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

NCT06954597 | Recruiting Phase 2

• 2 other identifiers: TOP-N53-022024-511861-12-00
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

Digital Ulcers in Systemic Sclerosis

Keywords

digital ulcer; systemic sclerosis; safety; PDE5 inhibitor

Outcome Measures

Primary Outcomes (2)

• Local treatment emergent adverse events (TEAEs)

  Frequency of local TEAEs from treatment initiation until follow-up (FU) visit

  From first treatment until Follow-up visit; up to 37 days

• Investigator-solicited digital ulcer (DU)-related patient reported outcome (DU-PRO) - Pain

  Frequency and mean score of pain (actual) at the cardinal DU as assessed by using a numeric rating scale (NRS, graduating intensity from 0 \['no pain'\] to 10 \['worst imaginable pain'\]).

  Per dose/time escalation step at screening, at treatment days prior and several times after treatment as well as on follow-up visits during a maximum time period of 37 days.

Secondary Outcomes (8)

• Clinical digital ulcer (DU) assessment (CDUA) endpoint - erythema at the peri ulcer area of the cardinal DU

  Per dose/time escalation step at screening, at treatment days prior and several times after treatment as well as on follow-up visits during a maximum time period of 37 days.

• Clinical digital ulcer (DU) assessment (CDUA) endpoint - bruising at the peri-ulcer area of the cardinal DU or beyond

  Per dose/time escalation step at screening, at treatment days prior and several times after treatment as well as on follow-up visits during a maximum time period of 37 days.

• Clinical digital ulcer (DU) assessment (CDUA) endpoint - hemorrhage in the cardinal DU

  Per dose/time escalation step at screening, at treatment days prior and several times after treatment as well as on follow-up visits during a maximum time period of 37 days.

• Clinical digital ulcer (DU) assessment (CDUA) endpoint - perilesional newly emerging, wound related edema at the cardinal DU

  Per dose/time escalation step at screening, at treatment days prior and several times after treatment as well as on follow-up visits during a maximum time period of 37 days.

• Clinical digital ulcer (DU) assessment (CDUA) endpoint - clinical infection at the cardinal DU

  Per dose/time escalation step at screening, at treatment days prior and several times after treatment as well as on follow-up visits during a maximum time period of 37 days.

Study Arms (5)

Treatment step 1

PLACEBO COMPARATOR

Treatment with vehicle (= 0 µg TOP-N53), 3h exposure

Drug: Sildenafil; Drug: TOP-N53 vehicle

Treatment Step 2

EXPERIMENTAL

Treatment with 2 µg TOP-N53, 3h exposure

Drug: TOP-N53; Drug: Sildenafil

Treatment step 3

EXPERIMENTAL

Treatment with 4 µg TOP-N53, 3h exposure

Drug: TOP-N53; Drug: Sildenafil

Treatment step 4

EXPERIMENTAL

Treatment with 8 µg TOP-N53, 3h exposure

Drug: TOP-N53; Drug: Sildenafil

Treatment step 5

EXPERIMENTAL

Treatment with 8 µg TOP-N53, 24h exposure

Drug: TOP-N53; Drug: Sildenafil

Interventions

TOP-N53 DRUG

TOP-N53 solution (IMP) containing 80 µg/ml TOP-N53 is applied topically directly to the digital ulcer of patients with systemic sclerosis. The dose if defined by volume and exposure time of the IMP.

Treatment Step 2; Treatment step 3; Treatment step 4; Treatment step 5

Sildenafil DRUG

Parallel treatment with Sildenafil 20 mg 3-times per day is permitted if patient has been on a stable dose for 2 weeks prior to screening.

Treatment Step 2; Treatment step 1; Treatment step 3; Treatment step 4; Treatment step 5

TOP-N53 vehicle DRUG

TOP-N53 vehicle solution will be topically applied to digital ulcers of systemic sclerosis patients.

Treatment step 1

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who are able to understand and follow instructions during the clinical trial.
• Signed written informed consent in accordance with ICH-GCP and local legislation prior to admission to the clinical trial.
• Male or female participants aged 18 to 69 years\* at screening (V0) with SSc, limited or diffuse cutaneous, according to 2013 American College of Rheumatology (ACR)/EULAR criteria (\*sex refers to biological characteristics).
• At least one active DU, considered as the cardinal DU, due to SSc, ≥3 mm in diameter at screening (V0) and baseline (V1/V1b) with at least an involvement of the dermis, located at the fingertip.
• Participants meeting one of the following 2 criteria:
• On stable PO sildenafil treatment at 20 mg TID \[3 times per day\] for at least 2 weeks prior screening (V0).
• 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).
• 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 \[V1/V1b\]).
• 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.
• 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.
• 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).
• Covered by health insurance system and/or in compliance with the recommendations of national law in force relating to biomedical research.

You may not qualify if:

• Any DU accompanied by one of the following complications: Clinical infection of active ulcer/peri-ulcer, osteitis, gangrene (screening \[V0\] and baseline \[V1/V1b\]).
• Participants with modified Rodnan Skin Score (mRSS) \>35 (screening \[V0\]).
• Intractable pain from DUs (NRS ≥6) (screening \[V0\] and baseline \[V1/V1b\]).
• Active or previous history of calcinosis at the site of the designated cardinal DU.
• 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.
• 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.
• Participants with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment).
• 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 \<12 months.
• Systolic BP (SBP) \<95 mmHg or diastolic BP (DBP) \<50 mmHg , pulse rate \<50 beats per minute at sitting position (if participant is very athletic as assessed by the investigator, exception to a pulse \<50 bpm is permissible) at the screening visit (V0) or baseline visit (V1/V1b); one repeat measurement will be permitted.
• Clinically significant findings in the ECG at the screening visit (V0) or in historic ECG including 24 h Holter recordings, in particular prolongation of the QT interval corrected for HR (QTcB) ≥450 msec for men and ≥460 msec for women, ventricular arrhythmias or ectopic ventricular beats.
• Major surgery within 8 weeks prior to the screening visit (V0).
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 x upper limit of normal (ULN) and total Bilirubin \>1.5 x ULN.
• Estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula) formula ≤60 ml/min/1.73 m2 (corresponds to ≥ mildly to moderately reduced glomerular filtration rate \[GFR\]).
• Clinical laboratory values outside the reference range that in the investigator's opinion require further investigation and preclude enrollment into the clinical trial (clinically significant).
• Positive test for human immunodeficiency virus (HIV) antibodies, unless known from medical history.

Sponsors & Collaborators

• Topadur Pharma AG: lead
• Bioskin GmbH: collaborator

Study Sites (5)

Centre Hospitalier Universitaire de Bordeaux, Service de Rhumatologie

Bordeaux, 33000, France

RECRUITING

CHU Grenoble Alpes

La Tronche, 38 700, France

RECRUITING

CHRU Lille, Hôpital Claude Huriez, Rue Michel Polonosvski

Lille, 59000, France

RECRUITING

AP-HP Hôpital Cochin

Paris, 75014, France

RECRUITING

Reha Rheinfelden, Salinenstrasse 98

Rheinfelden, Canton of Aargau, 4310, Switzerland

RECRUITING

MeSH Terms

Conditions

digital ulcers; Scleroderma, Systemic

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Claudia Berger, Ph.D.

CONTACT

+41792025755; claudia.berger@Topadur.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The treatment will be performed sequentially with ascending doses and treatment durations of the IMP starting with placebo treatment. The next higher dose will only be applied after safety evaluation of data of at least 2 participants per treatment group.

Study Record Dates

• First Submitted: April 14, 2025
• First Posted: May 1, 2025
• Study Start: February 4, 2025
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: January 9, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); CH (1)