AB0855 BASELINE DEMOGRAPHICS AND DISEASE CHARACTERISTICS IN A PHASE 2 STUDY TO EVALUATE EFFICACY, SAFETY, AND TOLERABILITY OF MT-7117 IN SUBJECTS WITH DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS

• Published in: Annals of the rheumatic diseases Vol. 82; no. Suppl 1; pp. 1640 - 1641
• Main Authors: Khanna, D., Carreira, P., Chung, L., Denton, C. P., Matucci-Cerinic, M., Riemekasten, G., Mukai, S., Liu, S., Cai, S., Bogoslovsky, T.
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2023; Elsevier Limited
• Subjects: Age; Autoantibodies; Azathioprine; Clinical trials; Demographics; Demography; DNA-directed RNA polymerase; Endothelial cells; Fibrosis; Hydroxychloroquine; Immunological tolerance; Immunosuppressive agents; Inflammation; Melanocortin; Melanocyte-stimulating hormone; Methotrexate; Mycophenolic acid; Placebos; Randomized control trial; Rare/orphan diseases; Rheumatology; RNA polymerase; Scientific Abstracts; Scleroderma; Systemic sclerosis; Poland; North America; Europe
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2023-eular.4003

BackgroundDersimelagon (MT-7117), a novel synthetic, oral, selective melanocortin-1 receptor agonist, demonstrated disease-modifying effects in preclinical models of systemic sclerosis (SSc). MT-7117 reduces inflammation, vascular dysfunction, and fibrosis through its pleiotropic effects on inflammatory cells, endothelial cells, and fibroblastsis, and is as a potential therapeutic agent for the treatment of SSc. A phase 2 proof of concept clinical trial (MT-7117-G02) in subjects with diffuse cutaneous SSc (dcSSc) is ongoing (NCT04440592). 73 subjects (target 72) were enrolled over 22 months at 33 sites in 8 countries.ObjectivesEvaluate the demographics, baseline disease characteristics and the standard of care of the subjects randomized in MT-7117-G02 study to examine variability of these parameters by the geographic regions (North America [NA], Europe [excluding Poland], and Poland). Population in Poland was analyzed separately due to delayed inclusion in the study and the highest enrollment rate.MethodsMT-7117-G02 is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, 52-week parallel-group study to evaluate the efficacy, safety, and tolerability of MT-7117 in subjects with dcSSc. Eligible subjects were randomized 1:1 to either MT-7117 QD or matching placebo and stratified by the autoantibody status of anti-RNA Polymerase III at screening (positive or negative). The primary endpoint is the American College of Rheumatology Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (ACR CRISS) composite score at Week 52. The study included subjects who have been diagnosed with dcSSc ≥ 18 years of age and a disease duration ≤ 5 years who are on a stable standard of care treatment, receiving one stable concomitant immunosuppressant (Mycophenolate/Mycophenolic acid [MMF], Methotrexate [MTX], Hydroxychloroquine [HCQ], or Azathioprine [AZA]). Eligibility included the baseline Modified Rodnan skin score (mRSS) of 15-45 units and Forced Vital Capacity (FVC%) predicted > 50%.ResultsMost of enrolled subjects were middle-aged White females and approximately half received one immunosuppressant (Table 1). MMF was the most frequently used immunosuppressant followed by MTX. Approximately ¾ of the subjects had normal CRP with comparable distribution across the regions. There were neither regional differences in the baseline mRSS nor in the predicted FVC%. The overall average frequency of anti-RNA Polymerase III antibody positivity was 20.5%, with the lowest proportion in Poland (15.4%). The average frequency of anti-Scl-70 positivity was 50.7% with the lowest proportion in NA (23.5%). Subjects in NA were more likely to be on MMF.Table 1: Baseline demographics and disease characteristics by Regions (Blinded)Mean (SD) or n (%)OverallNorth America*Europe†PolandNumber73 (100 %)17 (23.3 %)30 (41.1 %)26 (35.6 %)Age (yrs)51.6 ± 12.454.7 ± 12.552.2 ± 10.648.9 ± 14.2Disease duration (yrs)2.0 ± 1.41.7 ± 1.41.9 ± 1.32.2 ± 1.6Female55 (75.3 %)15 (88.2 %)22 (73.3 %)18 (69.2 %)White65 (89.0 %)11 (64.7 %)28 (93.3 %)26 (100 %)Anti-RNA-Poly III positive15 (20.5 %)4 (23.5 %)7 (23.3 %)4 (15.4 %)Anti- Scl-70 positive37 (50.7 %)4 (23.5 %)16 (53.3 %)17 (65.4 %)Normal CRP (≤ 5.0 mg/L)58 (79.5 %)13 (76.5 %)22 (73.3 %)23 (88.5 %)Any immunosuppressant‡41 (56.2 %)10 (58.8 %)17 (56.7 %)14 (53.8 %)MMF24 (32.9 %)7 (41.2 %)9 (30.0 %)8 (30.8 %)MTX14 (19.2 %)1 (5.9 %)7 (23.3 %)6 (23.1 %)HCQ7 (9.6 %)1 (5.9 %)4 (13.3 %)2 (7.7 %)AZA2 (2.7 %)1 (5.9 %)1 (3.3 %)0mRSS (0-51)24.8 ± 7.923.1 ± 9.225.3 ± 7.925.2 ± 7.2FVC% predicted88.0 ± 17.988.7 ± 20.282.0 ± 16.994.4 ± 15.5*US and Canada† UK, Germany, Spain, Italy, and Belgium‡ Includes MMF, MTX, HCQ, and AZAConclusionThere were no major differences in the baseline demographics such as disease duration, sex and age, and no major differences in disease severity as well as the percentage of use of immunosuppressants among the regions although some variation in SSc autoantibody specificity were observed.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsDinesh Khanna Shareholder of: Eicos Sciences, Inc - stocks, Consultant of: AbbVie, Acceleron, Actelion, Amgen, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, Genentech/Roche, Gilead, GlaxoSmithKline, Horizon Therapeutics, Merck Sharp & Dohme, Mitsubishi Tanabe, Sanofi-Aventis, United Therapeutics, Prometheus, Theraly, AstraZeneca, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health, Pfizer, Employee of: CiviBioPharma/Eicos Sciences, Inc - Leadership/Equity position – Chief Medical Officer, Patricia Carreira Consultant of: Janssen, Lilly, VivaCell, Emerald Health Pharmaceuticals, Gesynta Pharma, Boehringer Ingelheim, Abbie, Sanofi Genzyme, Mitsubishi Tanabe, Lorinda Chung Consultant of: Mitsubishi Tanabe, Eicos Sciences, Genentech, Kyverna and Jannsen, Grant/research support from: Boerhinger Ingelheim, Christopher P Denton Speakers bureau: Janssen, Boehringer Ingelheim, Consultant of: GSK, Boehringer Ingelheim, CSL Behring, Corbus, Roche, Gesynta, Mitsubishi Tanabe, Grant/research support from: Servier, GSK, Arxx Therapeutics, Horizon, Marco Matucci-Cerinic Consultant of: Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi Tanabe, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Gabriela Riemekasten Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Mitsubishi Tanabe, sakiko mukai Employee of: Mitsubishi Tanabe, Shawn Liu Employee of: Mitsubishi Tanabe, Songjie Cai Employee of: Mitsubishi Tanabe, Tanya Bogoslovsky Employee of: Mitsubishi Tanabe.