Comparison of treatment efficacy in the patients with Systemic sclerOsis: dapagliFlozin vs. Tocilizumab – a randomized head to head study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centrum Medyczne Ksztalcenia Podyplomowego

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Decision date (initial)

2025-12-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Agencja Badań Medycznych

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Comparison of the efficacy of dapagliflozin and tocilizumab in the treatment of patients with systemic sclerosis after 12 months of therapy.

Secondary objectives 8

1. Evaluation of whether treatment with dapagliflozin is more effective than treatment with tocilizumab in patients with systemic sclerosis after 12 months of therapy.
2. Assessment of the impact of dapagliflozin compared to tocilizumab on image of vessels in capillaroscopic examination in patients with systemic sclerosis after 12 months of therapy.
3. Assessment of the impact of dapagliflozin compared to tocilizumab on cardiac functional and morphological parameters in patients with systemic sclerosis after 12 months of therapy.
4. Assessment of the impact of dapagliflozin compared to tocilizumab on lung aeration parameters in patients with systemic sclerosis after 12 months of therapy.
5. Assessment of the impact of dapagliflozin compared to tocilizumab on kidney function in patients with systemic sclerosis after 12 months of therapy.
6. Assessment of the impact of dapagliflozin compared to tocilizumab on levels of proinflammatory cytokines in patients with systemic sclerosis after 12 months of therapy.
7. Comparison of affection of the threatment on the quality of life of patients with systemic sclerosis after 12 months of therapy.
8. Assessment of the safety of therapies used during the study.

Conditions and MedDRA coding

Systemic Sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age > 18 years at the screening visit (W1).
2. Diagnosis of Systemic Sclerosis according to the 2023 ACR/EULAR criteria, confirmed by clinician.
3. Form of the disease: diffuse cutaneous systemic sclerosis (dcSSc), with involvement of the skin proximal to the metacarpophalangeal joints and/or the trunk.
4. 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).
5. 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).
6. Stable systemic sclerosis pharmacotherapy (if applicable) for ≥4 weeks prior to inclusion in the clinical trial (e.g., mycophenolate mofetil, methotrexate, phosphodiesterase-5 inhibitors).
7. Informed consent to participate in the study.
8. 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.
9. 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 21

1. Absolute contraindications to the use of any of the investigational medicinal product.
2. Known hypersensitivity to any ingredient of the investigational medicinal product.
3. Clinically significant, uncontrolled respiratory disease.
4. History of intestinal ulcers or diverticulitis, unless in the investigator’s opinion the patient’s current condition allows inclusion in the study.
5. 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.
6. Renal impairment (eGFR < 30 ml/min/1.73 m²) or ongoing use of renal replacement therapy, i.e., haemodialysis or peritoneal dialysis.
7. Heart failure class III or IV according to the New York Heart Association (NYHA) classification.
8. History of myocardial infarction or stroke within 6 months before investigational medicinal product administration.
9. Systolic blood pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg at the screening visit (Week 1).
10. 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%.
11. Active malignancy or history of malignancy within < 5 years before investigational medicinal product administration.
12. Any concomitant disease requiring surgery within < 7 days before investigational medicinal product administration.
13. Any other concomitant or prior disease that, in the investigator’s opinion, constitutes a contraindication to the patient’s participation in the clinical trial.
14. Inability or willingness to comply with the study protocol requirements or reasonable suspicion that the participant will not comply with the study protocol recommendations.
15. 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.
16. 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.
17. Pregnancy or lactation.
18. Individuals lacking legal capacity.
19. Individuals lacking the capacity to independently provide informed consent for participation in the study.
20. 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.
21. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 8

1. 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.
2. Results of capillaroscopic examination according to the Cutolo scale after 12 months of therapy.
3. Results of cardiac functional and morphological parameters assessed by magnetic resonance imaging (MRI) and echocardiography after 12 months of therapy.
4. Results of morphological parameters of lung aeration on high-resolution computed tomography (HRCT) of the chest after 12 months of therapy.
5. Results of renal function parameters (eGFR, albuminuria) after 12 months of therapy.
6. Results of proinflammatory cytokine concentrations after 12 months of therapy.
7. 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.
8. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centrum Medyczne Ksztalcenia Podyplomowego

Sponsor organisation

Centrum Medyczne Ksztalcenia Podyplomowego

Address

Ul. Ulica Marymoncka 99/103

City

Warsaw

Postcode

01-813

Country

Poland

Scientific contact point

Organisation

Centrum Medyczne Ksztalcenia Podyplomowego

Contact name

Dyrektor Centrum Medycznego Kształcenia Podyplomowego

Public contact point

Organisation

Centrum Medyczne Ksztalcenia Podyplomowego

Contact name

Dyrektor Centrum Medycznego Kształcenia Podyplomowego

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications