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Digital Ulcers in Systemic SclerosisPhase 2TOP-N53-02NCT06954597

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

A Phase 2 study testing TOP-N53 and Sildenafil in people with Digital Ulcers in Systemic Sclerosis, run by Topadur Pharma AG at 6 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Digital Ulcers in Systemic Sclerosis
What is being tested?
TOP-N53 and Sildenafil
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
15 participants
Where
6 sitesin 2 countries
Study dates
4 Feb 2025to 31 Oct 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 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).
  • 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.
  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Positive hepatitis B-virus surface antigen (HBsAg) test, unless known from medical history.
  • Positive anti-hepatitis C-virus antibodies (anti-HCV) test, unless known from medical history.
  • Treatment with IV prostanoids: Either ongoing, or taken in the 4 weeks before enrollment or intended for the 4 weeks after last treatment with IP during the clinical trial.
  • Treatments with PO prostanoids (selexipag), nitrovasodilators (e.g., glycerol trinitrate, isosorbide dinitrate, isosorbide mononitrate, molsidomine), soluble guanylate cyclase stimulators (riociguat) for 1 week prior screening (V0).
  • Treatment with any other PDE5 inhibitor (tadalafil, vardenafil) except sildenafil if meeting inclusion criterion no. 5a or unselective PDE inhibitor (theophylline, dipyridamole) at any posology for the 4 weeks prior screening (V0) and during the clinical trial.
  • Treatment with systemic glucocorticoids and immunosuppressants (unless used as stable background treatments for SSc at unchanged doses [as prescribed by participant's treating physicians] for at least 4 weeks prior to screening [V0]).
  • Contraindications according to the IB of sildenafil and SmPC of Sildenafil-Teva only applicable for those participants meeting inclusion criterion no 5a:
  • Hypersensitivity to the active substance or to any of the excipients of sildenafil.
  • Co-administration with NO donors (such as amyl nitrite) or nitrates in any form due to the hypotensive effects of nitrates.
  • However, in the current clinical trial with the topical, on wound administration of the NO donor and PDE5 inhibitor TOP-N53 as IP 2 in patients on sildenafil any risk of hypotensive effects are minimal because the plasma exposure of TOP-N53 is expected as < MABEL.
  • The co-administration of PDE5 inhibitors, including sildenafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension.
  • Combination with the most potent of the CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir).
  • Participants who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure.
  • Recent history of stroke or myocardial infarction.
  • Known or suspected hypersensitivities or known allergic reactions to components of the IPs or other dressings required for SoC during the clinical trial treatment.
  • Known allergy to local amide anesthetics.
  • Currently enrolled in another clinical investigation or clinical trial, or less than 30 days prior to screening visit (V0) (less than 2 months for any investigative clinical trials with PDE5 inhibitors, guanylate cyclase activators or stimulators, or any other intervention interfering with the broader cGMP pathway) since ending another clinical investigation or clinical trial(s), or receiving other investigational treatment(s).
  • Pregnant women or breast-feeding women.
  • In the opinion of the investigator the participant should not participate in the clinical trial if they are not expected to comply with the clinical trial protocol requirements or not expected to complete the clinical trial as scheduled.
  • Close affiliation with the investigator (e.g., a close relative) or persons working at the clinical trial center(s) or participant is an employee of sponsor(s).
  • Participant is institutionalized because of legal or regulatory order.
  • Participant is vulnerable (under legal protection).

Trial locations and contacts

6 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Claudia Berger, Ph.D. contact

+41792025755

claudia.berger@Topadur.com

6 sites in 2 countries

France4 sites, 4 recruiting
  • Centre Hospitalier Universitaire de Bordeaux, Service de Rhumatologie

    Bordeaux, 33000

    Marie-Elise Truchetet, Professeur, +33.05.56.79.61.40, marie-elise.truchetet@chu-bordeaux.fr

    Justine Landrin, +33.05.56.79.61.40, justine.landrin@chu-bordeaux.fr

    Recruiting
  • CHU Grenoble Alpes

    La Tronche, 38 700

    Zaza Putkaradze, +33(0) 4 76 76 78 42, zputkaradze@chu-grenoble.fr

    Sophie Blaise, Professor

    Recruiting
  • CHRU Lille, Hôpital Claude Huriez, Rue Michel Polonosvski

    Lille, 59000

    Quentin Ducrocq, quentin.ducrocq@chu-lille.fr

    David Launay, Prof

    Recruiting
  • Hôpital Cochin

    Paris, 75014

    Ouardia Berkouk, +33 (0)1 58 41 15 03, ouardia.berkouk@aphp.fr

    Benjamin Chaigne, Dr

    Recruiting

Other trials in France

Switzerland2 sites, 2 recruiting
  • Reha Rheinfelden, Salinenstrasse 98

    Rheinfelden, Canton of Aargau, 4310

    Corina Schuster, Dr, c.schuster@reha-rhf.ch

    Ulrich Gerth, Dr

    Recruiting
  • Universitätsspital Zürich, Klinik für Rheumatologie, Rämistrasse 100

    Zurich, Canton of Zurich, 8091

    Eva-Maria Deschauer, Dr, +41 44 255 30 58, eva-maria.deschauer@usz.ch

    Meier Chantal, Dr., +41 44 255 30 58, chantal.meier@usz.ch

    Recruiting

Other trials in Switzerland

About this study

Official title: Local and Systemic Safety and Tolerability of Ascending Doses of TOP-N53, a Nitric Oxide (NO)-Releasing Phosphodiesterase-5 (PDE5) Inhibitor, Administered Topically, on Wounds in Patients With Digital Ulcers (DU) in Systemic Sclerosis (SSc) in an Open-label, Vehicle-controlled, Phase 2a, Multi-center Clinical Trial

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:

Read more
  • 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.

Being tested
TOP-N53, Sildenafil, TOP-N53 vehicle
Keywords
digital ulcer, systemic sclerosis, safety, PDE5 inhibitor
Medical subject headings
digital ulcers, Scleroderma, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TOP-N53Drug

    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.

  • SildenafilDrug

    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.

  • TOP-N53 vehicleDrug

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

Study groups in NCT06954597
Study groupRoleWhat they receive
Treatment step 1Placebo comparatorTreatment with vehicle (= 0 µg TOP-N53), 3h exposure
Receives: Drug: Sildenafil; Drug: TOP-N53 vehicle
Treatment Step 2ExperimentalTreatment with 2 µg TOP-N53, 3h exposure
Receives: Drug: TOP-N53; Drug: Sildenafil
Treatment step 3ExperimentalTreatment with 4 µg TOP-N53, 3h exposure
Receives: Drug: TOP-N53; Drug: Sildenafil
Treatment step 4ExperimentalTreatment with 8 µg TOP-N53, 3h exposure
Receives: Drug: TOP-N53; Drug: Sildenafil
Treatment step 5ExperimentalTreatment with 8 µg TOP-N53, 24h exposure
Receives: Drug: TOP-N53; Drug: Sildenafil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Local treatment emergent adverse events (TEAEs)

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

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

  2. 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']).

    Measured: 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)
  1. Clinical digital ulcer (DU) assessment (CDUA) endpoint - erythema at the peri ulcer area of the cardinal DU

    Frequency and mean score of erythema at the peri ulcer area of the cardinal DU (by scoring using a 7-point Robinson scale; score 0: no reaction, score 6: worst reaction (bullous reaction or grade 3-5 reaction spreading beyounf the DU)

    Measured: 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.

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

    Frequency of bruising at the peri-ulcer area of the cardinal DU or beyond (as assessed by closed question: YES/NO)

    Measured: 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.

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

    Frequency of hemorrhage in the cardinal DU (as assessed by closed question: YES/NO)

    Measured: 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.

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

    Frequency of perilesional newly emerging, wound related edema at the cardinal DU (as assessed by closed question: YES/NO)

    Measured: 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.

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

    Frequency of clinical infection at the cardinal DU (as assessed by closed question: YES/NO)

    Measured: 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.

  6. Investigator-solicited digital ulcer (DU)-related patient reported outcome (DU-PRO) - Itching

    Mean score of itching (actual) at the cardinal DU as assessed by using a numeric rating scale (NRS; graduating intensity from 0 ['no itch'] to 10 ['worst imaginable itch']).

    Measured: 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.

  7. Further investigator-solicited digital ulcer (DU) patient reported outcome (DU-PRO)

    Number of Raynaud's phenomenon (RP) attacks since IP initiation (0-5 minutes time point) and number of RP attacks since IP removal (60 minutes time point). RP attacks are defined as episodes of reduced blood flow to the end of blood vessels usually in fingers and toes.

    Measured: Per dose/time escalation step at 0-5 minutes after inititation of treatment and 60 minutes after removal of the IP within a time frame of up to 25 hours after IP application durng the trial period of up to 37 days.

  8. Systemic TEAEs

    Frequency of clinically significant abnormal values for:

    • Vital signs: Mean systemic arterial blood pressure and mean pulse rate, aural body temperature (only at screening, the enrollment visit for sildenafil participants, prior IP exposure when participant arrives, and at the Follow-up visit),
    • 12 lead electrocardiogram (ECG): mean and mean changes in ECG values,
    • Safety laboratory (clinical chemistry, hematology, urinalysis, serology): mean and mean changes in laboratory values.

    Measured: From treatment initiation until Follow-up visit; up to 37 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2025
  2. Study start4 Feb 2025
  3. Primary completion31 Oct 2026 (estimated)
  4. Study completion31 Oct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06954597
Sponsor's protocol ID
TOP-N53-02
Other IDs
2024-511861-12-00
Acronym
TOP-N53-02
Status last verified
Sep 2026
First submitted
14 Apr 2025
Last updated
1 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Apart from commercially confidential information related to the IMP, data collected in the course of this clinical trial is sparse. Therefore, there is no intention to share data as no benefit for the patient community is expected by the Sponsor. This will be reconsidered if larger cohort studies are initiated in the course of the development program.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TOP-N53 and Sildenafil in people with Digital Ulcers in Systemic Sclerosis, run by Topadur Pharma AG at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in France, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Claudia Berger, Ph.D. (+41792025755, claudia.berger@Topadur.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Local treatment emergent adverse events (TEAEs) (time frame: From first treatment until Follow-up visit; up to 37 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.

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