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Safety and tolerability of TOP-N53 applied on digital ulcers in patients with systemic sclerosis
EU CTIS ID: 2024-511861-12-00
What this study is testing
Clinical assessment of local safety and tolerability of the investigational product (IP) TOP N53/Vehicle, administered on wound by the topical route of administration on (active, ischemic) DUs located at fingertips, in SSc, at escalating dose levels (0 µg [Vehicle], 2 µg, 4 µg, 8 µg TOP-N53 in a hydrogel formulation, per wound) over 3 h exposure time (any dose) and 24 h exposure time (8 µg TOP-N53)
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Participants who are able to understand and follow instructions during the clinical trial
- Covered by health insurance system and/or in compliance with the recommendations of national law in force relating to biomedical research
- 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 at screening (V0) with SSc, limited or diffuse cutaneous, according to 2013 American College of Rheumatology (ACR)/EULAR criteria
- 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 fingertip or ischemic DU distal to the metacarpophalangeal joint
- Participants meeting one of the following 2 criteria: a. On stable PO sildenafil treatment at 20 mg TID [3 times per day] for at least 2 weeks prior screening (V0) or b. 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)
You likely can't join 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])
- 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
- 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
- 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)
See the full eligibility criteria
Who can join
- Participants who are able to understand and follow instructions during the clinical trial
- Covered by health insurance system and/or in compliance with the recommendations of national law in force relating to biomedical research
- 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 at screening (V0) with SSc, limited or diffuse cutaneous, according to 2013 American College of Rheumatology (ACR)/EULAR criteria
- 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 fingertip or ischemic DU distal to the metacarpophalangeal joint
- Participants meeting one of the following 2 criteria: a. On stable PO sildenafil treatment at 20 mg TID [3 times per day] for at least 2 weeks prior screening (V0) or b. 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 sterile1 or agree to use a highly effective birth control method (failure rate ˂1% per year when used consistently and correctly)2 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)
What rules you out
- Any DU accompanied by one of the following complications: Clinical infection of active ulcer/peri-ulcer, osteitis, gangrene (screening [V0] and baseline [V1/V1b])
- 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
- 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
- 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
- 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
- Participants with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment)
- In the opinion of the investigator the participant should not participate in the clinical trial if they are not expected to comply with the CTP 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
- 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)
- Participant is institutionalized because of legal or regulatory order
- Participants with modified Rodnan Skin Score (mRSS) >35 (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
- 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 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
- Participant is vulnerable (under legal protection)
- 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
- 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
- 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: a. Hypersensitivity to the active substance or to any of the excipients listed in Table 6 of the protocol. b. 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. c. 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. d. Combination with the most potent of the CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir). e. 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. f. 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
The study team makes the final eligibility decision.
Where it's taking place
- Switzerland
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Switzerland. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.