clinical trial evaluating the efficacy of nintedanib with tocilizumab compared to standard treatment in patients with systemic sclerosis and interstitial lung disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

1 Jul 2025 → 23 Mar 2026

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Agencja Badań Medycznych

External identifiers

EU CT number

2024-517005-85-00

EudraCT number

2022-003856-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

Evaluation of the efficacy and safety of nintedanib plus tocilizumab combination therapy compared to standard therapy (methotrexate, mycophenolate mofetil) over 56 weeks in patients with systemic sclerosis (TU) and interstitial lung disease (TU-ILD) defined as ≥10% lung involvement in assessed by high-resolution computed tomography (HRCT).

Secondary objectives 1

1. modification of the diagnostic path by PET examination, transcriptome, genome and metabolome tests and analysis of fibrosis markers in the lung tissue (bronchoscopy material, BAL) and serum - TGF-β, VEGF, IFN- γ, Kł-6, SP-D, CCL -2, CCL-18, CA15-3, CXCL-1, Ang1, Ang2 - included in the immune panel.

Conditions and MedDRA coding

systemic sclerosis with interstitial lung disease (ILD) in the course of the disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Men or women aged 18-74 at the date of signing the informed consent.
2. Written informed consent in accordance with the International Harmonization Guidelines Harmonized Tripartite Guidelines for Good Clinical Practice (ICH-GCP) and local regulations signed prior to any study procedure.
3. Documented diagnosis of systemic sclerosis according to the criteria of the American College of Rheumatology (ACR) and The European Alliance of Associations for Rheumatology (former name - European League Against Rheumatism) - EULAR, meeting the criteria of an active disease [patients with limited and generalized TUu)] and with an overall disease duration of less than or equal to (≤ 72 months)..
4. Patients with interstitial lung disease (ILD) confirmed by HRCT (min. 10% lung involvement).
5. Evaluation of skin induration with the modified Rodnan scale (mRSS) from 10 to 45 units inclusive.
6. Patients treated with conventional drugs such as mycophenolate mofetil, methotrexate; should be on stable doses for ≥ 8 weeks prior to and including the baseline visit (W0).
7. Patients may be treated with standard therapy, but no new therapy or withdrawal of therapy within 8 weeks prior to the first screening visit (W0).
8. Patients taking oral corticosteroids (GCS) should be on a stable dose of ≤ 10 mg/day prednisone or equivalent for at least 8 weeks prior to the baseline visit.
9. Patients of childbearing potential should agree to abstain from sexual activity or use a highly effective method of contraception throughout the study and for at least 3 months after the last dose of medicinal products.

Exclusion criteria 27

1. Patients not fully capable of giving informed consent.
2. Pregnant or breastfeeding women.
3. Major surgery within 8 weeks prior to screening (W0A).
4. Rheumatic disease other than systemic sclerosis (systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease), diagnosis of secondary Sjögren's syndrome is acceptable.
5. Active diverticulitis and severe enteritis.
6. Untreated lipid disorders (initiation of treatment and modification of the lipid profile enables re-screening for examination, rescreaning, after 8 weeks from the start of hypolipidemic treatment).
7. Immunization with a live or attenuated vaccine within 4 weeks prior to scheduled treatment.
8. Known hypersensitivity to human, humanized or murine monoclonal antibodies and hypersensitivity to peanut, soya.
9. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) >1.5 x ULN, if normalized, patient may be considered for re-screening.
10. Bilirubin >1.5 x ULN.
11. Creatinine clearance <30 ml/min.
12. Significant pulmonary hypertension (PH).
13. Airway obstruction (forced expiratory volume before bronchodilation in 1 second (FEV1)/FVC <0.7) and other clinically significant pulmonary abnormalities.
14. Cardiovascular diseases with heart failure NYHA III/IV.
15. More than 4 digital ulcers or a history of severe digital necrosis requiring hospitalization or severe other digital ulcers.
16. Bleeding risk (such as bleeding tendency, fibrinolysis, full dose of anticoagulants, high dose of antiplatelet therapy, history of central nervous system (CNS) bleeding events in the last year. (INR) >2, prothrombin time (PT) and partial thromboplastin (PTT) > 1.5 x ULN) and history of a thrombotic event within the last year, history of thrombosis still requiring full therapeutic anticoagulant therapy, fibrinolysis or high-dose antiplatelet therapy > 150 mg ASA per day.
17. History of stroke, myocardial infarction within 6 months prior to screening.
18. Prior treatment with pirfenidone and nintedanib if a minimum of 6 months had not been completed prior to enrolling the patient in the NINTOC-TU study.
19. Plasmapheresis and/or plasma exchange within the last 12 weeks prior to screening and use of immunoglobulins within the last 12 weeks and treatment with tocilizumab, treatments targeting B cell depletion, biologics (e.g. tumor necrosis factor antagonists), tyrosine kinase inhibitors, current treatment with alkylating agents (chlorambucil), autologous bone marrow transplantation, thalidomide, antithymocyte globulin, extracorporeal photopheresis.
20. Treatment with prednisone >10 mg/day, azathioprine, hydroxychloroquine, colchicine, D-penicillamine, sulfasalazine if within 8 weeks prior to W0. Cyclophosphamide within < 8 weeks of randomization visit (W 1). Rituximab within 6 months of visit (randomization W1).
21. Unstable (fluctuating) background therapy with mycophenolate mofetil or methotrexate in the last 8 weeks.
22. Patients with chronic liver disease (Child Pugh A, B, C hepatic impairment).
23. Active or significant history of infection, including treatment with intravenous antibiotics within the last 4 weeks or oral antibiotics within 2 weeks prior to screening. Including active confirmed tuberculosis or latent tuberculosis without chemoprophylaxis in accordance with applicable local recommendations. Active infection with HBV, HCV, Herpes-Zoster virus in the last 12 months. Human Immunodeficiency Virus (HIV) infection.
24. A positive result of the SARS-CoV-2 PCR test during the "0" visit is an exclusion criterion, while a history of infection more than 4 weeks before the screening tests and confirmed by a negative SARS-CoV-2 PCR test is not an exclusion criterion.
25. Active or history of malignancy, except for excised/cured local basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ.
26. Active or past drug or alcohol abuse.
27. The inability to understand and comply with the requirements of the protocol (lack of compliance) excludes from participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Decrease in forced vital capacity of the lungs FVC expressed in ml calculated after 56 weeks of treatment.

Secondary endpoints 10

1. Change from baseline in percent lung involvement as assessed by computed tomography (HRCT%) after 56 weeks of study.
2. Evaluation of absolute changes in DLCO at week 56 from baseline.
3. Evaluation of absolute changes from baseline in FVC% at 56 weeks.
4. Change from baseline in the 6MWT test at week 56.
5. Change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score at week 56.
6. Change in Patient's Global Assessment - PtGA (Physician's Global Assessment - PtGA) of disease activity by the patient and physician at week 56.
7. Evaluation of absolute changes from baseline in the total score of the St. George's Respiratory Questionnaire (SGRQ) at 56 weeks.
8. Evaluation of absolute changes from baseline in Modified Rodnan Skin Induration Score (mRSS) at Week 56.
9. Percentage of participants with threshold mRSS improvement from baseline at Week 56.
10. Percentage of participants with mRSS improvement greater than or equal to (> / =) 20%, 40% or 60% [time frame: baseline visit to week 56].

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher

Sponsor organisation

Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher

Address

Ul. Spartanska 1

City

Warsaw

Postcode

02-637

Country

Poland

Scientific contact point

Organisation

Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher

Contact name

Centrum Wsparcia Badań Klinicznych

Public contact point

Organisation

Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher

Contact name

Centrum Wsparcia Badań Klinicznych

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 6 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