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

Juvenile Dermatomyositis Clinical Trial

— MYOCIT  

Official title:

Baricitinib in the Treatment of New-onset Juvenile Dermatomyositis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05524311
• Other study ID #: APHP211036
• Secondary ID: 2022-000506-10
• Status: Recruiting
• Phase: Phase 2
• Start date: November 10, 2022
• Est. completion date: September 2026

Study information

• Verified date: December 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Brigitte BADER-MEUNIER, Doctor
• Phone: 01 44 49 43 32
• Email: brigitte.bader-meunier[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: September 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 18 Years

Eligibility

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 ßHCG 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

Related Conditions & MeSH terms

• Dermatomyositis
• Juvenile Dermatomyositis

Intervention

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
• dosage of cytokines
additionnal blood sampling at weeks 0, 4 and 24
• 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
• 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)

Locations

Country	Name	City	State
France	Hôpital Pellegrin	Bordeaux
France	Hôpital Femme Mère Enfant	Bron
France	Hôpital Jeanne de Flandre	Lille
France	Hôpital La Timone	Marseille
France	Hôpital Villeneuce	Montpellier
France	Hôpital Brabois	Nancy
France	Hôpital du Kremlin-Bicêtre	Paris
France	Hôpital Necker - Enfants malades : service de dermatologie	Paris
France	Hopital Necker - Enfants malades : unité d'immuno-hématologie et rhumatologie	Paris
France	Hôpital Robert Debré	Paris
France	Hôpital Trousseau	Paris
France	Hôpital de Hautepierre	Strasbourg
France	Hôpital Purpan	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PRINTO 20 (Paediatric Rheumatology INternational Trials Organisation scale)	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.	At week 24
Secondary	PRINTO 20 Paediatric Rheumatology INternational Trials Organisation scale - level 20	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	At week 4, 8, 12 and 16
Secondary	PRINTO 50 Paediatric Rheumatology INternational Trials Organisation scale - level 50	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	At week 4, 8, 12 and 16
Secondary	PRINTO 70 Paediatric Rheumatology INternational Trials Organisation scale - level 70	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	At week 4, 8, 12 and 16
Secondary	PRINTO 90 Paediatric Rheumatology INternational Trials Organisation scale - level 90	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	At week 4, 8, 12 and 16
Secondary	Total Improvement Score (TIS)	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	At inclusion, weeks 4, 8, 12, 16 and 24
Secondary	Clinically inactive disease	according to the PRINTO criteria	At weeks 4, 8, 12 and 24
Secondary	Cutaneous Dermatomyositis Disease Area and Severity Index (CDSAI)	assess skin activity and damage across multiple body regions in patients with dermatomyositis	At inclusion, weeks 4, 8, 12, 16 and 24
Secondary	Myositis Disease Activity Assessment VAS (MYOACT)	Assess Relative and absolute variations of extramuscular activity	At inclusion, weeks 4, 8, 12, 16 and 24
Secondary	interstitial lung disease	Assessed by improvement of at least 10% of FCV, PTC, and DLCO and/or improvement of Lung tomodensitomery according to a specific scale	At inclusion and at week 24
Secondary	Dose of corticosteroid	Dose tapering at 6 months	At week 24
Secondary	Pharmacokinetics study	Non-compartmental analysis of baricitinib	At weeks 4, 8, 12, and 24
Secondary	Pharmacokinetics (PK) study with area under the curve	Correlation between area under the curve AUC in ng.h/ml (PK parameter of baricitinib) and disease activity 's scores	At weeks 4, 8, 12, and 24
Secondary	Pharmacokinetics (PK) study with maximal concentration	Correlation between maximal concentration Cmax in ng/mL (PK parameter of baricitinib) and disease activity 's scores	At weeks 4, 8, 12, and 24
Secondary	Pharmacokinetics (PK) study with through concentration	Correlation between through concentration Ctrough, in ng/mL (PK parameter of baricitinib) and disease activity 's scores	At weeks 4, 8, 12, and 24
Secondary	dosage of cytokines	Measurement of serum IFN -, IFN-?, IL-1ß, IL-4, Il-5, IL-6, IL-8, IL-10, IL-12p70, IL-22, TNF a	At inclusion, weeks 4 and 24
Secondary	transcriptomic analysis	Study of genes expression within 800 genes related to immunity	At inclusion, weeks 4 and 24
Secondary	Biopsy	Assessment of muscle biopsies according to the internationally validated score system	At inclusion, weeks 4 and 24