a study to investigate safety of gs-248 and efficacy on raynauds' phenomenon in systemic sclerosis

Conditions: Systemic Sclerosis

Summary: the primary objective of this study is to determine the safety, and evaluate the efficacy of gs-248 versus placebo on raynaud's phenomenon (rp) in subjects with systemic sclerosis (ssc).

the primary objective of this study is to determine the safety, and evaluate the efficacy of gs-248 versus placebo on raynaud's phenomenon (rp) in subjects with systemic sclerosis (ssc). this is a randomized, double-blind, placebo-controlled study conducted in multiple sites in 4 countries in europe. approximately 80 subjects will be randomized in a 1:1 allocation to receive either gs-248 (120 mg) or placebo once daily. the study will comprise an enrolment period, a treatment period, and a follow-up period, with a total of 5 study visits over approximately 10 weeks.

Eligibility criteria:
inclusion criteria: * subjects must provide signed and dated written informed consent before the conduct of any study-specific procedures. * male and female subjects aged 18-75 years inclusive. * systemic sclerosis diagnosed according to european league against rheumatism (eular)/american college of rheumatology (acr) criteria (van den hoogen f et al. 2013). subjects with signs of other autoimmune diseases (e.g. sjögren's syndrome, myositis, rheumatoid arthritis) could be included if ssc is the dominating phenotype. * raynaud attacks typically ≥7 times per week during the last 4 weeks prior to screening despite background medication (only allowed vasodilatory therapy is calcium channel blockers or pde-5 inhibitors). * women of childbearing potential must be using a highly effective method of contraception to avoid pregnancy throughout the study and for 4 weeks after the last dose of investigational medicinal product in such manner that the risk of pregnancy is minimised. * women must not be pregnant or breastfeeding. * male subjects to agree to use condom in combination with use of contraceptive methods with a failure rate of \<1% to prevent pregnancy and drug exposure of a partner, and refrain from donating sperm from the first date of dosing until 3 months after last dosing of the imp. * ability of subjects to participate fully in all aspects of this clinical trial. exclusion criteria: * systemic sclerosis disease duration of greater than 120 months from first non-raynaud manifestation * current smokers or stopped smoking \<3 months prior to visit 1. * dose-change or initiation of vasodilating substances (calcium blockers or pde-5 inhibitors) within 4 weeks prior to visit 1. * use of iloprost or other intravenous (iv) or po prostacyclin receptor agonist within 4 weeks prior to visit 1. * ongoing treatment with immunosuppressive therapies (other than mycophenolate) including, but not restricted to; cyclophosphamide, azathioprine, methotrexate, or cyclosporine, or use of those medications within 4 weeks of trial entry. * use of systemic corticosteroids during 4 weeks before screening and during the course of the study. * concurrent serious medical condition, with special attention to cardiovascular conditions, which in the opinion of the investigator makes the subject not suitable for this study. * prolonged qtcf interval defined as a mean qtcf \>450 msec. * creatinine clearance \<50 ml/min (determined by cockcroft-gault equation) at screening. * active digital ulcer (du) within 4 weeks prior to visit 1. * clinically meaningful laboratory abnormalities at screening (visit 1), as determined and documented by the investigator.