Dapagliflozin for Systemic sclerosis|Diffuse cutaneous systemic sclerosis (dcSSc)

Inclusion criteria

• {"criterion_text":"- Age > 18 years at the screening visit (W1).\n- Diagnosis of Systemic Sclerosis according to the 2023 ACR/EULAR criteria, confirmed by clinician.\n- Form of the disease: diffuse cutaneous systemic sclerosis (dcSSc), with involvement of the skin proximal to the metacarpophalangeal joints and/or the trunk.\n- Disease duration: ≤ 5 years from the first non-Raynaud’s symptom (the aim is to include patients in the early or intermediate fibrotic phase, when modification of the disease course is still possible).\n- Active skin fibrosis, defined as a Modified Rodnan Skin Score (mRSS) of 15–40 points at the screening visit (a range of 15–40 corresponds to the active fibrotic phase, in which the likelihood of reversibility of fibrosis-related changes is the highest).\n- Stable systemic sclerosis pharmacotherapy (if applicable) for ≥4 weeks prior to inclusion in the clinical trial (e.g., mycophenolate mofetil, methotrexate, phosphodiesterase-5 inhibitors).\n- Informed consent to participate in the study.\n- In laboratory tests performed during the screening period: - Absolute neutrophil count (ANC) ≥ 2 × 10⁹/L; - Platelet count ≥ 100 × 10³/μL; - Hemoglobin ≥ 8.0 g/dL; - Negative laboratory test results for QuantiFERON, HBsAg, anti-HIV, and anti-HCV.\n- Consent to use effective contraception by women of childbearing potential and men and their partners of reproductive potential during the time period of taking the investigational medicinal products and for at least 3 months after the last dose of the investigational medicinal product."}

Exclusion criteria

• {"criterion_text":"- Absolute contraindications to the use of any of the investigational medicinal product.\n- Known hypersensitivity to any ingredient of the investigational medicinal product.\n- Clinically significant, uncontrolled respiratory disease.\n- History of intestinal ulcers or diverticulitis, unless in the investigator’s opinion the patient’s current condition allows inclusion in the study.\n- Hepatic disfunction associated with out of range laboratory results: ALT ≥ 2x ULN and/or AST ≥ 2 x ULN, and/or total bilirubin ≥ 1,5 ULN.\n- Renal impairment (eGFR < 30 ml/min/1.73 m²) or ongoing use of renal replacement therapy, i.e., haemodialysis or peritoneal dialysis.\n- Heart failure class III or IV according to the New York Heart Association (NYHA) classification.\n- History of myocardial infarction or stroke within 6 months before investigational medicinal product administration.\n- Systolic blood pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg at the screening visit (Week 1).\n- Clinically significant uncontrolled diabetes, i.e., a condition in which diabetes was diagnosed prior to the screening visit and the most recent HbA1c result (not older than 6 months) is greater than 10%.\n- Active malignancy or history of malignancy within < 5 years before investigational medicinal product administration.\n- Any concomitant disease requiring surgery within < 7 days before investigational medicinal product administration.\n- Any other concomitant or prior disease that, in the investigator’s opinion, constitutes a contraindication to the patient’s participation in the clinical trial.\n- Inability or willingness to comply with the study protocol requirements or reasonable suspicion that the participant will not comply with the study protocol recommendations.\n- Confirmed history of alcohol or substance abuse, either currently or within 12 months prior to administration of the investigational medicinal product. Alcohol abuse is defined as more than 14 units of alcohol per week.\n- Participation in another clinical trial or research experiment within 4 weeks prior to the screening visit or within less than 5 half-lives of the investigational medicinal product, depending on which of these periods is longer.\n- Pregnancy or lactation.\n- Individuals lacking legal capacity.\n- Individuals lacking the capacity to independently provide informed consent for participation in the study.\n- Other medical condition that, in the investigator's opinion, could expose the patient to an increased risk of health deterioration during participation in the study.\n- A patient condition that prevents performing diagnostic tests such as HRCT, MRI, ECHO, and/or ECG, e.g., the presence of certain types of implants, contraindications to contrast agents, claustrophobia, or other conditions that contraindicate the examination."}

Primary endpoints

• {"endpoint_text":"- Change in disease severity in both arms assessed using the modified Rodnan Scale (mRSS) after 12 months of therapy. Non-inferiority assumption: the difference in improvement (reduction) between the study arms does not exceed 3 points.","definition_or_measurement_approach":"Measured by change in Modified Rodnan Skin Score (mRSS) at 12 months; non-inferiority margin defined as difference in improvement not exceeding 3 points between arms."}

Secondary endpoints

• {"endpoint_text":"- Change in the systemic sclerosis severity score for dapagliflozin compared to tocilizumab after 12 months of therapy. Superiority assumption: the difference in improvement (reduction) between the study arms exceeds 3 points in favor of dapagliflozin.","definition_or_measurement_approach":"Change in a systemic sclerosis severity score at 12 months; superiority threshold defined as >3-point greater improvement for dapagliflozin."}
• {"endpoint_text":"- Results of capillaroscopic examination according to the Cutolo scale after 12 months of therapy.","definition_or_measurement_approach":"Capillaroscopic assessment scored by the Cutolo scale at 12 months."}
• {"endpoint_text":"- Results of cardiac functional and morphological parameters assessed by magnetic resonance imaging (MRI) and echocardiography after 12 months of therapy.","definition_or_measurement_approach":"Cardiac function and morphology measured by MRI and echocardiography at 12 months."}
• {"endpoint_text":"- Results of morphological parameters of lung aeration on high-resolution computed tomography (HRCT) of the chest after 12 months of therapy.","definition_or_measurement_approach":"Lung aeration morphology assessed by HRCT at 12 months."}
• {"endpoint_text":"- Results of renal function parameters (eGFR, albuminuria) after 12 months of therapy.","definition_or_measurement_approach":"Renal function measured by eGFR and albuminuria at 12 months."}
• {"endpoint_text":"- Results of proinflammatory cytokine concentrations after 12 months of therapy.","definition_or_measurement_approach":"Measurement of proinflammatory cytokine concentrations at 12 months (method not specified in summary)."}
• {"endpoint_text":"- Results of a questionnaire developed by prof. Wioletta Tuszyńska-Bogucka, PhD, and standardized tools: the SF-36 Questionnaire, Pol-SScQoL Questionnaire (a scale designed to assess the quality of life of SSc patients), the Stress Assessment Questionnaire (KOS) by Wrześniewski et al., the Goldberg General Health Questionnaire (GHQ) in the Polish adaptation by Makowska and Merecz, the PHQ-9 Depression Scale, and the GAD-7 (Generalized Anxiety Disorder 7-item Scale) after 12 months of therapy.","definition_or_measurement_approach":"Patient-reported outcomes collected using listed questionnaires (SF-36, Pol-SScQoL, KOS, GHQ, PHQ-9, GAD-7 and a study-specific questionnaire) at 12 months."}
• {"endpoint_text":"- Safety assessment of the therapies used will include an analysis of the occurrence and characteristics of adverse events and serious adverse events during the study.","definition_or_measurement_approach":"Safety assessed by recording and analysing adverse events (AEs) and serious adverse events (SAEs) occurring during the study period."}

Poland

Earliest CTIS Part Ii Submission Date

28-11-2025

Latest Decision Or Authorization Date

15-12-2025

Processing Time Days

17

Number Of Sites

1

Number Of Participants

80

Primary sponsor

Full Name

Centrum Medyczne Ksztalcenia Podyplomowego

Organisation Type

Educational Institution

Country Of Registered Address

Poland

Third parties

• {"country":"","full_name":"Agencja Badań Medycznych","duties_or_roles":"Source of monetary support","organisation_type":""}