Introduction and Objective: CNP-103 is an investigational nanoparticle encapsulating four recombinant islet antigens designed for the treatment of type 1 diabetes (T1D). The CNP platform harnesses immunoregulatory pathways to induce antigen-specific tolerance and has shown strong efficacy in various preclinical models of autoimmunity. In NOD mice, treatment with a surrogate CNP-103 (CNP-T1D) protected mice from diabetes and reversed dysglycemia. In clinical trials involving celiac disease and primary biliary cholangitis, the CNP platform was safe and efficacious at restraining disease-specific T cells. Here, safety results from an ongoing trial with CNP-103 in new-onset T1D patients are described. Methods: This randomized, double-blind, placebo-controlled Phase 1b/2a study will enroll 72 subjects, aged 12-35, with diagnosis of T1D 6 months from enrollment and a peak stimulated C-peptide 0.2 nmol/L. The escalation phase of this study will evaluate the safety of multiple ascending doses (100 to 600 mgs) of CNP-103 administered intravenously on days 1, 8 and 90 in adult and pediatric cohorts with primary assessments on Day 180 and Day 365. Each cohort will consist of up to 6 subjects randomized 2:1 (active to placebo) with pediatric cohorts following adults after a safety review prior to transition between dose levels. Exploratory endpoints include change in C-peptide (AUC) from baseline and T cell assays to characterize longitudinal changes in β-cell function and islet-specific T cells. Results: Adult Cohort 1 (100 mg) had a mean age of 26.9 years, gender 1:5 (female:male), and a mean disease duration of 85.9 days. No infusion interruptions occurred in the 6 subjects dosed on day 1 and 8. The most common AEs reported in 1 or more subjects were: sinus discomfort, pre-syncope, decreased PMN count and low vitamin D; none were considered IP-related. No SAEs were reported. Conclusion: Early data with CNP-103 shows good tolerability. The trial is ongoing. Disclosure S.K. Patel: None. J. Gaglia: Consultant; Current; Vertex Pharmaceuticals Incorporated, AstraZeneca, polTreg. Research Support; Current; Sanofi. Stock/Shareholder; Current; Vertex Pharmaceuticals Incorporated. T.M. Triolo: None. E. Hong: Employee; Current; Cour Pharmaceutical Development Company. M. Frey: Employee; Current; COUR Pharma. J.R. Podojil: None. D.P. McCarthy: Employee; Current; COUR Pharmaceuticals. K.S. Cerosaletti: Research Support; Current; Cour Pharmaceuticals, GentiBio, Inc, InduPro Therapeutics. Consultant; Ended; Mozart Therapeutics. Other - Research collaboration supported by Breakthrough T1D grant funding; Ended; Base5 (Benthic) Genomics. Research Support; Ended; IM Therapeutics. A. Elhofy: None. P.M. Peloso: Employee; Current; COUR Pharma.
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