Baricitinib in patients with relapsing or naïve dermatomyositis (BIRD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

31 Aug 2022 → ongoing

Decision date (initial)

2024-09-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

French Ministry of Health (PHRC)

External identifiers

EU CT number

2024-511899-32-00

EudraCT number

2020-004987-24

ClinicalTrials.gov

NCT04972760

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

to evaluate the efficacy of baricitinib (JAK1/2 inhibitor) to obtain prednisone-free DM moderate improvement as compared to placebo, in addition to usual care.

Secondary objectives 7

1. Our secondary objectives are to compare between the two groups (baricitinib + usual care versus placebo+ usual care): - the proportion of patients with: minimal improvement (≥ 20 points total improvement ACR/EULAR), moderate improvement (ACR/EULAR≥ 40), major improvement (ACR/EULAR ≥ 60) at W5, W12 and W24.
2. - the primary outcome (prednisone-free moderate improvement) in the following subgroups: DM naive patients vs relapsing/non-naïve; DM with a severe muscle weakness (MMT8 baseline <125/150) vs others
3. - the cutaneous disease activity and damage with a specific DM skin scale (CDASI - Activity and CDASI damages) at W5, W12 and W24
4. - the cumulative incidence of relapse and the time to the first relapse
5. - the cumulative dose of corticosteroids in both groups
6. - the proportions of participants with an average prednisone dose of 0 mg/d, 1-4 mg/d, 5-7.5 mg/d, >7.5 mg/d during weeks 20 through 24.
7. - safety: serious and non-serious adverse events

Conditions and MedDRA coding

Dermatomyositis; Baricitinib in patients with relapsing or naïve dermatomyositis.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. - Adult subjects (≥ 18 years old) < 65 years old
2. - Dermatomyositis (DM) defined according to the 239th ENMC criteria: either naïve or non-naïve DM
3. - Active disease (ACR/EULAR criteria) defined as: • Manual Muscle Testing (MMT-8) <145/150 and at least two additional abnormal corset measurements (CSM): >3/10 cm on Visual Analogue Scale (VAS) of patient global, physician global and extra-muscular disease activity, Health Assessment Questionnaire Disability Index >0.25, or elevated muscle enzymes. • Or cutaneous CDASI > 20 and at least two additional abnormal corset measurements (CSM): >3/10 cm on Visual Analogue Scale (VAS) of patient global, physician global and extra-muscular disease activity, Health Assessment Questionnaire Disability Index >0.25, or elevated muscle enzymes
4. - for relapsing/non naïve DM patients o in case of corticosteroid exposure patient must receive a stable dose < 30 mg/d prednisone with or without additional immunosuppressive therapy for at least 4 weeks before the baseline visit. o Stable dose of immunosuppressive therapy for at least 3 months before
5. - Affiliation to a social security regime
6. - Written informed consent

Exclusion criteria 24

1. - Life-threatening complications o Severe swallowing troubles defined as: food swallowed the wrong way and/or time to drink a glass of 200 ml water above 30 seconds related to DM o Interstitial lung disease related to the DM with one among the following complications (complications must be related to the ILD): dyspnea NYHA III, hypoxemia with PaO2≤65 mmHg, and/or DLCOc/Alveolar Volume ≤70% (pulmonary function test) o Symptomatic myocarditis o Loss of walking ability
2. -Active severe infection including active hepatitis
3. - Evidence of latent tuberculosis (as documented by a positive QuantiFERON-TB Gold plus test)
4. - Absolute Neutrophil Count < 1x109 cells/L
5. - Haemoglobin (Hb) < 8 g/dL
6. - Severe hepatic impairment attested by FV (coagulation factor)<30%
7. - Liver insufficiency (Prothrombin time <60%)
8. - Previous treatment exposure defined as follows: • Rituximab treatment within 6 months before inclusion • IVIg, or cyclophosphamide infusion within the month before inclusion • • both methotrexate (0.3 mg/kg/w) and azathioprine exposure for at least 3 months each and at the 0.3 mg/kg/w and 2-3 mg/kg/d dosages respectively with failure of both (but exposure and/or failure to either of these two drugs alone is not an exclusion criterion) • for naïve DM patients only more than 2 weeks treatment duration with corticosteroids at the dose of 1 mg/kg/d before the inclusion.
9. - Hypersensitivity to the active substance (baricitinib) or to any of the excipients
10. - Contraindication to Methotrexate and/or Azathioprine including hypersensitivity to the active substances or to any of the excipients
11. - Conditions affecting the outcomes (Expected poor compliance)
12. - Patient with deep vein thrombosis/pulmonary embolism or antecedent
13. - Severe disease damages: e.g. muscle weakness mainly related to muscle damage such as fat replacement of muscle) defined as persistent changes in anatomy, physiology, pathology or function which result from previously active disease and from complications of therapy or other events (e.g.; muscle atrophy, fatty replacement; skin scars, poikiloderma). Severe disease damage is considered when the patient condition has no or minor ability to improve with the treatment.
14. -Significant uncontrolled cardiovascular, cerebrovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neuropsychiatric disorders, or abnormal laboratory values that developed during a qualifying study that, in the opinion of the investigator, poses an unacceptable risk for the patient’s participation
15. - Chest imaging (CT scan or radiograph) showing abnormalities not related with the DM in the last 12 weeks judged by the investigator as clinically significant.-Participants included in other intervention research involving humans
16. - Patient under tutorship or guardianship, and incapable to give informed consent
17. - Patient with antecedent of cardiovascular event (myocardial infarction or ischemic stroke)
18. - Patient who is current or past long-time smoker
19. - Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding
20. - No effective contraception during the study and one week after for women of childbearing age
21. - Renal impairment defined as clearance < 60 ml
22. - Strong Organic Anion Transporter 3 (OAT3) inhibitors
23. - Active cancer or history of malignancy
24. -Participants included in other intervention research involving humans

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint: moderate improvement (defined as a total improvement score superior or equal to 40 following ACR/EULAR definition) without corticosteroids at week 24 (prednisone-free moderate improvement).

Secondary endpoints 7

1. -DM improvement at 5, 12 and 24 weeks in terms of: • minimal improvement (≥20 points total improvement ACR/EULAR), • moderate improvement (≥40 points total improvement ACR/EULAR) • major improvement (≥60 points total improvement ACR/EULAR)
2. -Primary endpoint (prednisone-free moderate improvement at W24) in the following subgroups: • DM naive patients at baseline vs others • DM with a severe muscle weakness (MMT8 baseline <125/150) vs others
3. -Cutaneous disease activity and damage evaluated using the CDASI - Activity and CDASI damages at 5, 12 and 24 weeks
4. -Cumulative incidence of relapse and the time to first relapse
5. -Cumulative dose of corticosteroids
6. -Proportions of participants with an average prednisone dose of 0 mg per day, of more than 0 mg to not more than 4.0 mg per day, of more than 4.0 mg to not more than 7.5 mg per day, and of more than 7.5 mg per day during weeks 20 through 24.
7. -Safety including the incidence, nature, and severity of adverse events and serious adverse events and laboratory abnormalities.

Investigational products

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

Test 1

Placebo 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

Yves ALLENBACH

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Yves ALLENBACH

Locations

1 EU/EEA country · 21 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

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