Cold Challenge With C21 in RP

Inclusion criteria

• Written informed consent must be obtained before any trial related procedures are performed.
• Subjects diagnosed with SSc according to European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria
• Age 19-75 years inclusive
• RP secondary to SSc as determined by the investigator, and with a typical frequency of attacks during the winter months (November-March) of on average at least 5 per week.

Exclusion criteria

• Smoking (including E-cigarettes) or use of nicotine replacement therapy for three months prior to Visit 1 and during the trial.
• BMI >30
• Mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease).
• Concurrent serious medical condition with special attention to cardiac or ophthalmic conditions which in the opinion of the investigator makes the patient inappropriate for this study
• Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma and cervical intraepithelial neoplasia grade I
• Planned major surgery within the duration of the study
• Subjects who forsake any alcohol intake or have known uncontrolled allergic conditions or allergy/hypersensitivity to any components of the trial drug or placebo excipients (see Section 7.1)
• Blood donation (or corresponding blood loss) within three months prior to Visit 1
• Treatment with any of the medications listed below within 4 weeks prior to Visit 1:

• Any dose-change or initiation of vasoactive substances

, and not able or willing to withhold these medications for 3 days preceding Visit 2 and Visit 3, respectively

• Iloprost
• Any treatment with CYP3A4 inducers (e.g. rifampicin, phenytoin, St John's Wort)
• Any treatment with CYP3A4 inhibitors (e.g. clarithromycin, ketoconazole, nefazodone, itraconazole, ritonavir)
• Any treatment with medicines that are substrates of CYP1A2, CYP3A4 or CYP2C9 with a narrow therapeutic range
• Any experimental drug
• Any systemic immunosuppressive therapy other than:

• Inhaled corticosteroids which can be used throughout the trial period
• The continuation of stable doses of <10 mg prednisolone
• Mycophenolate mofetil (MMF) which must be withheld for 3 days preceding Visit 2 and Visit 3
• Any of the following findings at the time of screening:

• Finger temperature below 27°C after acclimatising at an ambient temperature of 23°C for a period of 20 minutes
• Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG, as judged by the Investigator
• Positive results for HBsAg, HCVAb or HIV 1+2 Ag/Ab
• Positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
• Clinically significant abnormal laboratory value at Visit 1 indicating a potential risk for the subject if enrolled in the trial as evaluated by the Investigator
• Pregnant or breast-feeding female subjects.
• Female subjects of childbearing potential not willing to use contraceptive methods described in Section 5.3.1.
• Male subjects not willing to use contraceptive methods described in Section 5.3.1.
• Participation in any other interventional trial during the trial period
• Subjects known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder)