Clinical trial NCT05524311: Baricitinib in the Treatment of New-onset Juvenile Dermatomyositis (MYOCIT)
Official title: Baricitinib in the Treatment of New-onset Juvenile Dermatomyositis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Juvenile Dermatomyositis
Keywords: juvenile dermatomyositis
baricitinib
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-09-01
Enrollment: 16
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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 \< 0,5x109 cell/L and Neutrophils \< 1x109 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

Primary outcomes:
measure: PRINTO 20 (Paediatric Rheumatology INternational Trials Organisation scale)
timeFrame: At week 24
Secondary outcomes:
measure: PRINTO 20 Paediatric Rheumatology INternational Trials Organisation scale - level 20
timeFrame: At week 4, 8, 12 and 16
measure: PRINTO 50 Paediatric Rheumatology INternational Trials Organisation scale - level 50
timeFrame: At week 4, 8, 12 and 16
measure: PRINTO 70 Paediatric Rheumatology INternational Trials Organisation scale - level 70
timeFrame: At week 4, 8, 12 and 16
measure: PRINTO 90 Paediatric Rheumatology INternational Trials Organisation scale - level 90
timeFrame: At week 4, 8, 12 and 16
measure: Total Improvement Score (TIS)
timeFrame: At inclusion, weeks 4, 8, 12, 16 and 24
measure: Clinically inactive disease
timeFrame: At weeks 4, 8, 12 and 24
measure: Cutaneous Dermatomyositis Disease Area and Severity Index (CDSAI)
timeFrame: At inclusion, weeks 4, 8, 12, 16 and 24
measure: Myositis Disease Activity Assessment VAS (MYOACT)
timeFrame: At inclusion, weeks 4, 8, 12, 16 and 24
measure: interstitial lung disease
timeFrame: At inclusion and at week 24
measure: Dose of corticosteroid
timeFrame: At week 24
measure: Pharmacokinetics study
timeFrame: At weeks 4, 8, 12, and 24
measure: Pharmacokinetics (PK) study with area under the curve
timeFrame: At weeks 4, 8, 12, and 24
measure: Pharmacokinetics (PK) study with maximal concentration
timeFrame: At weeks 4, 8, 12, and 24
measure: Pharmacokinetics (PK) study with through concentration
timeFrame: At weeks 4, 8, 12, and 24
measure: dosage of cytokines
timeFrame: At inclusion, weeks 4 and 24
measure: transcriptomic analysis
timeFrame: At inclusion, weeks 4 and 24
measure: Biopsy
timeFrame: At inclusion, weeks 4 and 24
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: Bron
country: France
facility: Hôpital Femme Mère Enfant
city: Lille
country: France
facility: Hôpital Jeanne de Flandre
city: Marseille
country: France
facility: Hôpital La Timone
city: Montpellier
country: France
facility: Hôpital Villeneuce
city: Nancy
country: France
facility: Hôpital Brabois
city: Paris
country: France
facility: Hopital Necker - Enfants malades : unité d'immuno-hématologie et rhumatologie
city: Paris
country: France
facility: Hôpital du Kremlin-Bicêtre
city: Paris
country: France
facility: Hôpital Necker - Enfants malades : service de dermatologie
city: Paris
country: France
facility: Hôpital Robert Debré
city: Paris
country: France
facility: Hôpital Trousseau
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Toulouse
country: France
facility: Hôpital Purpan
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Cyril GITIAUX, Doctor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.