JBT-101 in Systemic Lupus Erythematosus (SLE)

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.