Baricitinib in the Treatment of New-onset Juvenile Dermatomyositis (MYOCIT)

Overview

The MYOCIT study aims to evaluate the efficacy and safety of baricitinib in association with corticosteroids in new-onset patients with juvenile dermatomyositis (JDM) in a phase II trial with the objective to obtain a better efficacy than the conventional combination methotrexate (MTX) and corticosteroids over the 24 week study period. Thus, the investigators hypothesize that baricitinib could be used as a first line treatment in all forms of DMJ, including the most severe one, with a good safety profile.

Full Title of Study: “Baricitinib in the Treatment of New-onset Juvenile Dermatomyositis”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 2026

Detailed Description

Juvenile dermatomyositis (JDM) is a rare and severe paediatric-onset idiopathic inflammatory myopathy, associated with significant morbidity and mortality. The combination of corticosteroids and methotrexate (MTX) is recommended in new-onset JDM according to one randomized trial. However, in this trial, treatment failures were reported in 13/46 (28%) patients and severe JDM, (cutaneous or gastrointestinal ulceration, interstitial pulmonary disease, cardiomyopathy) were not taken into account. These data emphasize the need for a more efficient first-line treatment. Considering: 1) the strong implication of type IFN-I in the pathophysiology of JDM 2) the report of the efficacy and safety of JAK inhibitors (JAKis) (baricitinb, tofacitinib) in about 50 refractory DM patients, and 9 JDM, a trial which evaluates the efficacy and safety of baricitinib in combination with corticosteroids in new-onset JDM is warranted.

Interventions

  • Drug: Baricitinib
    • Oral tablets (2 mg) will be used For children > or = 6 years: 4 mg once a day (2 x 2 mg) during the 24 weeks-period study For children < 6 years: 2 mg once a day during the 24 weeks -period study
  • Biological: pharmacokinetics study
    • additionnal blood sampling at week 4, 8, 12, and 24
  • Biological: dosage of cytokines
    • additionnal blood sampling at weeks 0, 4 and 24
  • Biological: transcriptomic analysis
    • additionnal blood sampling at weeks 0, 4 and 24
  • Behavioral: Parent version of the Child Health Questionnaire (CHQ)
    • Evaluate by parents at each visits
  • Behavioral: Childhood Health Assessment Questionnaire
    • Evaluate by parents at each visits
  • Biological: Pregnancy test
    • Urine pregnancy test at V4 A dosage of bHCG with current biological analysis is done at each visit (except V4)

Arms, Groups and Cohorts

  • Experimental: Baricitinib

Clinical Trial Outcome Measures

Primary Measures

  • PRINTO 20 (Paediatric Rheumatology INternational Trials Organisation scale)
    • Time Frame: At week 24
    • Achievement of the validated juvenile dermatomyositis PRINTO 20 level of improvement. PRINTO 20 level of improvement is defined as a 20% or greater improvement in three or more of the six variables of the juvenile dermatomyositis core set, with one or no variable worsening by more than 30% (muscle strength can not be the variable worsening) : muscle strength, assessed with the Childhood Myositis Assessment Scale (CMAS), physician’s global assessment of the patient’s disease activity (Physician’s VAS) global disease activity assessment through the Disease Activity Score (DAS) functional ability through the Childhood Health Assessment Questionnaire (C-HAQ) parent’s global assessment of the child’s overall wellbeing (Parent’s VAS) health-related quality of life, through the parent version of the Child Health Questionnaire (CHQ-Phs) A higher score is 100% and means a better outcome, a lower score is 0% and means a worse result.

Secondary Measures

  • PRINTO 20 Paediatric Rheumatology INternational Trials Organisation scale – level 20
    • Time Frame: At week 4, 8, 12 and 16
    • achievement of the validated juvenile dermatomyositis PRINTO 20 level ; reaching a minimum of 20 % a higher score is 100% and mean a better outcome a lower score is 0% and means a worse result
  • PRINTO 50 Paediatric Rheumatology INternational Trials Organisation scale – level 50
    • Time Frame: At week 4, 8, 12 and 16
    • achievement of the validated juvenile dermatomyositis PRINTO 50 level ; reaching a minimum of 50 % a higher score is 100% and mean a better outcome a lower score is 0% and means a worse result
  • PRINTO 70 Paediatric Rheumatology INternational Trials Organisation scale – level 70
    • Time Frame: At week 4, 8, 12 and 16
    • achievement of the validated juvenile dermatomyositis PRINTO 70 level ; reaching a minimum of 70 % a higher score is 100% and mean a better outcome a lower score is 0% and means a worse result
  • PRINTO 90 Paediatric Rheumatology INternational Trials Organisation scale – level 90
    • Time Frame: At week 4, 8, 12 and 16
    • achievement of the validated juvenile dermatomyositis PRINTO 90 level ; reaching a minimum of 90 % a higher score is 100% and mean a better outcome a lower score is 0% and means a worse result
  • Total Improvement Score (TIS)
    • Time Frame: At inclusion, weeks 4, 8, 12, 16 and 24
    • Relative and absolute variations of TIS. The TIS is the sum of the improvement in each of the six core set measures of disease activits The minimum score is 0 (worse) and maximum score is 100 (better) A major response is defined by a score > 70 A moderate response is defined by a score > 45 A minimal response is defined by a score > 30
  • Clinically inactive disease
    • Time Frame: At weeks 4, 8, 12 and 24
    • according to the PRINTO criteria
  • Cutaneous Dermatomyositis Disease Area and Severity Index (CDSAI)
    • Time Frame: At inclusion, weeks 4, 8, 12, 16 and 24
    • assess skin activity and damage across multiple body regions in patients with dermatomyositis
  • Myositis Disease Activity Assessment VAS (MYOACT)
    • Time Frame: At inclusion, weeks 4, 8, 12, 16 and 24
    • Assess Relative and absolute variations of extramuscular activity
  • interstitial lung disease
    • Time Frame: At inclusion and at week 24
    • Assessed by improvement of at least 10% of FCV, PTC, and DLCO and/or improvement of Lung tomodensitomery according to a specific scale
  • Dose of corticosteroid
    • Time Frame: At week 24
    • Dose tapering at 6 months
  • Pharmacokinetics study
    • Time Frame: At weeks 4, 8, 12, and 24
    • Non-compartmental analysis of baricitinib
  • Pharmacokinetics (PK) study with area under the curve
    • Time Frame: At weeks 4, 8, 12, and 24
    • Correlation between area under the curve AUC in ng.h/ml (PK parameter of baricitinib) and disease activity ‘s scores
  • Pharmacokinetics (PK) study with maximal concentration
    • Time Frame: At weeks 4, 8, 12, and 24
    • Correlation between maximal concentration Cmax in ng/mL (PK parameter of baricitinib) and disease activity ‘s scores
  • Pharmacokinetics (PK) study with through concentration
    • Time Frame: At weeks 4, 8, 12, and 24
    • Correlation between through concentration Ctrough, in ng/mL (PK parameter of baricitinib) and disease activity ‘s scores
  • dosage of cytokines
    • Time Frame: At inclusion, weeks 4 and 24
    • Measurement of serum IFN -, IFN-γ, IL-1β, IL-4, Il-5, IL-6, IL-8, IL-10, IL-12p70, IL-22, TNF α
  • transcriptomic analysis
    • Time Frame: At inclusion, weeks 4 and 24
    • Study of genes expression within 800 genes related to immunity
  • Biopsy
    • Time Frame: At inclusion, weeks 4 and 24
    • Assessment of muscle biopsies according to the internationally validated score system

Participating in This Clinical Trial

Inclusion Criteria

  • Patient aged 3-18 years with new-onset juvenile dermatomyositis, according to the ENMC 2018 dermatomyositis classification criteria – Muscle weakness at MMT and/or CMAS (MMT < 74 and/or CMAS < 45) – Seropositivity or vaccination for chickenpox – For patients of childbearing age (following menarche) : Negative βHCG and effective method of contraception (sexual abstinence, hormonal contraception, intrauterine device or hormone-releasing system, cap, diaphragm or sponge with spermicide, condom) until the 7 days after administration of the last dose of Baricitinib – Informed consent form signed by the patient or child' s parents Patient affiliated to a social security regime Exclusion Criteria – Amyopathic dermatomyositis (without muscle weakness) – Inability to be treated by oral way or to take pills – Previous treatment with JAK inhibitor – Previous treatment of JDM with immunosuppressive drugs or biologics other than corticosteroids. Previous treatment with prednisone was allowed for no more than 1 month. – Previous history of cancer – Live vaccine within the 4 weeks before starting baricitinib therapy – Current, or recent (< 4 weeks prior to baseline) of active infections according to investigator appreciation, but necessarily, including HBV, HCV, HIV, tuberculosis. – Positive blood CMV PCR – Creatinine clearance < 40 ml/min – Lymphocytes < 0,5×109 cell/L and Neutrophils < 1×109 cell/L – Hemoglobin < 8 g/dL – Symptomatic herpes herpes simplex infection within 12 weeks prior to inclusion – History of thrombosis or considered at high risk of venous thrombosis by the investigator – Presence of severe JDM-related involvements: cardiovascular (requiring vasopressive drug and/or intensive care unit), respiratory (requiring oxygen and/or intensive care unit), gastrointestinal (requiring abdominal surgery). – History of severe non-related JDM involvement: cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological or neuropsychiatric disorders or any other serious and/or instable illness that, in the opinion of the investigator, could constitute an unacceptable risk, when taking baricitinib. – Actual or in project of pregrancy and breast-feeding until the 7 days after administration of the last dose of Baricitinib – Patient on AME (state medical aid) – Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants

Gender Eligibility: All

Minimum Age: 3 Years

Maximum Age: 18 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Assistance Publique – Hôpitaux de Paris
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Cyril GITIAUX, Doctor, Study Director, Assistance Publique – Hôpitaux de Paris
  • Overall Contact(s)
    • Brigitte BADER-MEUNIER, Doctor, 01 44 49 43 32, brigitte.bader-meunier@aphp.fr

References

Ruperto N, Ravelli A, Pistorio A, Ferriani V, Calvo I, Ganser G, Brunner J, Dannecker G, Silva CA, Stanevicha V, Cate RT, van Suijlekom-Smit LW, Voygioyka O, Fischbach M, Foeldvari I, Hilario O, Modesto C, Saurenmann RK, Sauvain MJ, Scheibel I, Sommelet D, Tambic-Bukovac L, Barcellona R, Brik R, Ehl S, Jovanovic M, Rovensky J, Bagnasco F, Lovell DJ, Martini A; Paediatric Rheumatology International Trials Organisation (PRINTO); Pediatric Rheumatology Collaborative Study Group (PRCSG). The provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/European League Against Rheumatism Disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: a prospective validation study. Arthritis Rheum. 2008 Jan 15;59(1):4-13. doi: 10.1002/art.23248.

Lazarevic D, Pistorio A, Palmisani E, Miettunen P, Ravelli A, Pilkington C, Wulffraat NM, Malattia C, Garay SM, Hofer M, Quartier P, Dolezalova P, Penades IC, Ferriani VP, Ganser G, Kasapcopur O, Melo-Gomes JA, Reed AM, Wierzbowska M, Rider LG, Martini A, Ruperto N; Paediatric Rheumatology International Trials Organisation (PRINTO). The PRINTO criteria for clinically inactive disease in juvenile dermatomyositis. Ann Rheum Dis. 2013 May;72(5):686-93. doi: 10.1136/annrheumdis-2012-201483. Epub 2012 Jun 26.

Bode RK, Klein-Gitelman MS, Miller ML, Lechman TS, Pachman LM. Disease activity score for children with juvenile dermatomyositis: reliability and validity evidence. Arthritis Rheum. 2003 Feb 15;49(1):7-15. doi: 10.1002/art.10924.

Giancane G, Lavarello C, Pistorio A, Oliveira SK, Zulian F, Cuttica R, Fischbach M, Magnusson B, Pastore S, Marini R, Martino S, Pagnier A, Soler C, Stanevicha V, Ten Cate R, Uziel Y, Vojinovic J, Fueri E, Ravelli A, Martini A, Ruperto N; Paediatric Rheumatology International Trials Organisation (PRINTO). The PRINTO evidence-based proposal for glucocorticoids tapering/discontinuation in new onset juvenile dermatomyositis patients. Pediatr Rheumatol Online J. 2019 May 22;17(1):24. doi: 10.1186/s12969-019-0326-5.

Mammen AL, Allenbach Y, Stenzel W, Benveniste O; ENMC 239th Workshop Study Group. 239th ENMC International Workshop: Classification of dermatomyositis, Amsterdam, the Netherlands, 14-16 December 2018. Neuromuscul Disord. 2020 Jan;30(1):70-92. doi: 10.1016/j.nmd.2019.10.005. Epub 2019 Oct 25. No abstract available.

Singh G, Athreya BH, Fries JF, Goldsmith DP. Measurement of health status in children with juvenile rheumatoid arthritis. Arthritis Rheum. 1994 Dec;37(12):1761-9. doi: 10.1002/art.1780371209.

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