Trial to Evaluate Efficacy and Safety of Lenabasum in Dermatomyositis

Study Overview
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Brief Summary
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This is a Phase 3 multicenter, double-blind, randomized, placebo-controlled study assessing the efficacy and safety of lenabasum for the treatment of dermatomyositis. Approximately 150 subjects will be enrolled in this study at about 60 sites in North America, Europe, and Asia. The planned duration of double-blind treatment with study drug is up to 52 weeks.

Detailed Description
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Subjects will be randomized to receive lenabasum 20 mg twice per day, lenabasum 5 mg twice per day, or placebo twice per day in a 2:1:2 ratio. The primary efficacy outcome at Week 28 will compare lenabasum 20 mg BID to placebo the Total Improvement Score (TIS), which is a weighted composite measure of improvement from baseline in six endpoints: Physician Global Assessment of Disease Activity, Physician Assessment of Extramuscular Disease Activity, Patient Global Assessment of Disease Activity, Health Assessment Questionnaire (patient-reported disability), Manual Muscle Testing (MMT), and muscle enzymes.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate Efficacy and Safety of Lenabasum in Dermatomyositis

Conditions
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Dermatomyositis

Intervention / Treatment
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* Drug: Lenabasum 20 mg
* Drug: Lenabasum 5 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfill at least one of the following criteria for dermatomyositis: Bohan and Peter criteria (Bohan and Peter, 1975a; Bohan and Peter 1975b) ACR/EULAR criteria (Lundberg et al, 2017) Disease activity/severity fulfills at least one of the following three criteria: MDGA ≥ 3 cm (0 - 10 cm Visual Analog Scale [VAS]) and MMT-8 score ≤ 142 (out of 150 total possible) Sum of MDGA, PtGA and EMGA VAS scores is ≥ 10 cm (0-10 cm VAS for each) MDGA ≥ 3 cm (0-10 cm VAS) and CDASI activity score of > 14 Stable doses of immunosuppressive medications for DM as defined by: Unchanged dose of oral corticosteroids ≤ 20 mg per day prednisone or equivalent for ≥ 4 weeks before Visit 1 Unchanged dose of immunosuppressive medications other than oral corticosteroids for ≥ 8 weeks before Screening Exclusion Criteria: Unstable DM or DM with end-stage organ involvement at Screening or Visit 1 Significant diseases or conditions other than DM that may influence response to the study drug or safety Any of the following values for laboratory tests at Screening: A positive pregnancy test (or at Visit 1) Hemoglobin < 9 g/dL in males and < 8 g/dL in females Neutrophils < 1.0 × 10^9/L Platelets < 75 × 10^9/L Creatinine clearance < 50 mL/min on screening blood test, per the Modification of Diet in Renal Disease Study or in 24 hour urine creatine clearance measurement

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenabasum 20 mg<br>Subjects will receive lenabasum 20 mg twice daily | Drug: Lenabasum 20 mg<br>* oral capsule<br>* Other names: anabasum;|
| Experimental: Lenabasum 5 mg<br>Subjects will receive lenabasum 5 mg twice daily | Drug: Lenabasum 5 mg<br>* oral capsule<br>* Other names: anabasum;|
| Placebo Comparator: Placebo<br>Subjects will receive placebo twice daily | Drug: Placebo<br>* oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of lenabasum 20 mg BID compared to placebo BID as measured by Total Improvement Score (TIS) | TIS from IMAC Core Set Measures (CSM) will be calculated following Aggarwal et al (2017) recommendations. Scores are based on a 0 - 100 scale; higher scores indicate better improvement in myositis. | Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects who achieve Definition of Improvement (DOI) | Defined as ≥ 3 of 6 core set measures improved by ≥ 20% (relative to Baseline) with no more than 2 core set measures worsening by ≥ 25% (MMT-8 may not decrease by ≥ 25% from baseline) | Week 28 | 
| Subjects who improve by at least one category on the Investigator Global Assessment (IGA) scale of skin activity | The IGA is used by the investigator to score overall skin disease on a 0 to 4 scale; higher scores indicate greater skin disease. | Week 28 | 
| Change in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score | CDASI is a validated outcome measure that systematically quantifies cutaneous DM disease activity and damage (Klein et al, 2007; Yassaee et al, 2010) Disease Activity Score is rated using three activity measures. The activity score ranges from 0 to 100. Higher scores indicate greater disease severity. | Week 28 | 
| Subjects who achieve TIS >= 40 (at least moderate improvement) | TIS from IMAC Core Set Measures (CSM) will be calculated following Aggarwal et al (2017) recommendations. Scores are based on a 0 - 100 scale; higher scores indicate better improvement in myositis. | Week 28 | 
| TIS in subjects receiving immunosuppressive therapies (including corticosteroids) for > 1 year at Baseline | TIS from IMAC Core Set Measures (CSM) will be calculated following Aggarwal et al (2017) recommendations. Scores are based on a 0 - 100 scale; higher scores indicate better improvement in myositis. | Week 52 | 
| Change in Forced vital capacity (FVC) absolute, in all subjects and those with interstitial lung disease (ILD) at Baseline. | ILD is defined as a history of fibrosis on chest x-ray, a history of ILD on CT of lungs, and/or FVC% predicted <80% at Screening or Visit 1 | Week 28 | 
| Change in Forced vital capacity (FVC) percent predicted, in all subjects and those with interstitial lung disease (ILD) at Baseline. | ILD is defined as a history of fibrosis on chest x-ray, a history of ILD on CT of lungs, and/or FVC% predicted <80% at Screening or Visit 1 | Week 28 | 
| TIS at Visit 10 | TIS from IMAC Core Set Measures (CSM) will be calculated following Aggarwal et al (2017) recommendations. Scores are based on a 0 - 100 scale; higher scores indicate better improvement in myositis. | Week 52 | 
| TIS, lenabasum 5 mg BID versus placebo | TIS from IMAC Core Set Measures (CSM) will be calculated following Aggarwal et al (2017) recommendations. Scores are based on a 0 - 100 scale; higher scores indicate better improvement in myositis. | Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dermatomyositis, cannabinoid receptor type 2 agonist, JBT-101, lenabasum