Safety, Pharmacokinetics and Preliminary Efficacy of IL4-Rα Monoclonal Antibody AK120 in Both Healthy and Atopic Dermatitis Subjects: A Phase I, Randomized, Two-Part, Double-Blind, Placebo-Controlled, Dose-Escalation, First-In-Human Clinical Study.

INTRODUCTION: Interleukin-4 (IL-4) and interleukin-13 (IL-13) are two essential cytokines involved in the T helper 2 (Th2)-mediated inflammatory response to diseases, such as atopic dermatitis (AD). AK120 is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) directed against the IL-4 receptor alpha (IL-4Rα) subunit shared by the IL-4 and IL-13 receptor complexes. This mAb inhibits the signaling of the IL-4 and IL-13 cytokines. METHODS: The study consisted of two parts. Part 1 was a single ascending dose (SAD) study with five cohorts (receiving 15, 50, 150, 300 or 600 mg of AK120, respectively) of healthy subjects; part 2 was a multiple ascending dose (MAD) study with four cohorts (receiving AK120 at doses of 300 mg once every 2 weeks [Q2W], 300 mg once weekly [QW], 150 mg QW or 75 mg QW) of subjects with AD. A total of 81 subjects (40 in part 1, 41 in part 2) were enrolled in the study. RESULTS: The compound was safe and well tolerated in both a SAD up to 600 mg in healthy subjects and in a MAD from 75 to 600 mg in subjects with AD. The exposure of AK120 increased in an approximately dose-dependent manner upon subcutaneous dosing. The levels of the biomarkers serum thymus and activation-regulated chemokine ligand 17 (TARC/CCL17) and immunoglobulin E decreased from baseline after AK120 administration, indicating the inhibition of the IL-4/IL-13 signaling pathways. AK120 showed improved Eczema Area and Severity Index (EASI) scores, and the proportion of subjects with Investigator Global Assessment (IGA) score 0/1 increased after AK120 treatment. CONCLUSIONS: AK120 exhibited an acceptable safety profile in healthy and AD subjects, and showed preliminary efficacy. These findings support the continued investigation of AK120 for treating AD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identification number: NCT04256174.

Design of an internationally accredited radiation oncology resident training program incorporating novel educational models.

PURPOSE: Our primary aim was to design a new, internationally accredited, comprehensive radiation oncology (RO) training program for Singaporean residents that satisfied the needs of stake holders and incorporated published evidence. METHODS AND MATERIALS: The evidence-based method included Medline literature review and broad-based training needs assessment. RESULTS: Literature review revealed few studies describing or evaluating RO resident training programs. Our program was designed by incorporating available published research and stakeholder views determined by the training needs assessment. The program includes novel evidence-based educational methods, including individually negotiated learning contracts, a mentor program, logbooks, task-based learning, tutorials, and formative plus summative assessments. The content and structure is consistent with most United States, United Kingdom, and Royal Australian and New Zealand College of Radiologist (RANZCR) guidelines, with resident evaluation via RANZCR examinations. The RANZCR accredited the program in January 2002. CONCLUSION: We recommend institutions or countries introducing or revising RO resident training programs use an evidence-based approach, addressing the needs of stake holders (determined by a comprehensive training needs assessment) and incorporating published research. Novel educational methods may be considered in RO training. This new Singapore program is the first to achieve international accreditation by the RANZCR. It is clear that additional research in the design and evaluation of RO resident training programs is required.