Efficacy of Baricitinib in Relapsing or Naïve Dermatomyositis: A Randomized, Placebo-Controlled Trial

Trial ID: 2024-511899-32-00
Protocol: APHP180612
Sponsor: Assistance Publique Hopitaux De Paris

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Diseases & Conditions

Dermatomyositis

Objectives

The primary objective of this study is to evaluate the **efficacy** of baricitinib, a JAK1/2 inhibitor, in achieving prednisone-free moderate improvement in patients with dermatomyositis (DM) compared to placebo, alongside usual care. This is clinically relevant as it aims to reduce reliance on corticosteroids, which are associated with significant side effects, thereby potentially improving patient outcomes and quality of life.

Secondary objectives include:

Comparing the proportion of patients achieving minimal, moderate, and major improvement (ACR/EULAR criteria) at weeks 5, 12, and 24 between the baricitinib and placebo groups.
Assessing the primary outcome in subgroups of DM naive patients versus relapsing/non-naive, and those with severe muscle weakness (MMT8 baseline <125/150) versus others.
Evaluating cutaneous disease activity and damage using the CDASI scale at weeks 5, 12, and 24.
Determining the cumulative incidence of relapse and time to first relapse.
Measuring the cumulative dose of corticosteroids in both groups.
Analyzing the proportions of participants with varying average prednisone doses during weeks 20 through 24.
Monitoring safety through the occurrence of serious and non-serious adverse events.

Participants

The clinical trial focuses on evaluating the efficacy of **baricitinib** in patients with **dermatomyositis**, specifically targeting those with relapsing or naïve conditions. The study population comprises adult subjects aged 18 to 64 years, including both male and female participants. The trial does not involve a vulnerable population. Participants are required to have active disease as defined by specific criteria, and they must be affiliated with a social security regime. The sponsor has not provided information regarding the total number of participants. The selection criteria include individuals with either naïve or non-naïve dermatomyositis, with specific requirements for those with relapsing conditions, such as stable corticosteroid and immunosuppressive therapy doses prior to the baseline visit. Participants must provide written informed consent to be included in the study. Lifestyle considerations such as diet and physical activity are not specified in the available data.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy of **baricitinib**, a JAK1/2 inhibitor, in achieving prednisone-free moderate improvement in patients with **dermatomyositis** compared to a placebo, alongside usual care. This is a multicenter, double-blind, randomized controlled trial with two parallel groups, conducted with an intention-to-treat analysis. The trial is expected to last until March 31, 2026, with recruitment having commenced on August 31, 2022. Participants will be involved in the study for a maximum treatment period of 24 weeks.

The trial includes a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, disease activity, and treatment history. Eligible participants are adults aged 18 to 65 years with active dermatomyositis, either naïve or non-naïve to treatment. The primary endpoint is a moderate improvement, defined as a total improvement score of 40 or more according to ACR/EULAR criteria, without corticosteroids at week 24. Secondary endpoints include various measures of disease improvement at weeks 5, 12, and 24, as well as safety assessments.

Participants will attend follow-up visits at specified intervals to monitor disease activity, treatment adherence, and any adverse events. The end-of-study visit will occur at the conclusion of the 24-week treatment period, where final assessments will be conducted. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial aims to provide comprehensive data on the efficacy and safety of baricitinib in the treatment of dermatomyositis, contributing valuable insights into potential therapeutic strategies for this condition.

Treatment

The clinical trial involves the administration of **Olumiant** 4 mg film-coated tablets, which contain the active substance **baricitinib**. Baricitinib is a **JAK1/2 inhibitor** and is chemically synthesized. The pharmaceutical form of the medication is a film-coated tablet, and it is administered orally. The maximum daily dose is 4 mg, with a total maximum dose of 672 mg over a treatment period of 24 weeks. The medication is provided by ELI LILLY NEDERLAND B.V. and is identified by the marketing authorization number EU/1/16/1170/009. Participant compliance with the dosing schedule will be monitored throughout the trial.

The study also includes a **placebo** group, which will receive a placebo of Olumiant 4 mg. The placebo is designed to match the experimental medication in appearance and is administered in the same manner, orally, to maintain the blinding of the study. The placebo does not contain any active pharmaceutical ingredients. The use of a placebo allows for the assessment of the efficacy of baricitinib in achieving prednisone-free moderate improvement in patients with **dermatomyositis** when compared to standard care alone.

Efficacy

The efficacy of baricitinib in patients with **Dermatomyositis** will be assessed through a series of predefined endpoints. The primary endpoint is the achievement of a moderate improvement, defined as a total improvement score of 40 or more according to the ACR/EULAR criteria, without the use of corticosteroids at week 24. This is referred to as prednisone-free moderate improvement.

Secondary endpoints include the evaluation of Dermatomyositis improvement at weeks 5, 12, and 24, categorized into minimal improvement (≥20 points), moderate improvement (≥40 points), and major improvement (≥60 points) based on the ACR/EULAR criteria. Additional assessments will focus on subgroups, such as naive patients at baseline and those with severe muscle weakness (MMT8 baseline <125/150). Cutaneous disease activity and damage will be measured using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) at weeks 5, 12, and 24. Other secondary endpoints include the cumulative incidence of relapse, time to first relapse, cumulative corticosteroid dose, and the proportion of participants with varying average prednisone doses during weeks 20 through 24.

Safety will also be monitored, including the incidence, nature, and severity of adverse events, serious adverse events, and laboratory abnormalities. These efficacy parameters will be collected and analyzed at specified timepoints to determine the overall effectiveness of baricitinib in achieving the desired clinical outcomes in patients with Dermatomyositis.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Adult subjects (≥ 18 years old) < 65 years old
Dermatomyositis (DM) defined according to the 239th ENMC criteria: either naïve or non-naïve DM
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
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
Affiliation to a social security regime
Written informed consent

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Exclusion Criteria

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
-Active severe infection including active hepatitis
Evidence of latent tuberculosis (as documented by a positive QuantiFERON-TB Gold plus test)
Absolute Neutrophil Count < 1x109 cells/L
Haemoglobin (Hb) < 8 g/dL
Severe hepatic impairment attested by FV (coagulation factor)<30%
Liver insufficiency (Prothrombin time <60%)
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.
Hypersensitivity to the active substance (baricitinib) or to any of the excipients
Contraindication to Methotrexate and/or Azathioprine including hypersensitivity to the active substances or to any of the excipients
Conditions affecting the outcomes (Expected poor compliance)
Patient with deep vein thrombosis/pulmonary embolism or antecedent
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.
-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
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
Patient under tutorship or guardianship, and incapable to give informed consent
Patient with antecedent of cardiovascular event (myocardial infarction or ischemic stroke)
Patient who is current or past long-time smoker
Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding
No effective contraception during the study and one week after for women of childbearing age
Renal impairment defined as clearance < 60 ml
Strong Organic Anion Transporter 3 (OAT3) inhibitors
Active cancer or history of malignancy
-Participants included in other intervention research involving humans