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

NCT06297096 | Recruiting Phase 3

• 1 other identifier: NIGRIR_004NINTOC-TU
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Systemic Sclerosis; Interstitial Lung Disease

Keywords

systemic sclerosis; ILD; tocilizumab; nintedanib; combination therapy

Outcome Measures

Primary Outcomes (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

  56 weeks

Secondary Outcomes (11)

• Change in percent lung involvement

  56 weeks

• Assessment of absolute changes in DLCO

  56 weeks

• Assessment of the absolute changes in predicted FVC%

  56 weeks

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

  56 weeks

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

  56 weeks

Study Arms (2)

combined therapy Nintedanib + Tocilizumab with or without standard treatment + extended diagnostics

EXPERIMENTAL

tocilizumab pre-filled syringe 162 mg subcutaneously once a week nintedanib tablets 150 mg twice a day or 2 x 100 mg a day

Drug: Tocilizumab; Drug: Nintedanib; Drug: Standard therapy

standard treatment (reference group) + extended diagnostics

ACTIVE COMPARATOR

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

Drug: Standard therapy

Interventions

Tocilizumab DRUG

Tocilizumab 162 mg s.c./week

combined therapy Nintedanib + Tocilizumab with or without standard treatment + extended diagnostics

Nintedanib DRUG

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

combined therapy Nintedanib + Tocilizumab with or without standard treatment + extended diagnostics

Standard therapy DRUG

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

Also known as: mycophenolate mofetil, methotrexate

combined therapy Nintedanib + Tocilizumab with or without standard treatment + extended diagnostics; standard treatment (reference group) + extended diagnostics

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• National Institute of Geriatrics, Rheumatology and Rehabilitation, Poland: lead
• Medical Research Agency, Poland: collaborator

Study Sites (1)

Centrum Wsparcia Badań Klinicznych

Warsaw, Masovian Voivodeship, 02-637, Poland

RECRUITING

Related Publications (8)

• 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.

  PMID: 24834811 BACKGROUND

• 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.

  PMID: 34564020 BACKGROUND

• 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.

  PMID: 33726766 BACKGROUND

• 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.

  PMID: 29529897 BACKGROUND

• 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.

  PMID: 36923262 BACKGROUND

• 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.

  PMID: 27941129 BACKGROUND

• 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.

  PMID: 34313399 BACKGROUND

• 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.

  PMID: 29018526 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic; Lung Diseases, Interstitial

Interventions

tocilizumab; nintedanib; Standard of Care; Mycophenolic Acid; Methotrexate

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Maria Maślińska, PhD, MD

  National Institute of Geriatrics,Rheumatology and Rehabilitation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Maślińska, PhD, MD

CONTACT

226880632; maria.maslinska@spartanska.pl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 6, 2024
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): March 30, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)