Trial to Evaluate Efficacy and Safety of Lenabasum in Diffuse Cutaneous Systemic Sclerosis

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 diffuse cutaneous systemic sclerosis (SSc). Approximately 354 subjects will be enrolled in this study at about 60 sites in North America, Europe, Australia, and Asia. The planned duration of treatment with study drug is 52 weeks.

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

Conditions
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Diffuse Cutaneous Systemic Sclerosis

Intervention / Treatment
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* Drug: Lenabasum 5 mg
* Drug: Lenabasum 20 mg
* Other: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: ≥ 18 years of age at the time Informed Consent is signed. Diffuse cutaneous SSc (skin thickening on upper arms, upper legs, or trunk). Disease duration ≤ 6 years from the first non-Raynaud's symptom. No new or increased doses of immunosuppressive medications within 8 weeks prior to Screening. Key Exclusion Criteria: Unstable SSc or SSc with end-stage organ involvement at Screening or Visit 1. Any of the following values for laboratory tests at Screening: A positive pregnancy test in women of childbearing potential; Hemoglobin < 9 g/dL for males and < 8 g/dL for females; Neutrophils < 1.0 ×10^9/L; Platelets < 75 ×10^9/L; Creatinine clearance < 50 mL/min according to the Modification of Diet in Renal Disease (MDRD) Study equation; Aspartate aminotransferase or alanine aminotransferase > 2.0 × upper limit of normal. Any medical condition or concurrent medical therapies at Screening or Visit 1, including a history of non-compliance with medical treatments, that may put the subject at greater safety risk, influence response to study product, or interfere with study assessments.

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: Cohort 1<br>Lenabasum 5 mg BID | Drug: Lenabasum 5 mg<br>* Subjects will receive lenabasum 5 mg twice daily.<br>|
| Experimental: Cohort 2<br>Lenabasum 20 mg BID | Drug: Lenabasum 20 mg<br>* Subjects will receive lenabasum 20 mg twice daily.<br>|
| Placebo Comparator: Cohort 3<br>Placebo BID | Other: Placebo oral capsule<br>* Subjects will receive placebo twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of lenabasum compared to placebo for the American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis score. | The ACR CRISS exponential algorithm determines the predicted probability of improvement from baseline, incorporating change in mRSS, FVC % predicted, physician and patient global assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A higher score indicates greater improvement. | American College of Rheumatology Combined Response Index score through study completion, up to 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of lenabasum compared to placebo for the change from baseline in modified Rodnan skin score. | mRSS evaluates a subject's skin thickness on a 4 point scale for 17 surface anatomic areas: 0 = normal skin; 1 = mild thickness; 2 = moderate thickness; 3 = severe thickness with inability to pinch skin into fold. The individual values of the 17 surface areas are summed to define the total skin score with a maximum score of 51. | Change from baseline through study completion, up to 1 year. | 
| Efficacy of lenabasum compared to placebo for the change from baseline in Health Assessment Questionnaire - Disability Index. | It includes 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). The individual scores of the eight sections are summed and divided by 8. The result is the disability index or functional disability index. A higher score indicates more functional disability. | Change from baseline through study completion, up to 1 year. | 
| Efficacy of lenabasum compared to placebo for the change from baseline in forced vital capacity. |  | Change from baseline through study completion, up to 1 year. | 

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