Raynaud's phenomenon (RP) in patients with Systemic sclerosis (SSc) MedDRA version: 20.0 Level: LLT Classification code 10037917 Term: Raynauds System Organ Class: 100000004866 MedDRA version: 21.0 Level: LLT Classification code 10042953 Term: Systemic sclerosis System Organ Class: 100000004859
Conditions
Sponsors
Gesynta Pharma AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must provide signed and dated written informed consent before the conduct of any study-specific procedures. 2. Male and female subjects aged 18-75 years inclusive. 3. SSc 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. 4. 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). 5. Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and for 4 weeks after the last dose of IMP in such manner that the risk of pregnancy is minimised.* 6. Women must not be pregnant or breastfeeding. 7. Male subjects to agree to use condom in combination with use of contraceptive methods with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. SSc disease duration of greater than 120 months from first non-Raynaud manifestation 2. Current smokers or stopped smoking or used nicotine in any form 450 msec at Visit 1, or at Visit 2 (prior randomisation). 10. Creatinine clearance <50 mL/min (determined by Cockcroft-Gault equation). 11. Active digital ulcer (DU) within 4 weeks prior to Visit 1. 12. Have known allergies to any components of the GS-248 formulation. 13. Clinically meaningful laboratory abnormalities at Screening (Visit 1), as determined and documented by the Investigator. 14. Positive test results for HBsAg, HCVAb or HIV-1 and/or -2 antibodies at Screening (Visit 1). 15. Subjects known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder). 16. Subject is mentally or legally incapacitated at the time of screening or has a history of clinically significant psychiatric disorders that would impact the subject’s ability to participate in the study according to the Investigator. 17. Malignancy within the past 5 years except for in situ removal of basal cell carcinoma and cervical intraepithelial neoplasia grade I. 18. Planned major surgery within the duration of the study. 19. Blood donation (or corresponding blood loss) within 12 weeks prior to Visit 1. 20. Participation in another interventional clinical study involving IMP within 4 weeks or given an experimental drug within 5 half-lives, whichever longest, prior to Visit 1. Exclusion Criterion for Cold Challenge At Visit 2: Finger temperature below 27°C after acclimatising at an ambient temperature of 23°C (±2°C) for a period of 20 minutes. Randomization Criteria: In addition to fulfilling all inclusion and exclusion criteria, subjects must fulfil the following criteria to be randomised: 1. =7 RP attacks during the last week of the run-in period as captured in the eDiary, with no more than 2 days without RP attacks. 2. Compliance with the eDiary during the 7 most recent days prior to baseline (Vi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and efficacy of GS-248 versus placebo on RP in subjects with SSc.;Secondary Objective: To determine the efficacy of GS-248 on peripheral vascular blood flow in patients with SSc.;Primary end point(s): Primary efficacy endpoint: Mean change from baseline to week 4 in the number of Raynaud’s Phenomenon attacks per week. Primary safety endpoints: • Incidence of Adverse events • Incidence of Serious Adverse Events • Clinical laboratory and vital signs.;Timepoint(s) of evaluation of this end point: Baseline to week 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary efficacy endpoints: Mean change from baseline to week 4 in the Raynaud’s Condition Score (RCS) Mean change from baseline to week 4 in the cumulative duration of Raynaud’s Phenomenon attacks Mean change from baseline to week 4 in pain experienced during RP attacks Other secondary endpoints: Mean change from baseline to week 4 in peripheral blood flow prior to cold challenge and IMP administration. Mean change from baseline to week 4 in peripheral blood flow from pre-IMP, to post-IMP administration at Visit 2. Mean change in recovery of peripheral blood flow after cold challenge from pre-IMP to post-IMP administration at Visit 2 Mean change from baseline to week 4 in recovery of peripheral blood flow after cold challenge. ;Timepoint(s) of evaluation of this end point: Efficacy endpoints: Baseline to week 4 Other endpoints: Week 2 and week 4 | — |
Countries
Netherlands, Poland, United Kingdom
Contacts
Public ContactClinical Information Point
Gesynta Pharma AB
Outcome results
None listed