Sanofi (Czechia)

BackgroundChronic inducible cold urticaria (ColdU) is characterized by itchy wheals (hives) with or without angioedema induced by cold exposure. It severely impacts patients’ health-related quality of life (HRQoL). Qualitative research describing the burden of ColdU from direct patients’ voice remains sparse. The study aims to explore the patients’ ColdU experience by identifying signs, symptoms, and associated impacts, and to develop the first conceptual model for ColdU from the patients’ perspective.MethodologyOne-to-one telephone concept elicitation (CE) interviews were conducted with patients with ColdU between 2022 and 2023. Participants were asked open-ended questions about their experience of the signs, symptoms and impacts and the most and least bothersome aspects of their disease.ResultsEight adults and 5 adolescent participants interviewed reported 22 ColdU-related symptoms/signs and 32 impacts. Six children/caregiver dyads and 1 caregiver of a 2-year-old child with ColdU reported 17 ColdU-related symptoms/signs and 19 impacts. Patient experience of symptoms and impacts was similar across all age groups, with hives and itch reported most frequently as the most bothersome symptoms. Similarly, for impacts, all participants reported impairment in activities of daily living (e.g., not taking part in hobbies, wearing warm clothes). Two conceptual models of patients’ experience of ColdU (one for adult/adolescent patients and one for pediatric patients) were developed.ConclusionsThis study is the first to report the ColdU experiences directly from patients. It identifies hives and itch as being the core symptoms and describes the debilitating nature of ColdU and its substantial impact on the HRQoL of all age ranges.

Abstract RATIONALE: Achieving meaningful improvements in asthma control remains an unmet need. Rilzabrutinib is an investigational oral Bruton's tyrosine kinase inhibitor. In a phase 2 proof-of-concept study, there was a reduction in loss of asthma control (LOAC) events with rilzabrutinib vs placebo at Week 12 in participants with poorly controlled moderate-to-severe asthma. Here, rescue medication use during the treatment period is reported. METHODS: This was a 12-week, double-blind, placebo-controlled, 2-staggered-cohort study in adults with moderate-to-severe asthma who were poorly controlled on inhaled corticosteroid (ICS)/long-acting β2 adrenergic agonist (LABA) therapy (NCT05104892). 196 eligible participants were randomized 1:1 first to rilzabrutinib 800mg (400mg twice daily; N=32) or placebo (N=32), and then to rilzabrutinib 1200mg (400mg three times daily; N=64) or placebo (N=68) added to medium-to-high-dose ICS/LABA, which was withdrawn Weeks 4-9. The primary endpoint was the proportion of participants with a LOAC event over 12 weeks. The use of ≥6 additional reliever puffs of a short-acting β2 adrenergic agonist (SABA) in a 24-hour period vs baseline on 2 consecutive days was one criterion for a LOAC event. Exploratory outcomes were the use of ≥2-5 additional reliever puffs of SABA for symptom relief vs baseline on 2 consecutive days over 12 weeks. RESULTS: At Week 12, the reduction in LOAC events observed with rilzabrutinib was mostly driven by a decrease in the proportion of participants requiring rescue medication defined as ≥6 additional reliever puffs, with 6.3% vs 12.5% for rilzabrutinib 800mg vs placebo (relative risk reduction [RRR]: 50%) and 0% vs 10.3% for rilzabrutinib 1200mg vs placebo (RRR: 100%), respectively. An overall reduction in participants requiring SABA with rilzabrutinib was observed across different thresholds over 12 weeks: 9.4% vs 21.9% for rilzabrutinib 800mg vs placebo (RRR: 57%) and 6.3% vs 23.5% for rilzabrutinib 1200mg vs placebo (RRR: 73%), respectively, required ≥3 additional reliever puffs; 6.3% vs 18.8% for rilzabrutinib 800mg vs placebo (RRR: 66%) and 4.7% vs 17.6% for rilzabrutinib 1200mg vs placebo (RRR: 73%), respectively, required ≥4 additional reliever puffs; and 6.3% vs 12.5% for rilzabrutinib 800mg vs placebo (RRR: 50%) and 1.6% vs 14.7% for rilzabrutinib 1200mg vs placebo (RRR: 89%), respectively, required ≥5 additional reliever puffs. CONCLUSIONS: Rilzabrutinib treatment in participants with poorly controlled moderate-to-severe asthma was associated with a reduction in LOAC events, which was mainly driven by a reduction in SABA use. Overall, the use of SABA was reduced with rilzabrutinib vs placebo in both cohorts over 12 weeks.

Abstract Dupilumab is the only FDA-approved systemic therapy for prurigo nodularis (PN), however, immunosuppressants (IS) and phototherapy have been used off-label for the treatment of this condition. Patients with prior IS/phototherapy treatment may represent a more severe and/or treatment-refractory population of patients with PN. Report post-hoc efficacy of dupilumab in patients with PN, with or without prior use of IS or phototherapy for PN. LIBERTY-PN PRIME and PRIME2 (NCT04183335 and NCT04202679) are randomized, 24-week, phase 3 studies in adults with PN that is inadequately controlled by topical prescription therapies or for whom those therapies are not advisable. Primary outcomes included a ≥4-point improvement in the weekly average of Worst Itch Numerical Rating Scale (WI-NRS) from baseline to week 24, and an Investigator’s Global Assessment for PN stage (IGA PN-S) score of 0/1 (clear/almost clear) at week 24. Safety outcomes included the incidence of treatment-emergent adverse events (TEAEs). Among patients with PN, 8.0% reported prior use of phototherapy, and 36.7% reported prior use of IS; overall, 126 (dupilumab group, n = 62; placebo group, n = 64) patients with and 185 (dupilumab, n = 91; placebo, n = 94) patients without prior IS/phototherapy use were included. A larger proportion of patients with prior treatment vs. patients without prior treatment had severe disease, as measured by IGA PN-S (40.5% vs. 29.0%). The baseline WI-NRS score (SD) for overall patients with prior treatment was 8.6 (1.0) and for patients without prior treatment was 8.4 (1.0). At week 24, 67.7% vs. 15.6% of patients in the dupilumab vs. placebo groups with prior treatment (odds ratio [95% confidence interval]: 13.6 [3.7–49.7]; P < 0.0001), and 52.7% vs. 21.3% of patients without prior treatment (5.8 [2.4–14.0]; P < 0.0001) achieved improvement in WI-NRS. Similarly, 35.5% vs. 10.9% (3.1 [1.2–8.4]; P = 0.0162) of patients with and 53.8% vs. 21.3% (5.0 [2.3–10.8]; P < 0.0001) of those without prior treatment achieved IGA PN-S score of 0/1, respectively. TEAEs were reported by 43 (69.4%) vs. 34 (53.1%) patients (dupilumab vs. placebo groups) with and 54 (60.0%) vs. 55 (59.1%) without prior treatment, respectively. Patients treated with dupilumab experienced a greater and clinically meaningful improvement in itch and achieved skin that was clear/almost clear of nodules at week 24, regardless of prior use of IS/phototherapy for the treatment of PN. The incidence of TEAEs was generally consistent among patients with and without prior IS/phototherapy.

An international, multicenter, observational survey to evaluate diabetes control in subjects using insulin for the treatment of type 1 and type 2 diabetes mellitus in the Czech Republic and Slovak Republic: study protocol for a cross-sectional survey Jan Brož,1 Denisa Janickova Zdarska,1 Jana Urbanova,2 Marek Brabec,3 Bohumila Krivska,4 Viera Donicova,5 Radka Stepanova,6 Emil Martinka,7 Milan Kvapil1 1Department of Internal Medicine, Second Faculty of Medicine, 2Center for Research on Diabetes, Metabolism and Nutrition, Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, 3Institute of Computer Science of the ASCR, vvi, 4Sanofi, Prague, Czech Republic; 5Private Department of Diabetology, Internal Medicine and Metabolism, Kosice, Slovak Republic; 6ADDS sro, Brno, Czech Republic; 7National Institute of Endocrinology and Diabetology, Lubochna, Slovak Republic Background: Despite the improvements in insulin therapy, a large number of patients fail to achieve their target glycated hemoglobin (HbA1c) levels. Control of diabetes is often unsatisfactory because the patient does not know about the principles of successful insulin therapy (ie, blood glucose self-monitoring, the principles of insulin administration, titration, current dose adjustments, dietary recommendations, and physical activity preventive measures) or because these principles are applied incorrectly or insufficiently. Furthermore, the fear of hypoglycemia may lead to maintaining higher than recommended blood glucose levels. Methods/design: This is a noninterventional, international study focusing on a questionnaire survey of diabetes patients (patient-reported outcome) treated with insulin for at least 1 year. It is designed so that the data obtained reflect real access of patients to insulin treatment. The primary objective is to show the results of glycemic control of diabetes (HbA1c) achieved in diabetes patients treated with at least one dose of insulin. The secondary objective is to monitor the factors potentially affecting these results, which include the frequency and other characteristics of hypoglycemia, the frequency of blood glucose self-monitoring, and the effects produced when the results are employed in adjusting the therapy. Furthermore, the study investigates factors related to the principles of insulin administration, dietary regime, and exercise habits. The study will enroll a total of 1,500 patients with type 1 and type 2 diabetes in 150 centers: two-thirds in the Czech Republic and one-third in the Slovak Republic. Discussion: The study is primarily aimed at determining the percentage of insulin-treated diabetes patients reaching the recommended targets for glycemic control (HbA1c). Furthermore, it attempts to identify and describe in detail the factors of failure in achieving the therapeutic goals. An analysis of the data thus obtained may result in recommendations on how to reduce and eliminate all the identified negative factors in the future. Keywords: insulin therapy, glycemic control, HbA1c, hypoglycemia, education, diabetes regimen adherence

Abstract This new design of potentiometric sensor involves 4‐mercaptophenylboronic acid (MPBA) evaporated onto a gold layer sputtered onto the surface of a plasticized poly(vinyl chloride) membrane based on a pH indicator. Fourier‐transform infrared spectroscopy confirms the presence of the pH indicator in close contact with the sputtered gold layer, and the covalent fixing of MPBA molecules onto this gold layer. The changes in pH resulting from the interaction between MBPA and the model saccharide (glucose) are reflected in the changes in the membrane capacitance and the potentiometric signal. The potentiometric sensor responds over the concentration range from 0.3 to 29.7 mM glucose.