JBT-101 in Systemic Lupus Erythematosus (SLE)
Condition: Systemic Lupus Erythematosus; SLE; Lupus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: JBT-101; Placebo
Intervention description: Participants will self-administer JBT-101 by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart.; Participants will self-administer JBT-101 placebo by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart.
Intervention MeSH terms: Dronabinol; Lenabasum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 109.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: JBT-101 (also known as lenabasum); efficacy; musculoskeletal disease; randomized trial

Summary:

      The objective of this study is to evaluate the efficacy, safety, and tolerability of JBT-101
      (also known as lenabasum) in systemic lupus erythematosus (SLE).

        -  One hundred adults with active joint disease and at least moderate pain will be enrolled
           in this study to evaluate treatment of their systemic lupus erythematosus (SLE) with
           JBT-101. JBT-101 is a synthetic endocannabinoid receptor type 2 (CB2) agonist and an
           activator of the body's normal processes, to resolve innate immune responses without
           immunosuppression.

        -  Participants will receive 2 doses of JBT-101 by mouth (three groups of varying doses)
           or, placebo, for 84 days and will continue to be followed for an additional 28 days.
           Participant visits to assess endpoints occur on Day 1, then every 2 weeks twice, then
           every 4 weeks three times, for a total of six visits.

        -  The change in maximum daily pain Numerical Rating Scale (NRS) score from Baseline (Visit
           1) will be assessed at every visit.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Fulfills the updated American College of Rheumatology (ACR) 1982 Revised Criteria for
             the Classification of Systemic Lupus Erythematosus;

          -  At least 3 months of treatment with an anti-malarial drug such as hydroxychloroquine
             or a history of intolerance, contraindication, or unwillingness to take an
             anti-malarial drug;

          -  Meets the Safety of Estrogen in Lupus: National Assessment (SELENA) Systemic Lupus
             Erythematosus Disease Activity Index (SLEDAI) definition of arthritis (Petri et al.,
             1999) or mild/moderate arthritis or tendonitis scored as a BILAG B on the updated
             BILAG 2004;

          -  Seven-day average of maximum of daily pain Numerical Rating Scale (NRS) scores ≥ 4 out
             of 10;

          -  Overlap with polymyositis, systemic sclerosis, Sjögren's syndrome, or rheumatoid
             arthritis is allowed, if, in the site investigator's judgment, the predominant
             clinical features are those of Systemic Lupus Erythematosus (SLE);

          -  Not expected by the site investigator to require a change in potential disease-
             modifying treatments for SLE from Screening through Visit 6 (Day 112);

          -  Willing to not start nor stop any Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or
             potential disease-modifying medications or supplements for SLE from Screening through
             Visit 6 (Day 112), unless a change is recommended by the site investigator or other
             treating physicians;

          -  Willing not to use any legal or illegal cannabinoids, including Food and Drug
             Administration (FDA)-approved cannabinoids or cannabinoid-mimic drugs, or any illegal
             substance of abuse from Screening through Visit 6 (Day 112);

          -  If a woman of child-bearing potential, willing to use one of the highly effective
             (failure rate < 1% per year) birth control method from Screening through Visit 6 (Day
             112) or for 28 ± 3 days after the last dose of study product; and

          -  Willing to follow instructions, complete study procedures and attend study visits as
             required by this protocol.

        Exclusion Criteria:

          -  Severe or unstable Systemic lupus erythematosus (SLE), such as any one of the
             following:

               -  A British Isles Lupus Activity Group (BILAG) A score in one or more BILAG domains
                  at Screening;

               -  Treatment with any intraarticular, intravenous, or intramuscular systemic
                  corticosteroids within 14 days of Screening;

               -  Treatment with oral prednisone > 10 mg per day or > 20 mg every other day (or
                  equivalent dose of another corticosteroid) within 14 days of Screening;

               -  Increased dose of systemic corticosteroids in the 14 days prior to Screening;

               -  Treatment with cyclophosphamide or anti-TNFalpha biologic agents within 3 months
                  before Visit 1 (Day 1);

               -  Treatment with B cell-depleting monoclonal antibodies (rituximab, Ocrelizumab,
                  anti-CD22) within 6 months before Visit 1 (Day 1);

               -  Treatment with methotrexate, mycophenolate, azathioprine, leflunomide,
                  cyclosporine, belimumab, tacrolimus, or any other immunosuppressive agent not
                  included in 2b.-d. above, when the dose of that immunosuppressive agent has
                  increased within 3 months before Visit 1. Concurrent treatment with any of these
                  medications is allowed as long as the doses have been stable for at least 3
                  months before Visit 1 (Day 1); or

               -  Actively listed on an organ transplantation list or have received an organ
                  transplant other than a corneal transplant.

          -  Significant diseases or conditions other than SLE that may influence response to the
             study product or safety, such as:

               -  Active bacterial or viral infection requiring systemic antibiotic or anti-viral
                  treatment within 14 days before Visit 1 (Day 1);

               -  Acute or chronic hepatitis B or C infection;

               -  Human immunodeficiency infection (HIV);

               -  History of active tuberculosis or positive tuberculosis skin or blood test
                  without: 1) completing a course of appropriate treatment; or ) having received at
                  least one month of appropriate treatment prior to Visit 1 (Day 1) and continuing
                  to receive appropriate treatment during the study;

               -  No elective surgery should be planned from Visit 1 (Day 1) through Visit 6 (Day
                  112); or

               -  A history of cancer except basal cell carcinoma or in situ carcinoma of the
                  cervix treated with apparent success with curative therapy greater than one year
                  before Visit 1 (Day 1).

               -  Significant heart disease as defined by:

                    -  Uncontrollable congestive heart failure, unstable angina, unstable
                       atherosclerotic cardiovascular disease, significant arrhythmia requiring
                       chronic therapy, pulmonary arterial hypertension with dyspnea, disability
                       rated as New York heart Association Grade III or higher, severe systemic
                       hypertension or severe peripheral vascular disease;

                    -  Marked baseline prolongation of QT/QTc interval (i.e. repeated demonstration
                       of a QTc interval ≥ 450 msec for males and ≥470 msec for females);

                    -  History of risk factors for torsade de pointes (e.g., heart failure,
                       hypokalemia, family history of long QT/QTc syndrome); or

                    -  Clinically significant confirmed abnormality, as determined by the site
                       investigator or qualified designee, on 12-lead Electrocardiogram (ECG) at
                       Screening or Visit 1 (Day 1) before dosing.

          -  History of chronic pain requiring treatment with narcotic analgesia for more than 14
             days total within 6 months of baseline. This does not include self-limited pain
             associated with identifiable events such as surgery;

          -  Current evidence of alcohol abuse (defined as 4 or more drinks per day on at least 4
             days of the week) or history of abuse of illegal and/or legally prescribed drugs such
             as barbiturates, benzodiazepines, amphetamines, cocaine, or opioids during the 1 year
             prior to Screening;

          -  Currently pregnant, breast-feeding, or lactating;

          -  Any investigational agent within 30 days or five therapeutic half-lives of that agent
             whichever is longer, before Visit 1 (Day 1);

          -  Any of the following values for laboratory tests at Screening:

               -  A positive pregnancy test (also at Visit 1);

               -  A newly positive QuantiFERON(R) blood test for tuberculosis, without: 1)
                  completing a course of appropriate treatment; or ) having received at least one
                  month of appropriate treatment prior to Visit 1 and continuing to receive
                  appropriate treatment during the study. If the subject has a previous documented
                  positive tuberculosis skin, then this testing does not need to be repeated. If
                  the subject has a documented negative test result within the last year, testing
                  does not need to be repeated, at the discretion of the site investigator.

               -  Hemoglobin < 8 g/dL;

               -  Neutrophils < 1.0 x 10^9/L;

               -  Platelets < 75 x 10^9/L;

               -  Estimated Glomerular Filtration Rate (eGFR) < 50 ml/min according to
                  Cockcroft-Gault equation;

               -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline
                  phosphatase > 2.0 x upper limit of normal; or

               -  Total bilirubin ≥ 1.5 x upper limit of normal.

          -  Any other conditions that, in the opinion of the site investigator, are clinically
             significant and may put the subject at greater safety risk, influence response to
             study product, or interfere with study assessments. When in doubt, the site
             investigator or qualified designee should discuss the situation with the Protocol
             Chairs.