This is a randomised, double-blind, placebo-controlled, cross-over phase 2 trial investigating the effect of C21 on cold-induced vasoconstriction in subjects with Raynaud's phenomenon secondary to systemic sclerosis. The purpose of the trial is to achieve a vasodilatory effect in subjects with Raynaud's phenomenon by stimulation of the AT2R (angiotensin II type 2 receptor) with C21.

Inclusion Criteria:

1. Written informed consent must be obtained before any trial related procedures are performed.
2. Subjects diagnosed with SSc according to European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria
3. Age 19-75 years inclusive
4. 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:

1. Smoking (including E-cigarettes) or use of nicotine replacement therapy for three months prior to Visit 1 and during the trial.

2. BMI >30

3. Mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease).

4. 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

5. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma and cervical intraepithelial neoplasia grade I

6. Planned major surgery within the duration of the study

7. 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)

8. Blood donation (or corresponding blood loss) within three months prior to Visit 1

9. 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

10. 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

11. Pregnant or breast-feeding female subjects.

12. Female subjects of childbearing potential not willing to use contraceptive methods described in Section 5.3.1.

13. Male subjects not willing to use contraceptive methods described in Section 5.3.1.

14. Participation in any other interventional trial during the trial period

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)

From signing of informed consent through study completion, an average of 30 days

At each visit the subject was asked about adverse events (AEs) in an objective manner, e.g.: "Have you experienced any problems since the last visit?"

The study will be conducted in double-blind fashion and the allocation of treatments will not be disclosed until clean file has been declared and the database has been locked.