participants; 3) Develop an online training on research team field and workplace safety; and 4) Widely disseminate policies and resources to address the overall gap in academic research. RESULTS/ANTICIPATED RESULTS: Our ongoing scoping review has shown that here is an overall lack of information on bias, discrimination and harassment perpetrated by research participants towards research teams. Based on our activities, new Human Research Protection policies were launched. These include defining what disruptive participant behavior in research is, the introduction of a Statement on the Conduct of Participants in Research Studies, and steps study teams may implement to manage disruptive behavior initiated by a research participate. Next steps include the development of training resources for study teams on the new policies and to introduce de-escalation and situational awareness strategies and trainings. DISCUSSION/SIGNIFICANCE: As research teams become increasingly diverse, there is a need to better support them and ensure that the research field and work settings are safe, inclusive environments with articulated policies that mitigate/prevent discrimination, bias and harassment perpetrated by study participants.