MYOCIT - Baricitinib in the treatment of new-onset juvenile dermatomyositis: a phase II trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

10 Nov 2022 → 13 May 2025

Decision date (initial)

2024-09-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-513651-32-00

EudraCT number

2022-000506-10

ClinicalTrials.gov

NCT05524311

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Safety, Efficacy

To assess the efficacy of baricitinib in patients with a new-onset JDM at week 24 according to PRINTO 20 level of improvement

Secondary objectives 13

1. To assess the efficacy of baricitinib in patients with a new onset JDM at weeks 4, 8, 12, 16 according to PRINTO 20 levels of improvement
2. To assess the efficacy of baricitinib in patients with a new onset JDM at weeks 4, 8, 12, 16, 24 according to PRINTO 50, 70, and 90 levels of improvement
3. To determine the response rate to baricitinib at weeks 4, 8, 12, 16, 24 by the Total Improvement Score (TIS) using the 2016 American College of Rheumatology/European League myositis response criteria
4. To assess the efficacy of baracitinib in patients with a new onset JDM at weeks 4, 8, 12, 24 according to the PRINTO criteria of clinically inactive disease.
5. To assess the efficacy of baracitinib on JDM-related-skin disease at weeks 4, 8, 12, 16, 24 according to the cutaneous DM disease area and severity index (CDASI)
6. To assess the efficacy of baracitinib on global disease activity of various extramuscular organ systems according to the Myositis Disease Activity Assessment VAS (MYOACT)
7. To assess the efficacy of baracitinib on interstitial lung disease
8. To assess the safety of baracitinib
9. To assess the reduction in oral corticosteroids at week 24
10. To characterize the pharmacokinetic of baricitinib in children with JDM
11. To assess a correlation between PK and response to baricitinib at week 24
12. To assess the following measures in order to identify biomarkers of JDM activity (at weeks 0, 4 and 24) and biomarkers (V0, V1) predictive of the response to baricitinib at week 24: cytokine circulating levels (IFN -, IFN-γ, IL-1β, IL-4, Il-5, IL-6, IL-8, IL-10, IL-12p70, IL-22, TNF α) independently or jointly (inflammatory score) at inclusion; genes expression within 800 genes related to immunity analyzed at inclusion.
13. To assess a correlation between the muscle biopsy score and the response to baricitinib

Conditions and MedDRA coding

Juvenile Dermatomyositis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patient aged 3-18 years with new-onset juvenile dermatomyositis, according to the ENMC 2018 dermatomyositis classification criteria
2. Muscle weakness at MMT and/or CMAS (MMT < 74 and/or CMAS < 45)
3. Seropositivity or vaccination for chickenpox
4. 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
5. Informed consent form signed by the patient or child’ s parents
6. Patient affiliated to a social security regime

Exclusion criteria 18

1. Amyopathic dermatomyositis (without muscle weakness)
2. Inability to be treated by oral way or to take pills
3. Previous treatment with JAK inhibitor
4. Previous treatment of JDM with immunosuppressive drugs or biologics other than corticosteroids. Previous treatment with prednisone is allowed for no more than 1 month.
5. Previous history of cancer
6. Live vaccine within the 4 weeks before starting baricitinib therapy
7. Current, or recent (< 4 weeks prior to baseline) of active infections, according to investigator appreciation, but necessarily including HBV, HCV, HIV, tuberculosis.
8. Positive blood CMV PCR
9. Creatinine clearance < 40 ml/min
10. Lymphocytes < 0,5x109 cell/L and Neutrophils < 1x109 cell/L
11. Hemoglobin < 8 g/dL
12. Symptomatic herpes herpes simplex infection within 12 weeks prior to inclusion
13. History of thrombosis or considered at high risk of venous thrombosis by the investigator
14. 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).
15. 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.
16. Actual or in project of pregrancy and breast-feeding until the 7 days after administration of the last dose of Baricitinib
17. Patient on AME (state medical aid)
18. Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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)

Secondary endpoints 14

1. The achievement of the PRINTO 20 levels of improvement at weeks 4, 8, 12, 16
2. The achievement of the PRINTO 50, 70 and 90 levels of improvement at weeks 4, 8, 12, 16, 24
3. Relative and absolute variations of TIS between inclusion and weeks 4, 8, 12, 16, 24
4. Clinically inactive disease at weeks 4, 8, 12, 24 according to the PRINTO criteria
5. Relative and absolute variations of CDSAI between inclusion and weeks 4, 8, 12, 16, 24
6. Relative and absolute variations of MYOACT between inclusion and weeks 4, 8, 12, 16, 24
7. Improvement of interstitial lung disease if present at screening: Improvement of pulmonary function tests (improvement of at least 10% of FCV, PTC, and DLCO) and/or improvement of Lung tomodensitomery scored according to a specific scale
8. Adverse events
9. Dose of corticosteroids at week 24
10. Non-compartmental analysis of baricitinib PK
11. Correlation between PK of baricitinib and disease activity ‘s scores
12. Measurement of serum IFN -, IFN-γ, IL-1β, IL-4, Il-5, IL-6, IL-8, IL-10, IL-12p70, IL-22, TNF α at inclusion, weeks 4 and 24.
13. Study of genes expression within 800 genes related to immunity at inclusion, weeks 4 and 24
14. Assessment of muscle biopsies according to the internationally validated score system (Dr Gitiaux)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Brigitte BADER-MEUNIER

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Brigitte BADER-MEUNIER

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications