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

Phase 2RecruitingNCT05524311

Assistance Publique - Hôpitaux de Paris16 enrolled

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Juvenile Dermatomyositis

Eligibility

Sex: ALLMin age: 3 YearsMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (13)

Hôpital Pellegrin

Bordeaux, France

RECRUITING

Hôpital Femme Mère Enfant

Bron, France

RECRUITING

Hôpital Jeanne de Flandre

Lille, France

RECRUITING

Hôpital La Timone

Marseille, France

RECRUITING

Hôpital Villeneuce

Montpellier, France

NOT_YET_RECRUITING

Hôpital Brabois

Nancy, France

RECRUITING

Hopital Necker - Enfants malades : unité d'immuno-hématologie et rhumatologie

Paris, France

RECRUITING

Hôpital du Kremlin-Bicêtre

Paris, France

RECRUITING

Hôpital Necker - Enfants malades : service de dermatologie

Paris, France

RECRUITING

Hôpital Robert Debré

Paris, France

RECRUITING

...and 3 more locations

Outcomes

Primary Outcomes

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) : 1. muscle strength, assessed with the Childhood Myositis Assessment Scale (CMAS), 2. physician's global assessment of the patient's disease activity (Physician's VAS) 3. global disease activity assessment through the Disease Activity Score (DAS) 4. functional ability through the Childhood Health Assessment Questionnaire (C-HAQ) 5. parent's global assessment of the child's overall wellbeing (Parent's VAS) 6. 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.

Time frame: At week 24

Secondary Outcomes

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

Time frame: At week 4, 8, 12 and 16

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

Time frame: At week 4, 8, 12 and 16

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

Time frame: At week 4, 8, 12 and 16

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

Time frame: At week 4, 8, 12 and 16

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

Time frame: At inclusion, weeks 4, 8, 12, 16 and 24

Clinically inactive disease

according to the PRINTO criteria

Time frame: At weeks 4, 8, 12 and 24

Cutaneous Dermatomyositis Disease Area and Severity Index (CDSAI)

assess skin activity and damage across multiple body regions in patients with dermatomyositis

Time frame: At inclusion, weeks 4, 8, 12, 16 and 24

Myositis Disease Activity Assessment VAS (MYOACT)

Assess Relative and absolute variations of extramuscular activity

Time frame: At inclusion, weeks 4, 8, 12, 16 and 24

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

Time frame: At inclusion and at week 24

Dose of corticosteroid

Dose tapering at 6 months

Time frame: At week 24

Pharmacokinetics study

Non-compartmental analysis of baricitinib

Time frame: At weeks 4, 8, 12, and 24

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

Time frame: At weeks 4, 8, 12, and 24

Pharmacokinetics (PK) study with maximal concentration

Correlation between maximal concentration Cmax in ng/mL (PK parameter of baricitinib) and disease activity 's scores

Time frame: At weeks 4, 8, 12, and 24

Pharmacokinetics (PK) study with through concentration

Correlation between through concentration Ctrough, in ng/mL (PK parameter of baricitinib) and disease activity 's scores

Time frame: At weeks 4, 8, 12, and 24

dosage of cytokines

Measurement of serum IFN -, IFN-γ, IL-1β, IL-4, Il-5, IL-6, IL-8, IL-10, IL-12p70, IL-22, TNF α

Time frame: At inclusion, weeks 4 and 24

transcriptomic analysis

Study of genes expression within 800 genes related to immunity

Time frame: At inclusion, weeks 4 and 24

Biopsy

Assessment of muscle biopsies according to the internationally validated score system

Time frame: At inclusion, weeks 4 and 24

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

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts