AzTrials
AzTrials

Systemic SclerosisPhase 3NINTOC-TUNCT06297096

Study of the Efficacy of Nintedanib+Tocilizumab in Patients With Systemic Sclerosis and Interstitial Lung Disease

A Phase 3 study testing Tocilizumab, Nintedanib and Standard therapy in people with Systemic Sclerosis and Interstitial Lung Disease, run by National Institute of Geriatrics, Rheumatology and Rehabilitation, Poland at 1 site in Poland.

Recruiting

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

Sites and contacts
Official record
Search all trials

Trial summary

The study includes adult patients with systemic sclerosis (SSc) with interstitial lung disease (ILD) to evaluate the efficacy and safety of nintedanib plus tocilizumab combination therapy compared to standard therapy (methotrexate, mycophenolate mofetil) for 56 weeks. Read more about this study

Who is it for?
Ages 18 to 74 years
Conditions the study is for
Systemic Sclerosis, Interstitial Lung Disease
What is being tested?
Tocilizumab, Nintedanib and Standard therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
86 participants
Where
1 sitePoland
Study dates
1 Jul 2025to 30 Mar 2028
Phase
Phase 3
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 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men or women aged 18-74 at the date of signing the informed consent.
  • Written informed consent in accordance with the International Harmonization Guidelines Harmonized Tripartite: Guidelines for Good Clinical Practice (ICH-GCP) and local regulations signed before any study procedure.
  • 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 active disease [patients with limited and diffused SSc)] and with an overall disease duration of less than or equal to (≤ 72 months).
  • Patients with interstitial lung disease (ILD) confirmed by HRCT (min. 10% lung involvement).
  • Evaluation of skin induration with the modified Rodnan skin score (mRSS) from 10 to 45 units inclusive.
  • Patients treated with conventional drugs such as mycophenolate mofetil, methotrexate; should be on stable doses for ≥ 8 weeks before and including the screening visit (W0).
Show all 9Show fewer
  • Patients may be treated with standard therapy, but no new therapy or withdrawal of therapy within 8 weeks before the first screening visit (W0).
  • Patients taking oral glucocorticosteroids (GCS) should be on a stable dose of ≤ 10 mg/day prednisone or equivalent for at least 8 weeks before the baseline visit.
  • 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.

Who cannot join

  • Patients not fully capable of giving informed consent.
  • Pregnant or breastfeeding women.
  • Major surgery within 8 weeks before screening (W0A).
  • Rheumatic disease other than systemic sclerosis (systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease). Diagnosis of secondary Sjögren's syndrome is acceptable.
  • Active diverticulitis and severe enteritis.
  • Untreated lipid disorders (Initiation of treatment and modification of the lipid profile enable re-screening for examination after 8 weeks from the start of hypolipidemic treatment).
Show all 27Show fewer
  • Immunization with a live or attenuated vaccine within 4 weeks before scheduled treatment.
  • Known hypersensitivity to human, humanized or murine monoclonal antibodies and hypersensitivity to peanut, soya.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels greater than 1.5 times the upper limit of normal (ULN). If normalized, the patient may be considered for re-screening.
  • Bilirubin >1.5 x ULN.
  • Creatinine clearance <30 ml/min.
  • Significant pulmonary hypertension (PH).
  • Airway obstruction (forced expiratory volume before bronchodilation in 1 second (FEV1)/FVC <0.7) and other clinically significant pulmonary abnormalities.
  • Cardiovascular diseases with heart failure NYHA III/IV.
  • More than 4 digital ulcers or a history of severe digital necrosis requiring hospitalization or severe other digital ulcers.
  • 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.
  • History of stroke, or myocardial infarction within 6 months before screening.
  • Prior treatment with pirfenidone or nintedanib if a minimum of 6 months had not been completed before enrolling the patient in the NINTOC-TU study.
  • Plasmapheresis and/or plasma exchange within the last 12 weeks before 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.
  • Treatment with prednisone >10 mg/day, azathioprine, hydroxychloroquine, colchicine, D-penicillamine, sulfasalazine if within 8 weeks before W0. Cyclophosphamide within < 8 weeks of randomization visit (W 1). Rituximab within 6 months of visit (randomization W1).
  • Unstable (fluctuating) background therapy with mycophenolate mofetil or methotrexate in the last 8 weeks.
  • Patients with chronic liver disease (Child-Pugh A, B, C hepatic impairment).
  • Active or significant history of infection, including treatment with intravenous antibiotics within the last 4 weeks or oral antibiotics within 2 weeks before screening. Including active confirmed tuberculosis or latent tuberculosis without chemoprophylaxis following applicable local recommendations. Active infection with HBV, HCV, Herpes-Zoster virus in the last 12 months. Human Immunodeficiency Virus (HIV) infection.
  • 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.
  • Active or history of malignancy, except for excised/cured local basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ.
  • Active or past drug or alcohol abuse.
  • The inability to understand and comply with the requirements of the protocol (lack of compliance) excludes from participation in the study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Maria Maślińska, PhD, MD contact

226880632 ext. +48

maria.maslinska@spartanska.pl

Poland1 site, 1 recruiting

  • Centrum Wsparcia Badań Klinicznych

    Warsaw, Masovian Voivodeship, 02-637

    Justyna Kwiatkowska-Golańska, 22 6880632 ext. +48, justyna.kwiatkowska-golanska@spartanska.pl

    Maria Maślińska, PhD, MD

    Recruiting

Other trials in Poland

About this study

Official title: Multicentre Clinical Trial Evaluating the Safety and Efficacy of the Combination of Nintedanib+Tocilizumab Compared to Standard Treatment in Patients With Systemic Sclerosis and Interstitial Lung Disease. Analysis With Theranostic Approach

The study includes adult patients with systemic sclerosis (SSc) with interstitial lung disease (ILD) to evaluate the efficacy and safety of nintedanib plus tocilizumab combination therapy compared to standard therapy (methotrexate, mycophenolate mofetil) for 56 weeks.

Read the detailed description

Full title of the trial:

A multicentre clinical trial evaluating the safety and efficacy of the combination of nintedanib and tocilizumab compared to standard treatment in patients with systemic sclerosis and interstitial lung disease. Analysis with theranostic approach and assessment of cytokine activity, markers of inflammation and pulmonary fibrosis using computed tomography, positron emission tomography, and metabolome and transcriptome studies in selected patients. NINTOC-TU study.

Being tested
Tocilizumab, Nintedanib, Standard therapy
Keywords
systemic sclerosis, ILD, tocilizumab, nintedanib, combination therapy
Medical subject headings
Scleroderma, Systemic, Lung Diseases, Interstitial

What participants receive

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

  • TocilizumabDrug

    Tocilizumab 162 mg s.c./week

  • NintedanibDrug

    Nintedanib - established doses of nintedanib for adults in the treatment of ILD, also SSc-ILD: 2 x 150 mg daily, in the event of e.g. increased liver enzyme levels, poorer treatment tolerance (e.g. diarrhea), the dose can be reduced to 2 x 100 mg

  • Standard therapyDrug

    Also called mycophenolate mofetil, methotrexate

    mycophenolate mofetil stable dose from 1000 - 3000 mg daily tablet 500 mg or 250 mg regardless of the preparation (Mycofit, CellCept, Mycophenolate mofetil, Myfenax) or methotrexate 10-25 mg/week orally or subcutaneously as above, regardless of the preparation

Study groups in NCT06297096
Study groupRoleWhat they receive
combined therapy Nintedanib + Tocilizumab with or without standard treatment + extended diagnosticsExperimentaltocilizumab pre-filled syringe 162 mg subcutaneously once a week nintedanib tablets 150 mg twice a day or 2 x 100 mg a day
Receives: Drug: Tocilizumab; Drug: Nintedanib; Drug: Standard therapy
standard treatment (reference group) + extended diagnosticsActive comparatormycophenolate mofetil stable dose from 1000 - 3000 mg daily tablet 500 mg or 250 mg regardless of the preparation (Mycofit, CellCept, Mycophenolate mofetil, Myfenax) or methotrexate 10-25 mg/week orally or subcutaneously as above, regardless of the preparation
Receives: Drug: Standard therapy

What is being measured

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

  1. The decrease in forced vital capacity (FVC) of the lungs

    The decrease in forced vital capacity (FVC) of the lungs expressed in ml calculated after 56 weeks of treatment

    Measured: 56 weeks

Secondary outcomes (11)

  1. Change in percent lung involvement

    Change in percent lung involvement assessed by computed tomography (HRCT%) from baseline to assessment in 56 weeks of study

    Measured: 56 weeks

  2. Assessment of absolute changes in DLCO

    Assessment of absolute changes in DLCO at week 56 compared to baseline (baseline)

    Measured: 56 weeks

  3. Assessment of the absolute changes in predicted FVC%

    Assessment of the the absolute changes in predicted FVC% at week 56 from baseline

    Measured: 56 weeks

  4. Change in the Six-minute walk test (6MWT) result

    Change in the Six-minute walk test (6MWT) result at week 56 compared to the baseline value

    Measured: 56 weeks

  5. Change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score

    Change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score at week 56 (from min. 0 to max.3). Scores of 0 to 1 are generally considered to represent mild to moderate difficulty, 1 to 2 moderate to severe disability, and 2 to 3 severe to very severe disability.

    Measured: 56 weeks

  6. A change in the patient's global assessment of disease activity

    A change in the patient's global assessment of disease activity (Patient's Global Assessment - PtGA), assessment at week 56 - PtGA scoring on Visual Analog Scale from optimal condition - 0 mm (min) to 100 mm (max) - the worse condition.

    Measured: 56 weeks

  7. A change in the physician's global assessment of disease activity

    A change in the physician's global assessment of disease activity (Physician's Global Assessment - PGA), assessment at week 56 - PGA scoring on Visual Analog Scale from optimal condition - 0 mm (min) to 100 mm (max) - the worse condition.

    Measured: 56 weeks

  8. Assessment of the absolute changes from baseline in total scores in St. George's Respiratory Questionnaire (SGRQ)

    Assessment of the absolute changes from baseline in total scores in St. George's Respiratory Questionnaire (SGRQ) at 56 weeks. St. George's Respiratory Questionnaire (SGRQ) ranges from 1 to 100, where 0 indicates best health and 100 indicates worst health.

    Measured: 56 weeks

  9. Assessment of absolute changes compared to baseline values on the modified Rodnan skin Score (mRSS)

    Assessment of absolute changes compared to baseline values on the modified Rodnan skin Score (mRSS) at week 56. mRSS is a semiquantitative score, ranging from 0 (normal) to 3 (severe), used to evaluate the skin thickness in 17 different cutaneous sites (for a total score from 0 (good) to 51 (the worst condition).

    Measured: 56 weeks

  10. Percentage of participants with threshold improvement from baseline in modified Rodnan skin Score (mRSS)

    Percentage of participants with threshold improvement from baseline in modified Rodnan skin Score (mRSS) at week 56. mRSS is a semiquantitative score, ranging from 0 (normal) to 3 (severe), used to evaluate the skin thickness in 17 different cutaneous sites (for a total score from 0 (good) to 51 (the worst condition).

    Measured: 56 weeks

  11. Percentage of participants with modified Rodnan skin Score (mRSS) improvement greater than or equal to (>/=) 20%, 40%, or 60%

    Percentage of participants with modified Rodnan skin Score (mRSS) improvement greater than or equal to (>/=) 20%, 40%, or 60% [time frame: baseline to week 56]. mRSS is a semiquantitative score, ranging from 0 (normal) to 3 (severe), used to evaluate the skin thickness in 17 different cutaneous sites (for a total score from 0 (good) to 51 (the worst condition).

    Measured: Time frame: from baseline to week 56

Timeline

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

  1. First posted6 Mar 2024
  2. Study start1 Jul 2025
  3. Primary completion30 Dec 2027 (estimated)
  4. Study completion30 Mar 2028 (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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
86 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06297096
Sponsor's protocol ID
NIGRIR_004NINTOC-TU
Acronym
NINTOC-TU
Status last verified
Jan 2026
First submitted
29 Feb 2024
Last updated
8 Apr 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Richeldi L, Cottin V, Flaherty KR, Kolb M, Inoue Y, Raghu G, Taniguchi H, Hansell DM, Nicholson AG, Le Maulf F, Stowasser S, Collard HR. Design of the INPULSIS trials: two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis. Respir Med. 2014 Jul;108(7):1023-30. doi: 10.1016/j.rmed.2014.04.011. Epub 2014 Apr 29.

    PubMed 24834811

  • Inoue Y, Suda T, Kitamura H, Okamoto M, Azuma A, Inase N, Kuwana M, Makino S, Nishioka Y, Ogura T, Takizawa A, Ugai H, Stowasser S, Schlenker-Herceg R, Takeuchi T. Efficacy and safety of nintedanib in Japanese patients with progressive fibrosing interstitial lung diseases: Subgroup analysis of the randomised, double-blind, placebo-controlled, phase 3 INBUILD trial. Respir Med. 2021 Oct;187:106574. doi: 10.1016/j.rmed.2021.106574. Epub 2021 Aug 12.

    PubMed 34564020

  • Cottin V, Richeldi L, Rosas I, Otaola M, Song JW, Tomassetti S, Wijsenbeek M, Schmitz M, Coeck C, Stowasser S, Schlenker-Herceg R, Kolb M; INBUILD Trial Investigators. Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases. Respir Res. 2021 Mar 16;22(1):84. doi: 10.1186/s12931-021-01668-1.

    PubMed 33726766

  • Shima Y, Kawaguchi Y, Kuwana M. Add-on tocilizumab versus conventional treatment for systemic sclerosis, and cytokine analysis to identify an endotype to tocilizumab therapy. Mod Rheumatol. 2019 Jan;29(1):134-139. doi: 10.1080/14397595.2018.1452178. Epub 2018 Apr 9.

    PubMed 29529897

  • Denton CP, De Lorenzis E, Roblin E, Goldman N, Alcacer-Pitarch B, Blamont E, Buch M, Carulli M, Cotton C, Del Galdo F, Derrett-Smith E, Douglas K, Farrington S, Fligelstone K, Gompels L, Griffiths B, Herrick A, Hughes M, Pain C, Pantano G, Pauling J, Prabu A, O'Donoghue N, Renzoni E, Royle J, Samaranayaka M, Spierings J, Tynan A, Warburton L, Ong V. Management of systemic sclerosis: British Society for Rheumatology guideline scope. Rheumatol Adv Pract. 2023 Mar 14;7(1):rkad022. doi: 10.1093/rap/rkad022. eCollection 2023.

    PubMed 36923262

  • Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allanore Y, Distler O, Clements P, Cutolo M, Czirjak L, Damjanov N, Del Galdo F, Denton CP, Distler JHW, Foeldvari I, Figelstone K, Frerix M, Furst DE, Guiducci S, Hunzelmann N, Khanna D, Matucci-Cerinic M, Herrick AL, van den Hoogen F, van Laar JM, Riemekasten G, Silver R, Smith V, Sulli A, Tarner I, Tyndall A, Welling J, Wigley F, Valentini G, Walker UA, Zulian F, Muller-Ladner U; EUSTAR Coauthors. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017 Aug;76(8):1327-1339. doi: 10.1136/annrheumdis-2016-209909. Epub 2016 Nov 9.

    PubMed 27941129

  • Khanna D, Lescoat A, Roofeh D, Bernstein EJ, Kazerooni EA, Roth MD, Martinez F, Flaherty KR, Denton CP. Systemic Sclerosis-Associated Interstitial Lung Disease: How to Incorporate Two Food and Drug Administration-Approved Therapies in Clinical Practice. Arthritis Rheumatol. 2022 Jan;74(1):13-27. doi: 10.1002/art.41933. Epub 2021 Nov 10.

    PubMed 34313399

  • Flaherty KR, Brown KK, Wells AU, Clerisme-Beaty E, Collard HR, Cottin V, Devaraj A, Inoue Y, Le Maulf F, Richeldi L, Schmidt H, Walsh S, Mezzanotte W, Schlenker-Herceg R. Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Respir Res. 2017 Sep 17;4(1):e000212. doi: 10.1136/bmjresp-2017-000212. eCollection 2017.

    PubMed 29018526

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tocilizumab, Nintedanib and Standard therapy in people with Systemic Sclerosis and Interstitial Lung Disease, run by National Institute of Geriatrics, Rheumatology and Rehabilitation, Poland at 1 site in Poland.

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 9 inclusion and 27 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 8 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Poland. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 Maria Maślińska, PhD, MD (226880632 ext. +48, maria.maslinska@spartanska.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The decrease in forced vital capacity (FVC) of the lungs (time frame: 56 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06297096, which also lists 8 linked publications.

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 8 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in