627. CURE ID as a Tool for Curating and Analyzing Drugs Used in COVID-19 Clinical Trials

Abstract Background CURE ID is an internet-based data repository (https://cure.ncats.io/explore) developed collaboratively by FDA and NCATS/NIH. It is designed to capture real-world clinical outcome data to advance drug repurposing and to inform future clinical trials for infectious diseases with high unmet medical need. It also serves as a repository of clinical trials automatically pulled from https://www.clinicaltrials.gov into the CURE ID platform, where they were then manually curated, with the intention of keeping the infectious diseases community updated on the various clinical trials underway. The current study is a descriptive analysis of various therapeutics in clinical trials against COVID-19 on the CURE ID platform. Methods Using clinicaltrials.gov we selected those trials addressing therapeutics for COVID-19 and reviewed the drugs used, the current status of the trials, and the phases of development. Results As of May 2021, we identified 2,154 clinical trials and 933 drugs from clinicaltrials.gov that met the inclusion criteria. Hydroxychloroquine (n=251) was the most commonly investigated agent, followed by convalescent plasma (n=147), azithromycin (n=98), ivermectin (n=68), mesenchymal Stem Cells (n=63), tocilizumab (n=58), remdesivir (n=53) and favipiravir (n=51). At the time of our analysis, the majority (45%) of the clinical trials were in the recruiting phase, 12% were in the active phase, and 13% of the studies were completed. The majority (31%) of trials were in phase two, followed by phase three (21%) and phase one (10%). The vast majority of the agents were repurposed (92%), while only 8% of the agents were new molecular entities. Remdesivir was the only drug approved for marketing for treatment of certain patients with COVID-19 at the time of our analysis. Conclusion Several repurposed and novel drugs are being investigated to treat COVID-19 in clinical trials. CURE ID provides a broad view of the various drugs being researched and serves to keep the scientific community informed. Such a platform may help prevent duplication of efforts and help the scientific community with more coordinated research efforts and larger platform trials that can robustly answer scientific questions during a pandemic. Disclosures All Authors: No reported disclosures


Session: P-28. Clinical Trials
Background. DRIVE-FORWARD is a phase 3 trial with a completed double-blind period comparing doravirine (DOR) 100 mg with ritonavir-boosted darunavir (DRV/r) 800/100 mg, both administered with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs; tenofovir and emtricitabine, or abacavir and lamivudine), and an ongoing open-label extension. At Week (W) 48, DOR demonstrated non-inferior efficacy to DRV/r, with a superior lipid profile. Those results were sustained at W96. Here we present efficacy and safety results through W192.
Methods. Participants who completed the 96-week double-blind phase and met inclusion criteria were eligible to receive open-label DOR plus two NRTIs in a 96-week extension. Efficacy and safety at W192 were assessed in two groups: participants initially randomized to DOR and maintained on DOR (n=259) and those who switched from DRV/r to DOR at W96 (n=233).
Results. HIV-1 RNA < 50 copies/mL were maintained through W192 in 81.1% of participants who continued DOR and 80.7% of those who switched from DRV/r to DOR. The mean increase in CD4 T-cell counts from W96 to W192 was similar for participants maintained on DOR (47 cells/mm 3 ) and those switched from DRV/r (53 cells/ mm 3 ). Protocol-defined virologic failure occurred in 3.1% and 5.6% of participants maintained on DOR and switched from DRV/r, respectively, and development of genotypic resistance was low in both groups (Table 1). Discontinuation due to adverse events was also low (Table 1). Fasting LDL-cholesterol, non-HDL-cholesterol, and triglycerides showed minimal increase in participants maintained on DOR and were reduced in those switched from DRV/r to DOR (Table 1). Participants maintained on DOR had minimal weight gain after W96 (median 1 kg), and a small increase overall (median 1.9 kg, Day 1 through W192); participants who switched to DOR had a small increase after W96 (median 1.5 kg), similar to the median weight gain in the base study (DOR 1.8 kg; DRV/r 0.7 kg).
Conclusion. Among participants who continued DOR in the DRIVE-FORWARD open-label extension, virologic suppression and favorable safety were maintained for an additional 96 weeks. Participants who switched from DRV/r to DOR maintained virologic suppression and demonstrated favorable safety for 96 weeks. Background. CURE ID is an internet-based data repository (https://cure.ncats. io/explore) developed collaboratively by FDA and NCATS/NIH. It is designed to capture real-world clinical outcome data to advance drug repurposing and to inform future clinical trials for infectious diseases with high unmet medical need. It also serves as a repository of clinical trials automatically pulled from https://www.clinicaltrials.gov into the CURE ID platform, where they were then manually curated, with the intention of keeping the infectious diseases community updated on the various clinical trials underway. The current study is a descriptive analysis of various therapeutics in clinical trials against COVID-19 on the CURE ID platform.
Methods. Using clinicaltrials.gov we selected those trials addressing therapeutics for COVID-19 and reviewed the drugs used, the current status of the trials, and the phases of development.
Results. As of May 2021, we identified 2,154 clinical trials and 933 drugs from clinicaltrials.gov that met the inclusion criteria. Hydroxychloroquine (n=251) was the most commonly investigated agent, followed by convalescent plasma (n=147), azithromycin (n=98), ivermectin (n=68), mesenchymal Stem Cells (n=63), tocilizumab (n=58), remdesivir (n=53) and favipiravir (n=51). At the time of our analysis, the majority (45%) of the clinical trials were in the recruiting phase, 12% were in the active phase, and 13% of the studies were completed. The majority (31%) of trials were in phase two, followed by phase three (21%) and phase one (10%). The vast majority of the agents were repurposed (92%), while only 8% of the agents were new molecular entities. Remdesivir was the only drug approved for marketing for treatment of certain patients with COVID-19 at the time of our analysis.
Conclusion. Several repurposed and novel drugs are being investigated to treat COVID-19 in clinical trials. CURE ID provides a broad view of the various drugs being researched and serves to keep the scientific community informed. Such a platform may help prevent duplication of efforts and help the scientific community with more coordinated research efforts and larger platform trials that can robustly answer scientific questions during a pandemic.

Session: P-28. Clinical Trials
Background. Increase of carbapenem-resistant Enterobacterales (CRE) is a serious problem in the clinical setting and drugs which can treat patients with CRE are still limited. Nacubactam (OP0595) is a novel diazabicyclooctane-type β-lactamase inhibitor and being developed as a standalone drug to be co-administered with cefepime or aztreonam.
Methods. A randomized, double-blind multiple dose study of nacubactam in co-administration with cefepime (Cohort 1) or aztreonam (Cohort 2) in Japanese healthy subjects was performed to assess pharmacokinetics, safety, and tolerability of co-administrations of nacubactam and cefepime or aztreonam. In each cohort, 6 subjects received 2 g of nacubactam and 2 g of concomitant drug (cefepime or aztreonam) and 2 subjects received placebo (saline) intravenously over 60 minutes, three times daily every 8 hours for 7 days. Plasma samples were collected and concentrations of each drug were analyzed by liquid chromatography-mass spectrometry (LC-MS/ MS). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and the evaluation of changes from baseline in safety laboratory test results, 12-lead electrocardiograms (ECGs), vital signs, and physical examinations.
Results. Profiles of C max , t max , AUC 0-8 , AUC 0-∞ and t 1/2 for nacubactam, cefepime and aztreonam are summarized in Table 1. Summary of C trough for nacubactam, cefepime and aztreonam are summarized in Table 2. Plasma concentrations of nacubactam, cefepime and aztreonam reached the steady-state by Day 4, and the mean accumulation ratios of C max and AUC 0-8 on Day 7 to those of Day 1 were in the range of 0.91 to 1.10. As for the safety, no serious adverse event was observed in this study. There was 1 TEAE (seborrhoeic dermatitis) leading to the discontinuation in 1 subject in nacubactam/cefepime group, but it was judged as "Not related to study drug".

Conclusion.
In conclusion, no remarkable change in pharmacokinetics was observed in each drug with multiple concomitant administration for 7 days and safety and tolerability of co-administrations of nacubactam and cefepime or aztreonam were confirmed. Based on these results, nacubactam is currently under further development.