Safety and Efficacy of Itacitinib in Adults With Systemic Sclerosis

NCT04789850 | Recruiting Phase 2 DMC

• 2 other identifiers: APHP1806132019-003430-16
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 46

Brief Summary

The purpose of this study is to determine whether itacitinib is safe and effective in the treatment of systemic sclerosis in adults.

Conditions

Systemic Sclerosis

Keywords

Systemic sclerosis; Itacitinib

Outcome Measures

Primary Outcomes (1)

• Change in modified Rodnan skin score (mRSS) at 360 days

  performed by the same investigator at day 0 and day 360 and the change in mRSS will be calculated following the formula: ΔmRSS= mRSSd360 - mRSSd0. To measure mRSS, skin thickness of the patient is rated by palpation at each of 17 anatomic sites using a scale of 0-3 (0 = normal skin; 1= mild thickness; 2= moderate thickness; 3=severe thickness with an inability to pinch the skin into a fold). The scores at each site are summed with a minimum of 0 and a maximum of 51 (17 sites)

  360 days

Secondary Outcomes (11)

• Incidence of death

  at 180 and 360 days

• Incidence of Adverse Events

  at 180 and 360 days

• Incidence of Severe Adverse Events

  at 180 and 360 days

• Change in modified Rodnan skin score at 90, 180, 270 days

  at 90, 180 and 270 days

• Proportion of patients who improved mRSS at 90, 180, 270 and 360 days

  At 90, 180, 270 and 360 days

Study Arms (2)

Itacitinib

EXPERIMENTAL

200mg of oral Itacitinib everyday for 360 days.

Drug: Itacitinib

Placebo

PLACEBO COMPARATOR

Oral placebo everyday for 360 days.

Drug: Placebo

Interventions

Itacitinib DRUG

200 mg oral for 360 days

Itacitinib

Placebo DRUG

200 mg oral for 360 days

Placebo

Eligibility Criteria

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

You may qualify if:

• Adult patient (≥18 years old)
• Patient with a diagnosis of diffuse SSc, as defined by the American College of Rheumatology / EULAR 2013 criteria,
• Patient with a diffuse SSc, according to Leroy and Medsger dichotomy
• Patient with a SSc disease duration of less than 36 months (defined as time from first non-Raynaud phenomenon manifestation) or with an active SSc disease, as defined by EUSTAR disease activity score,
• Patient with a modified Rodnan skin score (mRSS) ≥ 10 and ≤ 35 units at screening,
• Negative pregnancy test for woman of childbearing potential, woman of childbearing potential should have reliable contraception for the 12 months' duration of the study,
• Patient able to give written informed consent prior to participation in the study,
• Affiliation to a social security scheme (profit or being entitled)
• If patients receive mycophenolate or methotrexate for SSc, these need to be on stable dose as follows:
• Mycophenolate mofetil/sodium: stable dose for at least 2 months prior to randomisation
• Methotrexate: stable dose and route of administration for at least 2 months prior to randomisation

You may not qualify if:

• Previous treatment with itacitinib or a Janus kinase (JAK) inhibitor,
• Contra-indications to itacitinib or Janus kinase inhibitor,
• Failure to sign the informed consent or unable to consent
• Patient participating in another investigational therapeutic study,
• Acute or chronic active infections, including HBV, HCV, HIV,
• Patient with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol,
• Patient suspected not to be observant to the proposed treatments,
• Patient who have white blood cell count ≤ 4,000/mm3,
• Patient who have platelet count ≤ 100,000/mm3,
• Patients who have ALT or AST level greater that 3 times the upper limit of normal,
• Patient who have triglyceride level greater than 5g/L
• Pregnant or breastfeeding woman,
• Protected adults (including individual under guardianship by court order),
• Patient with Systemic Lupus, or Sjögren's syndrome with systemic manifestations justifying immunosuppressive therapy
• Atherosclerotic cardiovascular disease as defined by a history of myocardial infarction, ischaemic stroke, or peripheral artery thrombosis

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (46)

CH Amiens

Amiens, 80000, France

RECRUITING

CHU Angers

Angers, 49100, France

RECRUITING

CHU Annecy

Annecy, 74370, France

RECRUITING

CHU Besançon

Besançon, 25030, France

RECRUITING

Avicenne Hospital

Bobigny, 93022, France

RECRUITING

CHU Bordeaux

Bordeaux, 33000, France

RECRUITING

CHU Bordeaux

Bordeaux, 33000, France

RECRUITING

Ambroise Paré hospital

Boulogne-Billancourt, 92100, France

RECRUITING

Hôpital de la Cavale Blanche

Brest, 29200, France

RECRUITING

CHU Caen

Caen, 14000, France

RECRUITING

CHU Gabriel Montpied

Clermont-Ferrand, 63000, France

RECRUITING

Henry Mondor hospital

Créteil, 94000, France

RECRUITING

CH Dax-Côte d'ARgent

Dax, 40100, France

RECRUITING

CHU Dijon

Dijon, 21000, France

RECRUITING

CHU Grenoble

Grenoble, 38700, France

RECRUITING

CHU Grenoble

Grenoble, 38700, France

RECRUITING

CH Le Mans

Le Mans, 72037, France

RECRUITING

CHU Lille

Lille, 59000, France

RECRUITING

CHU Limoges

Limoges, 87000, France

RECRUITING

CHU Lyon sud

Lyon, 69310, France

RECRUITING

Hôpital Nord

Marseille, 13015, France

RECRUITING

La Timone Hospital

Marseille, 13385, France

RECRUITING

La Timone Hospital

Marseille, 13385, France

RECRUITING

Robert Schuman Hospital

Metz, 57000, France

RECRUITING

CHU Montpellier - rhumatology

Montpellier, 34090, France

RECRUITING

CHU Montpellier - St Eloi Hospital

Montpellier, 34090, France

RECRUITING

CHU Nancy

Nancy, 54035, France

RECRUITING

CHU Nantes

Nantes, 44093, France

RECRUITING

Hopital L'Archet 1

Nice, 06000, France

RECRUITING

Hospital Pasteur - CHU Nice

Nice, 06000, France

RECRUITING

Saint Antoine Hospital

Paris, 75012, France

NOT YET RECRUITING

La Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

La Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

Cochin Hospital

Paris, 75014, France

RECRUITING

Hospital Croix St Simon

Paris, 75020, France

NOT YET RECRUITING

CHU Poitiers

Poitiers, 86021, France

RECRUITING

CH de Cornouaille

Quimper, 29000, France

RECRUITING

Robert Debré Hospital

Reims, 51100, France

RECRUITING

Hôpital Sud

Rennes, 35200, France

RECRUITING

CHU Rouen

Rouen, 76000, France

NOT YET RECRUITING

CHU Saint Etienne

Saint-Etienne, 42000, France

RECRUITING

Nouvel Hospital Civil

Strasbourg, 67000, France

RECRUITING

Rangueil Hospital

Toulouse, 31400, France

RECRUITING

CHU Tours

Tours, 37000, France

RECRUITING

CH Valenciennes

Valenciennes, 59300, France

RECRUITING

Hôpitaux de Barbois

Vandœuvre-lès-Nancy, 54500, France

RECRUITING

Related Publications (14)

• Almeida C, Almeida I, Vasconcelos C. Quality of life in systemic sclerosis. Autoimmun Rev. 2015 Dec;14(12):1087-96. doi: 10.1016/j.autrev.2015.07.012. Epub 2015 Jul 23.

  PMID: 26212726 BACKGROUND

• Mouthon L. SSc in 2011: From mechanisms to medicines. Nat Rev Rheumatol. 2012 Jan 10;8(2):72-4. doi: 10.1038/nrrheum.2011.203.

  PMID: 22231235 BACKGROUND

• Distler JH, Feghali-Bostwick C, Soare A, Asano Y, Distler O, Abraham DJ. Review: Frontiers of Antifibrotic Therapy in Systemic Sclerosis. Arthritis Rheumatol. 2017 Feb;69(2):257-267. doi: 10.1002/art.39865. No abstract available.

  PMID: 27636741 BACKGROUND

• Wang Y, Fan PS, Kahaleh B. Association between enhanced type I collagen expression and epigenetic repression of the FLI1 gene in scleroderma fibroblasts. Arthritis Rheum. 2006 Jul;54(7):2271-9. doi: 10.1002/art.21948.

  PMID: 16802366 BACKGROUND

• Landi C, Bargagli E, Bianchi L, Gagliardi A, Carleo A, Bennett D, Perari MG, Armini A, Prasse A, Rottoli P, Bini L. Towards a functional proteomics approach to the comprehension of idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis and pulmonary Langerhans cell histiocytosis. J Proteomics. 2013 May 27;83:60-75. doi: 10.1016/j.jprot.2013.03.006. Epub 2013 Mar 23.

  PMID: 23528693 BACKGROUND

• Kubo M, Ihn H, Yamane K, Tamaki K. Up-regulated expression of transforming growth factor beta receptors in dermal fibroblasts in skin sections from patients with localized scleroderma. Arthritis Rheum. 2001 Mar;44(3):731-4. doi: 10.1002/1529-0131(200103)44:33.0.CO;2-U. No abstract available.

  PMID: 11263790 BACKGROUND

• Zhang Y, Liang R, Chen CW, Mallano T, Dees C, Distler A, Reich A, Bergmann C, Ramming A, Gelse K, Mielenz D, Distler O, Schett G, Distler JHW. JAK1-dependent transphosphorylation of JAK2 limits the antifibrotic effects of selective JAK2 inhibitors on long-term treatment. Ann Rheum Dis. 2017 Aug;76(8):1467-1475. doi: 10.1136/annrheumdis-2016-210911. Epub 2017 May 6.

  PMID: 28478401 BACKGROUND

• Migita K, Izumi Y, Torigoshi T, Satomura K, Izumi M, Nishino Y, Jiuchi Y, Nakamura M, Kozuru H, Nonaka F, Eguchi K, Kawakami A, Motokawa S. Inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway in rheumatoid synovial fibroblasts using small molecule compounds. Clin Exp Immunol. 2013 Dec;174(3):356-63. doi: 10.1111/cei.12190.

  PMID: 23968543 BACKGROUND

• Xu Y, Wang W, Tian Y, Liu J, Yang R. Polymorphisms in STAT4 and IRF5 increase the risk of systemic sclerosis: a meta-analysis. Int J Dermatol. 2016 Apr;55(4):408-16. doi: 10.1111/ijd.12839. Epub 2015 Dec 29.

  PMID: 26712637 BACKGROUND

• Avouac J, Furnrohr BG, Tomcik M, Palumbo K, Zerr P, Horn A, Dees C, Akhmetshina A, Beyer C, Distler O, Schett G, Allanore Y, Distler JH. Inactivation of the transcription factor STAT-4 prevents inflammation-driven fibrosis in animal models of systemic sclerosis. Arthritis Rheum. 2011 Mar;63(3):800-9. doi: 10.1002/art.30171.

  PMID: 21360510 BACKGROUND

• Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D, Krishnaswami S, Burgos-Vargas R, Wilkinson B, Zerbini CA, Zwillich SH. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum. 2009 Jul;60(7):1895-905. doi: 10.1002/art.24567.

  PMID: 19565475 BACKGROUND

• Fridman JS, Scherle PA, Collins R, Burn T, Neilan CL, Hertel D, Contel N, Haley P, Thomas B, Shi J, Collier P, Rodgers JD, Shepard S, Metcalf B, Hollis G, Newton RC, Yeleswaram S, Friedman SM, Vaddi K. Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation. J Invest Dermatol. 2011 Sep;131(9):1838-44. doi: 10.1038/jid.2011.140. Epub 2011 Jun 16.

  PMID: 21677670 BACKGROUND

• Deverapalli SC, Rosmarin D. The use of JAK inhibitors in the treatment of progressive systemic sclerosis. J Eur Acad Dermatol Venereol. 2018 Aug;32(8):e328. doi: 10.1111/jdv.14876. Epub 2018 Mar 6. No abstract available.

  PMID: 29444362 BACKGROUND

• Gordon JK, Martyanov V, Franks JM, Bernstein EJ, Szymonifka J, Magro C, Wildman HF, Wood TA, Whitfield ML, Spiera RF. Belimumab for the Treatment of Early Diffuse Systemic Sclerosis: Results of a Randomized, Double-Blind, Placebo-Controlled, Pilot Trial. Arthritis Rheumatol. 2018 Feb;70(2):308-316. doi: 10.1002/art.40358. Epub 2017 Dec 29.

  PMID: 29073351 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

itacitinib

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Luc Mouthon, MD-PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

• Benjamin Chaigne, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Chaigne, MD

CONTACT

+33 1 58 41 41 17; benjamin.chaigne@aphp.fr

Adèle BELLINO

CONTACT

+33 1 58 41 11 95; adele.bellino@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2021
• First Posted: March 10, 2021
• Study Start: February 2, 2023
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: November 20, 2025

Record last verified: 2025-10

Locations

FR (46)