Safety and Efficacy of a Novel Combination Cream (GN-037) in Healthy Volunteers and Patients with Plaque Psoriasis: A Phase 1 Trial

IntroductionPsoriasis is a common skin disorder associated with physical and psychological burdens. Visible disfiguration can trigger a negative reaction which can cause much of the readily measurable psychological burden of the disease. Although many biological treatments provide some success in the initial clearance of lesions, there is a dispute about the long-term maintenance of the disease, as no current biological treatment has been shown to be curative. Topical therapies are still the most widely used agents as first-line and maintenance treatment for psoriasis. The present study aimed to investigate the safety, tolerability, and, to some extent, efficacy of GN-037 cream in patients with psoriasis and healthy volunteers.MethodsA randomized, double-blind, single-center, placebo-controlled phase 1 clinical study was conducted to evaluate the safety, tolerability, and clinical efficacy of GN-037 cream topically applied twice daily for 2 weeks in healthy subjects (n = 12) and patients (n = 6) diagnosed with plaque-type psoriasis. Six healthy subjects received placebo. Patients with plaque psoriasis were evaluated by a dermatologist, and Physician Global Assessment (PGA) score was required to be >= 3 (moderate psoriasis) at screening.ResultsA total of 31 adverse events (AEs) occurred in 13 participants during the study: 9 AEs in healthy subjects receiving GN-037 cream, 3 AEs in healthy subjects receiving placebo, and 1 AE in one psoriatic patient. The most frequently reported AEs were reactions at the application site, including erythema, exfoliation, pruritus, and burning sensation. During the baseline evaluation, one patient had a PGA score of 3 (moderate) and five patients had a PGA score of 4 (severe). On day 14, in treatment, four patients experienced second grade and two patients third grade improvements compared with baseline, indicating a shift of patients from moderate and severe disease to mild disease and to almost clear (score 2 or 1). There were slight increases in plasma tumor necrosis factor (TNF)-alpha, interleukin-17 (IL-17) and interleukin-23 (IL-23) levels in both healthy volunteers and patients throughout the study, as compared with baseline.ConclusionThe results of this phase 1 trial conducted in 18 healthy volunteers and 6 patients with plaque psoriasis demonstrated a favorable safety and tolerability profile for GN-037; therefore, further clinical development of GN-037 in a phase 2 clinical trial has been initiated in patients with mild to moderate plaque psoriasis (NCT05706870).This study was sponsored by Gen Ilalve Saglik Urunleri A.S. and partially supported by a research grant from The Scientific and Technological Research Council of Turkey [TUBITAK 1505, grant number: 5180004]. The journal's Rapid Service Fee is funded by Gen Ilalve Saglik Urunleri A.S.Gen Ilalve Saglik Urunleri A.S.; Scientific and Technological Research Council of Turkey [TUBITAK 1505, 5180004

Experimental assessment of methods of dissemination of the thermodynamic temperature at the highest temperatures

In the frame of the European Metrology Research Programme (EMRP)-funded joint research project “Implementing the new kelvin” one work package is devoted to the assessment of two different methods of dissemination of the thermodynamic temperature. These two methods are the dissemination via high temperature fixed points (HTFP) with assigned thermodynamic temperatures and the dissemination by radiometers or radiation thermometers calibrated in terms of thermodynamic temperature. To achieve a thorough assessment of these two distinct dissemination methods two dissemination exercises were organised in the form of comparisons. In one case the circulating artefacts were off-the-shelf high-temperature fixed point cells with transition temperatures ranging from 1324 °C to 2474 °C, in the other case absolutely calibrated pyrometers and filter radiometers were compared in the temperature range 1000 °C to 2500 °C. This work showed that both schemes were achievable with competing advantages and drawbacks and would most probably help disseminating thermodynamic temperature in the future at the level of 1 K to 2 K uncertainty over the whole temperature range