Safety and Tolerability of TOP-N53 Applied on Digital Ulcers in Patients With Systemic Sclerosis

The main goal of this clinical trial is to learn about how safe the new drug TOP-N53 solution is when it is applied to open wounds on the fingertip (digital ulcers) in people with an uncommon illness that results in hard, thickened areas of skin and additional problems with internal organs and blood vessels (systemic sclerosis). Another goal is to learn if different strengths of TOP-N53 can treat certain aspects of the illness. Men and women between 18 and 69 years of age with this illness may participate in the clinical trial. A parallel treatment with Sildenafil 20 mg is allowed for clinical trial participants. The main questions the clinical trial aims to answer are: * Does TOP-N53 cause medical problems at the fingertip wound after it is directly applied to the wound? * Does TOP-N53 affect certain aspects of the illness like blood flow in the fingertip wounds, itch, pain, redness, bruises and bleeding at or beyond the fingertip wounds? Researchers will compare TOP-N53 solution in different strengths to a placebo (a look-alike substance that contains no drug) to see if TOP-N53 works to affect the aspects of the illness listed above. Participants will receive one or two treatments with the placebo or different strengths of TOP-N53. The higher strength of the drug will only be given to participants after the lower strength was found to be safe. Participants will visit the clinic up to 8 times within a maximum of 31 days. 2 visits may be done by telephone. The doctors will ask questions to ensure that it is safe for the participants to be in the clinical trial, apply the drug and follow-up on any medical problem after the treatment. They will also test if the drug works to treat the illness by several test methods before and after the treatment. Participants will help to find out whether the drug works to treat the illness and is safe by answering questions in a diary at different timepoints before and after treatment.

Inclusion Criteria: 1. Participants who are able to understand and follow instructions during the clinical trial. 2. Signed written informed consent in accordance with ICH-GCP and local legislation prior to admission to the clinical trial. 3. Male or female participants aged ≥18 years of age at screening (V0) with SSc, limited or diffuse cutaneous, according to 2013 American College of Rheumatology (ACR)/EULAR criteria (\*sex refers to biological characteristics). 4. At least one active DU, considered as the cardinal DU, due to SSc, ≥2 mm in diameter at screening (V0) and baseline (V1/V1b) with at least an involvement of the dermis, located at the interphalangeal fingertip or on the volar surface distal to the proximal joint. 5. Participants meeting one of the following 2 criteria: 1. On stable PO sildenafil treatment at 20 mg TID \[3 times per day\] for at least 2 weeks prior screening (V0). 2. Not on any PO PDE5 inhibitor (sildenafil, tadalafil, vardenafil, mirodenafil) or unselective PDE inhibitors (theophylline, dipyridamole) at any dose (including for recreational purposes) for at least 4 weeks prior screening (V0). 6. The physical examination must be without disease findings except SSc unless the investigator considers an abnormality to be irrelevant to the outcome of the clinical trial (screening \[V0\] and baseline \[V1/V1b\]). 7. Concomitant medication as endothelin receptor antagonists, calcium channel blockers, and antiplatelets must have been used at stable doses at least 2 weeks prior to screening (V0), if applicable. 8. Female volunteers of childbearing potential1 must either be permanently sterile or agree to use a highly effective birth control method (failure rate ˂1% per year when used consistently and correctly) throughout the clinical trial and for at least 7 weeks after last administration of IP. 9. A male participant with a female partner of childbearing potential1 must agree to use adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice). 10. Covered by health insurance system and/or in compliance with the recommendations of national law in force relating to biomedical research. Exclusion Criteria: 1. Any DU accompanied by one of the following complications: Clinical infection of active ulcer/peri-ulcer, osteitis, gangrene (screening \[V0\] and baseline \[V1/V1b\]). 2. Participants with modified Rodnan Skin Score (mRSS) \>35 (screening \[V0\]). 3. Intractable pain from DUs (NRS ≥6) (screening \[V0\] and baseline \[V1/V1b\]). 4. Active or previous history of calcinosis at the site of the designated cardinal DU. 5. Unstable organ manifestations of SSc that require immediate medical attention and treatment e.g., scleroderma renal crisis, or where other organ manifestations of SSc (interstitial lung disease \[ILD\], pulmonary hypertension, gastrointestinal with malabsorption syndrome or bleeding, symptomatic primary myocardial involvement) are poorly controlled and/or are determinants of clinical symptomatology. 6. Any documented active or suspected malignancy or history of malignancy within 5 years prior to the screening visit (V0), except appropriately treated basal cell carcinoma of the skin, actinic keratoses, "under surveillance" prostate cancer or in situ carcinoma of uterine cervix. 7. Participants with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment). 8. Participants with a significant disease or condition other than SSc which in the opinion of the investigator, may put the participant at risk because of participation, interfere with clinical trial procedures, or cause concern regarding the participant's ability to participate in the clinical trial or any medical condition which is expected to lead to a life expectancy \