PMID- 37300792 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230629 IS - 2193-8210 (Print) IS - 2190-9172 (Electronic) VI - 13 IP - 7 DP - 2023 Jul TI - Safety and Efficacy of a Novel Combination Cream (GN-037) in Healthy Volunteers and Patients with Plaque Psoriasis: A Phase 1 Trial. PG - 1489-1501 LID - 10.1007/s13555-023-00939-7 [doi] AB - INTRODUCTION: Psoriasis 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. METHODS: A 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. RESULTS: A 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. CONCLUSION: The 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). TRIAL REGISTRATION NUMBER: NCT05428202. CI - (c) 2023. The Author(s). FAU - Sezer, Zafer AU - Sezer Z AD - Department of Pharmacology, Faculty of Medicine, Erciyes University, Kayseri, Turkey. AD - Hakan Cetinsaya Good Clinical Practice and Research Centre (IKUM), Erciyes University, Kayseri, Turkey. FAU - Inal, Ahmet AU - Inal A AD - Department of Pharmacology, Faculty of Medicine, Erciyes University, Kayseri, Turkey. AD - Hakan Cetinsaya Good Clinical Practice and Research Centre (IKUM), Erciyes University, Kayseri, Turkey. FAU - Cinar, Salih L AU - Cinar SL AD - Department of Dermatology, Faculty of Medicine, Erciyes University, Kayseri, Turkey. FAU - Mazicioglu, Mustafa M AU - Mazicioglu MM AD - Department of Family Medicine, Faculty of Medicine, Erciyes University, Kayseri, Turkey. FAU - Altug, Sedat AU - Altug S AD - Department of Pharmacology, Faculty of Medicine, Demiroglu Bilim University, Istanbul, Turkey. FAU - Karasulu, Hatice Y AU - Karasulu HY AD - Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, Izmir, Turkey. AD - Center for Drug R&D and Pharmacokinetic Applications (Argefar), Ege University, Izmir, Turkey. FAU - Diril, Mine AU - Diril M AD - Department of Research and Development, Sedef Ilac ve Medikal Urunleri Ind. Trade. Co. Ltd., Kastamonu, Turkey. FAU - Mehmetoglu Al, Ayca AU - Mehmetoglu Al A AD - Department of Research and Development, Sedef Ilac ve Medikal Urunleri Ind. Trade. Co. Ltd., Kastamonu, Turkey. FAU - Kozlu, Serhat AU - Kozlu S AD - Department of Research and Development, Gen Ilac ve Saglik Urunleri A.S., ASO 2. ve 3. Organize Sanayi Bolgesi, Alci OSB Mahallesi, 2013. Cadde, No: 24, 06930, Sincan, Ankara, Turkey. FAU - Ulu, Nadir AU - Ulu N AUID- ORCID: 0000-0002-2681-8615 AD - Department of Research and Development, Gen Ilac ve Saglik Urunleri A.S., ASO 2. ve 3. Organize Sanayi Bolgesi, Alci OSB Mahallesi, 2013. Cadde, No: 24, 06930, Sincan, Ankara, Turkey. n.ulu@genilac.com. LA - eng SI - ClinicalTrials.gov/NCT05428202 SI - ClinicalTrials.gov/NCT05706870 SI - ClinicalTrials.gov/NCT05428202 GR - 5180004/TUBITAK/ PT - Journal Article DEP - 20230610 PL - Switzerland TA - Dermatol Ther (Heidelb) JT - Dermatology and therapy JID - 101590450 PMC - PMC10256958 OTO - NOTNLM OT - GN-037 OT - Phase 1 OT - Plaque psoriasis OT - Topical treatment COIS- Nadir Ulu and Serhat Kozlu report employment on Gen Ilac ve Saglik Urunleri A.S. Mine Diril and Ayca Mehmetoglu report employment on Sedef Ilac ve Medikal Urunleri Ind. Trade. Co. Ltd. Other authors declared that they have no potential conflicts of interest with respect to the investigation, authorship, and/or publication of this article. EDAT- 2023/06/10 23:42 MHDA- 2023/06/10 23:43 PMCR- 2023/06/10 CRDT- 2023/06/10 11:18 PHST- 2023/04/13 00:00 [received] PHST- 2023/05/09 00:00 [accepted] PHST- 2023/06/10 23:43 [medline] PHST- 2023/06/10 23:42 [pubmed] PHST- 2023/06/10 11:18 [entrez] PHST- 2023/06/10 00:00 [pmc-release] AID - 10.1007/s13555-023-00939-7 [pii] AID - 939 [pii] AID - 10.1007/s13555-023-00939-7 [doi] PST - ppublish SO - Dermatol Ther (Heidelb). 2023 Jul;13(7):1489-1501. doi: 10.1007/s13555-023-00939-7. Epub 2023 Jun 10.